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Avelumab In Patients With Previously Treated Advanced Stage Classical Hodgkin's Lymphoma (JAVELIN HODGKINS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02603419
Recruitment Status : Terminated (The study was terminated due to lack of recruitment.)
First Posted : November 11, 2015
Results First Posted : March 18, 2020
Last Update Posted : April 24, 2020
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
This is a Phase 1b, open-label, multi-center study comprising a lead-in phase and an expansion phase. The lead-in phase is a multiple-dose, randomized, parallel-arm, pharmacokinetic and pharmacodynamic study of avelumab as a single agent in adult patients with cHL. Patients enrolled in the lead-in phase of this study are required to have relapsed following a prior autologous or allogeneic HSCT, or to be ineligible for HSCT. Based on the preliminary TO, safety, and efficacy results from the lead-in phase, the expansion phase will evaluate the anti-tumor activity and safety of single-agent avelumab utilizing an intra-patient dose escalation paradigm based on two of the dosing regimens studied in the lead-in phase in 40 cHL patients in whom an allogeneic HSCT has failed.

Condition or disease Intervention/treatment Phase
Hodgkins Lymphoma Drug: Avelumab Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 34 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A PHASE 1 PHARMACOKINETIC-PHARMACODYNAMIC STUDY OF AVELUMAB (MSB0010718C) IN PATIENTS WITH PREVIOUSLY TREATED ADVANCED STAGE CLASSICAL HODGKIN'S LYMPHOMA
Actual Study Start Date : March 10, 2016
Actual Primary Completion Date : December 1, 2018
Actual Study Completion Date : April 11, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Avelumab

Arm Intervention/treatment
Experimental: Lead-in phase-Cohort A
X1 mg IV every 2 weeks
Drug: Avelumab
Anti-PD-L1 antibody at X1 mg IV every 2 weeks to optimize dosing for expansion. Treatment with avelumab will continue until disease progression.

Experimental: Lead-in phase-Cohort B
X2 mg IV every 2 weeks
Drug: Avelumab
Anti-PD-L1 antibody at X2 mg IV every 2 weeks to optimize dosing for expansion. Treatment with avelumab will continue until disease progression.

Experimental: Lead-in phase-Cohort C
X3 mg IV every 3 weeks
Drug: Avelumab
Anti-PD-L1 antibody at X3 mg IV every 3 weeks to optimize dosing for expansion. Treatment with avelumab will continue until disease progression

Experimental: Lead-in phase-Cohort D
X4 mg IV every 2 weeks
Drug: Avelumab
Anti-PD-L1 antibody at X3 mg IV every 2 weeks to optimize dosing for expansion. Treatment with avelumab will continue until disease progression

Experimental: Lead-in phase-Cohort E
X5 mg IV every 2 weeks
Drug: Avelumab
Anti-PD-L1 antibody at X mg IV every 2 weeks. Treatment with avelumab will continue until disease progression

Experimental: Expansion phase
X1 mg IV every 2 weeks followed by X1 or X4 mg every 2 weeks
Drug: Avelumab
Anti-PD-L1 antibody at X1 mg IV every 2 weeks which can be escalated to X4 mg every 2 weeks based on safety and efficacy. Treatment with avelumab will continue until disease progression.




Primary Outcome Measures :
  1. Lead-in Phase: Percent Target Occupancy (CD14+ Monocytes) at Day 2 of Cycle 1 [ Time Frame: Day 2 of Cycle 1 ]
    Target occupancy on peripheral blood CD14+ T-cells by avelumab was investigated in human blood in vitro by flow cytometry.

  2. Lead-in Phase: Percent Target Occupancy (CD14+ Monocytes) at Day 1 of Cycle 2 [ Time Frame: Day 1 of Cycle 2 ]
    Target occupancy on peripheral blood CD14+ T-cells by avelumab was investigated in human blood in vitro by flow cytometry.

  3. Lead-in Phase: Percent Target Occupancy (CD3+ T-Cells) at Day 2 of Cycle 1 [ Time Frame: Day 2 of Cycle 1 ]
    Target occupancy on peripheral blood CD3+ T-cells by avelumab was investigated in human blood in vitro by flow cytometry.

  4. Lead-in Phase: Percent Target Occupancy (CD3+ T-Cells) at Day 1 of Cycle 2 [ Time Frame: Day 1 of Cycle 2 ]
    Target occupancy on peripheral blood CD3+ T-cells by avelumab was investigated in human blood in vitro by flow cytometry.

  5. Expansion Phase: Percentage of Participants With Objective Response as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: From treatment start in expansion phase until progressive disease or death due to any cause (maximum duration of 14 months) ]
    Objective response: complete response (CR) or partial response (PR) according to the Response Criteria for Malignant Lymphoma, from 'start date' until disease progression (Disease progression: >= 20% and >= 5-mm increase in sum of target lesion diameters in reference to smallest sum on study and/or substantial worsening in non-target disease) or death due to any cause. CR was defined as all lymph nodes must have regressed to normal size(less than or equal to 1.5 cm in greatest diameter if >1.5 cm before therapy). Previously involved nodes that were 1.1 to 1.5 cm in greatest diameter must have decreased to less than or equal to 1 cm or by more than 75 percent in sum of products of greatest diameters. PR was defined >= 50% decreased in the sum of products of the greatest diameters (SPD) of 6 largest dominant nodes or nodal masses. No increase in size of nodes, liver or spleen and no new sites of disease. Splenic and hepatic nodules must regress by >=50% in the SPD.

  6. Lead-in Phase: Area Under the Plasma Concentration-Time Profile From Time Zero to Extrapolated Infinity (AUC0-inf) of Avelumab After Single Dose [ Time Frame: pre-dose, 1, 6, 24, 144, and 312 hours post-dose on Day 1 of Cycle 1 ]
    AUC(0-inf) was defined as area under the plasma concentration-time profile from time zero to extrapolated infinity AUC(0-inf), after single dose.

  7. Lead-in Phase: Area Under the Plasma Concentration-Time Profile From Time Zero to Extrapolated Infinity (AUC0-inf) of Avelumab After Multiple Dose [ Time Frame: pre-dose, 1, 6, 24, 144, 312, 336 and 504 hours post-dose on Day 1 of Cycle 2 ]
    AUC(0-inf) was defined as area under the plasma concentration-time profile from time zero to extrapolated infinity AUC(0-inf), after multiple dose.

  8. Lead-in Phase: Maximum Observed Plasma Concentration (Cmax) of Avelumab After Single Dose [ Time Frame: pre-dose, 1, 6, 24, 144, and 312 hours post-dose on Day 1 of Cycle 1 ]
  9. Lead-in Phase: Maximum Observed Plasma Concentration (Cmax) of Avelumab After Multiple Dose [ Time Frame: pre-dose, 1, 6, 24, 144, and 312 hours post-dose on Day 1 of Cycle 2 ]
  10. Lead-in Phase: Area Under the Plasma Concentration-Time Profile From Time Zero (Pre-Dose) to the Next Dose (AUC0-tau) of Avelumab After Single Dose [ Time Frame: pre-dose, 1, 6, 24, 144, and 312 hours post-dose on Day 1 of Cycle 1 ]
    AUCtau was defined as area under the plasma concentration-time profile from time zero (pre-dose) to the next dose (AUC0-tau) of avelumab, after single dose.

  11. Lead-in Phase: Area Under the Plasma Concentration-Time Profile From Time Zero (Pre-Dose) to the Next Dose (AUC0-tau) of Avelumab After Multiple Dose [ Time Frame: pre-dose, 1, 6, 24, 144, and 312 hours post-dose on Day 1 of Cycle 2 ]
    AUCtau was defined as area under the plasma concentration-time profile from time zero (pre-dose) to the next dose (AUC0-tau) of avelumab, after multiple dose.

  12. Lead-in Phase: Terminal Elimination Half-Life (t1/2) of Avelumab After Single Dose [ Time Frame: pre-dose, 1, 6, 24, 144, and 312 hours post-dose on Day 1 of Cycle 1 ]
    Terminal elimination half-life is the time measured for the plasma concentration to decrease by one half of avelumab, after single dose.

  13. Lead-in Phase: Terminal Elimination Half-Life (t1/2) of Avelumab After Multiple Dose [ Time Frame: pre-dose, 1, 6, 24, 144, and 312 hours post-dose on Day 1 of Cycle 2 ]
    Terminal elimination half-life is the time measured for the plasma concentration to decrease by one half of avelumab, after multiple dose.

  14. Lead-in Phase: Time to Attain Maximum Observed Plasma Concentration (Tmax) of Avelumab After Single Dose [ Time Frame: pre-dose, 1, 6, 24, 144, and 312 hours post-dose on Day 1 of Cycle 1 ]
    Time to reach maximum observed plasma concentration of avelumab, after single dose.

  15. Lead-in Phase: Time to Attain Maximum Observed Plasma Concentration (Tmax) of Avelumab After Multiple Dose [ Time Frame: pre-dose, 1, 6, 24, 144, and 312 hours post-dose on Day 1 of Cycle 2 ]
    Time to reach maximum observed plasma concentration of avelumab, after multiple dose.

  16. Lead-in Phase: Pre-Dose Concentration During Multiple Dosing (Ctrough) of Avelumab After Multiple Dose [ Time Frame: pre-dose, 1, 6, 24, 144, and 312 hours post-dose on Day 1 of Cycle 2 ]
  17. Lead-in Phase: The Last Time Point of the Last Quantifiable Concentration (Tlast) of Avelumab After Single Dose [ Time Frame: pre-dose, 1, 6, 24, 144, 312 and 527 hours post-dose on Day 1 of Cycle 1 ]
    The last time point of the last quantifiable concentration (Tlast) of avelumab, after single dose.

  18. Lead-in Phase: The Last Time Point of the Last Quantifiable Concentration (Tlast) of Avelumab After Multiple Dose [ Time Frame: pre-dose, 1, 6, 24, 144, 312, 336 and 504 hours post-dose on Day 1 of Cycle 2 ]
    The last time point of the last quantifiable concentration (tlast) of avelumab, after multiple dose.


Secondary Outcome Measures :
  1. Lead-in Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Related TEAEs and TEAEs Graded >=3 as Per National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 [ Time Frame: From first dose of study drug to 90 days after last administration of study drug (maximum duration of 32 months) ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03: Grade 3: severe or medically significant but not immediately life-threatening, or prolongation of existing hospitalization indicated; Grade 4: life-threatening consequence; Grade 5: death related to AE. SAE was an AE resulting in any of following outcomes: death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or congenital anomaly. A TEAEs: an event that emerged during treatment period (From first dose of study drug until end of open label phase [From first dose of study drug to 90 days after last administration of study drug (maximum duration of 32 months)] that was absent before treatment,or worsened during treatment period relative to pre-treatment state. AE was considered related to study drug if event was assessed by investigator as probably or possibly related.

  2. Lead-in Phase: Number of Participants With Laboratory Abnormalities Graded Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 [ Time Frame: From first dose of study drug up to 90 days after the last administration of the study drug (maximum duration of 32 months) ]
    Hematology: Anemia (Grade)G3: Hg <8.0 grams/deciliter (g/dL); lymphocyte count decreased G3: <0.5-0.2*10^9/L, G4: <0.2*10^9/L; neutrophil count decreased: G3: <1.0-0.5*10^9/L, G4: <0.5*10^9/L; platelet count decreased: G3:<50.0-25.0*10^9/L, G4: <25.0*10^9/L; white blood cell (WBC) decreased: G3: <0.2*10^9/L, G4: <1.0*10^9/L. Chemistry: [ALT, ALP increased and AST G3: >5.0-20.0*ULN, G4: >20.0*ULN]. blood bilirubin increased: G3: >3.0-10.0*ULN, G4: >10.0 *ULN. [cholesterol high: G3: >10.34 - 12.92, G4: >12.92; hypokalemia G3: <3.0-2.5, G4: <2.5]mmol/L, creatine phosphokinase (Cpk) increased: G3: >5*ULN-10*ULN, G4: >10*ULN; gamma-glutamyl transferase (Ggt) increased: G3: >5.0-20.0*ULN, G4: >20.0*ULN; [hypertriglyceridemia G3: >500-1000, G4: >1000; hypermagnesemia, G3: >3.0-8.0, G 4: >8.0]mg/dL, Lipase increased: G3: >2.0 - 5.0*ULN, G4: >5.0*ULN, Serum amylase increased: G3: >2.0 - 5.0*ULN, G4: >5.0*ULN. Only those category in which at least one participant had data were reported.

  3. Lead-in Phase: Number of Participants With Anti-Drug Antibodies (ADA) Status [ Time Frame: Day 1 up to Month 29 ]
    ADA against avelumab in serum samples was determined and reported separately for ADA never-positive and ADA ever-positive participants. ADA never-positive participants were those who had no positive (titer less than cutpoint [22.5 percentage (%) inhibition]) ADA results at any time point. ADA ever-positive participants were defined as those who had at least one positive (titer greater than or equal to cutpoint [22.5% inhibition]) ADA result at any time point.

  4. Expansion Phase: Number of Participants With Anti-Drug Antibodies (ADA) Status [ Time Frame: Day 1 up to Month 14 ]
    ADA against avelumab in serum samples was determined and reported separately for ADA never-positive and ADA ever-positive participants. ADA never-positive participants were those who had no positive (titer less than cutpoint [22.5% inhibition]) ADA results at any time point. ADA ever-positive participants were defined as those who had at least one positive (titer greater than or equal to cutpoint [22.5% inhibition]) ADA result at any time point.

  5. Lead-in Phase: Number of Participants With Neutralizing Antibodies (nAb) Status [ Time Frame: Day 1 up to Month 29 ]
    nAb against avelumab in serum samples was determined and reported separately for nAb never-positive and nAb ever-positive participants. nAb never-positive participants were those who had no positive (titer less than cutpoint [0.71]) nAb results at any time point. nAb ever-positive participants were defined as those who had at least one positive (titer greater than or equal to cutpoint [0.71]) nAb result at any time point.

  6. Expansion Phase: Number of Participants With Neutralizing Antibodies (nAb) Status [ Time Frame: Day 1 up to Month 14 ]
    nAb against avelumab in serum samples was determined and reported separately for nAb never-positive and nAb ever-positive participants. nAb never-positive participants were those who had no positive (titer less than cutpoint [0.71]) nAb results at any time point. nAb ever-positive participants were defined as those who had at least one positive (titer greater than or equal to cutpoint [0.71]) nAb result at any time point.

  7. Lead-in Phase: Number of ADA Ever Positive Participants For Each Serum ADA Titers for Avelumab [ Time Frame: Day 1 up to Month 29 ]
    Serum samples were assayed for ADA using a validated analytical method. Number of ADA ever positive participants for each serum ADA titer (180, 4860, 43740 and 131220) are reported.

  8. Expansion Phase: Number of ADA Ever Positive Participants For Each Serum ADA Titers for Avelumab [ Time Frame: Day 1 up to Month 14 ]
    Serum samples were assayed for ADA using a validated analytical method. Number of ADA ever positive participants for each serum ADA titer (180, 4860, 43740 and 131220) are reported.

  9. Lead-in Phase: Number of nAb Ever Positive Participants For Serum nAb Titer for Avelumab [ Time Frame: Day 1 up to Month 29 ]
    Serum samples were assayed for nAb using a validated analytical method. Number of nAb ever positive participants for serum nAb titer (1) is reported.

  10. Expansion Phase: Number of nAb Ever Positive Participants For Serum nAb Titer for Avelumab [ Time Frame: Day 1 up to Month 14 ]
    Serum samples were assayed for nAb using a validated analytical method.

  11. Lead-in Phase: Number of Participants With Phenotype of Tumor Infiltrating Lymphocytes (TILs) in Tumor Biopsy [ Time Frame: Day 1 (pre-dose) and Day 14 of Cycle 1, Day 7 of Cycle 2, Day 1 (pre-dose) of Cycle 3, 5, 7; and at End of Treatment (EOT) (maximum duration of 29 months) ]
  12. Lead-in Phase: Number of Participants With Gene Expression of Transcripts Associated With Immune Activation and Regulation [ Time Frame: Day 1 (pre-dose) and Day 14 of Cycle 1, Day 7 of Cycle 2, Day 1 (pre-dose) of Cycle 3, 5, 7; and at End of Treatment (maximum duration of 29 months) ]
  13. Lead-in Phase: Number of Participants With T Cell Immunophenotype [ Time Frame: Day 1 of Cycles 1, 2, 3, 4, 7, 10 and at End of Treatment (maximum duration of 29 months) ]
  14. Lead-in Phase: Percentage of Participants With Objective Response as Assessed by Investigator [ Time Frame: From randomization until disease progression or death due to any cause (maximum duration of 32 months) ]
    Objective response: complete response (CR) or partial response (PR) according to the Response Criteria for Malignant Lymphoma, from 'start date' until disease progression (Disease progression: >= 20% and >= 5-mm increase in sum of target lesion diameters in reference to smallest sum on study and/or substantial worsening in non-target disease) or death due to any cause. CR was defined as all lymph nodes must have regressed to normal size(less than or equal to 1.5 cm in greatest diameter if >1.5 cm before therapy). Previously involved nodes that were 1.1 to 1.5 cm in greatest diameter must have decreased to less than or equal to 1 cm or by more than 75 percent in sum of products of greatest diameters. PR was defined >= 50% decreased in the SPD of 6 largest dominant nodes or nodal masses. No increase in size of nodes, liver or spleen and no new sites of disease. Splenic and hepatic nodules must regress by >=50% in the SPD.

  15. Lead-in Phase: Percentage of Participants With Disease Control (DC) as Assessed by Investigator [ Time Frame: From randomization to PD, death or start of new anti-cancer therapy (maximum duration of 32 months) ]
    DC: best overall response of CR, PR, or stable disease (SD). CR was defined as all lymph nodes must have regressed to normal size(less than or equal to 1.5 cm in greatest diameter if >1.5 cm before therapy). Previously involved nodes that were 1.1 to 1.5 cm in greatest diameter must have decreased to less than or equal to 1 cm or by more than 75% in sum of the products of greatest diameters. PR was defined >=50% decreased in SPD of 6 largest dominant nodes or nodal masses. No increase in size of nodes, liver or spleen and no new sites of disease. Splenic and hepatic nodules must regress by >=50% in SPD and SD was defined as < PR but not progressive disease. To qualify as a best overall response of SD, at least one SD assessment must be observed >=6 weeks after start date and before disease progression. (Disease progression: >= 20% and >= 5-mm increase in sum of target lesion diameters in reference to smallest sum on study and/or substantial worsening in non-target disease).

  16. Lead-in Phase: Time to Tumor Response (TTR) as Assessed by Investigator [ Time Frame: From the date of randomization to the first documentation of objective response (CR or PR) (maximum duration of 32 months) ]
    TTR was defined, for participants with an objective response as the time from 'start date' to the first documentation of objective tumor response (CR or PR). CR was defined as all lymph nodes must have regressed to normal size(less than or equal to 1.5 cm in greatest diameter if >1.5 cm before therapy). Previously involved nodes that were 1.1 to 1.5 cm in greatest diameter must have decreased to less than or equal to 1 cm or by more than 75 percent in the sum of the products of the greatest diameters. PR was defined >=50% decreased in the SPD of 6 largest dominant nodes or nodal masses. No increase in size of nodes, liver or spleen and no new sites of disease. Splenic and hepatic nodules must regress by >=50% in the SPD.

  17. Lead-in Phase: Duration of Response (DR) as Assessed by Investigator [ Time Frame: From first documentation of objective response to date of first documentation of objective PD or death due to any cause (maximum duration of 32 months) ]
    DR is defined, for participants with an objective response, as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of objective PD or to death due to any cause, whichever occurs first. CR was defined as all lymph nodes must have regressed to normal size(less than or equal to 1.5 cm in greatest diameter if >1.5 cm before therapy). Previously involved nodes that were 1.1 to 1.5 cm in greatest diameter must have decreased to less than or equal to 1 cm or by more than 75 percent in the sum of the products of the greatest diameters. PR was defined >=50% decreased in the SPD of 6 largest dominant nodes or nodal masses. No increase in size of nodes, liver or spleen and no new sites of disease. Splenic and hepatic nodules must regress by >=50% in the SPD.(PD: >= 20% and >= 5-mm increase in sum of target lesion diameters in reference to smallest sum on study and/or substantial worsening in non-target disease).

  18. Lead-in Phase: Progression-Free Survival (PFS) as Assessed by Investigator [ Time Frame: From randomization to the date of progression of disease or death due to any cause, whichever occurs first (maximum duration of 32 months) ]
    PFS was defined as time (in months) from date of randomization to the first documentation of disease progression or death (due to any cause), whichever occurred first. Progression as per RECIST 1.1, was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered as progression of disease.

  19. Expansion Phase: Percentage of Participants With Objective Response as Assessed by Investigator [ Time Frame: From treatment start in expansion phase until disease progression or death due to any cause (maximum duration of 14 months) ]
    Objective response was defined as CR or PR according to the Response Criteria for Malignant Lymphoma, from 'start date' until disease progression or death due to any cause. CR was defined as all lymph nodes must have regressed to normal size(less than or equal to 1.5 cm in greatest diameter if >1.5 cm before therapy). Previously involved nodes that were 1.1 to 1.5 cm in greatest diameter must have decreased to less than or equal to 1 cm or by more than 75 percent in the sum of the products of the greatest diameters. PR was defined >=50% decreased in the SPD of 6 largest dominant nodes or nodal masses. No increase in size of nodes, liver or spleen and no new sites of disease. Splenic and hepatic nodules must regress by >=50% in the SPD. (PD: >= 20% and >= 5-mm increase in sum of target lesion diameters in reference to smallest sum on study and/or substantial worsening in non-target disease).

  20. Expansion Phase: Time to Tumor Response (TTR) as Assessed by Investigator and by Blinded Independent Central Review (BICR) [ Time Frame: From treatment start in expansion phase to first documentation of objective response (CR or PR) (maximum duration of 14 months) ]
    Time to Tumor Response (TTR) was defined, for participants with an objective response as the time from 'start date' to the first documentation of objective tumor response (CR or PR). CR was defined as all lymph nodes must have regressed to normal size(less than or equal to 1.5 cm in greatest diameter if >1.5 cm before therapy). Previously involved nodes that were 1.1 to 1.5 cm in greatest diameter must have decreased to less than or equal to 1 cm or by more than 75 percent in the sum of the products of the greatest diameters. PR was defined >=50% decreased in the sum of products of the greatest diameters (SPD) of 6 largest dominant nodes or nodal masses. No increase in size of nodes, liver or spleen and no new sites of disease. Splenic and hepatic nodules must regress by >=50% in the SPD.

  21. Expansion Phase: Duration of Response (DR) as Assessed by Investigator and by Blinded Independent Central Review (BICR) [ Time Frame: From first documentation of objective response in expansion phase to date of first documentation of objective PD or death due to any cause (maximum duration of 14 months) ]
    Duration of Response (DR) is defined, for participants with an objective response, as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of objective progression of disease (PD) or to death due to any cause, whichever occurs first. CR was defined as all lymph nodes must have regressed to normal size(less than or equal to 1.5 cm in greatest diameter if >1.5 cm before therapy). Previously involved nodes that were 1.1 to 1.5 cm in greatest diameter must have decreased to less than or equal to 1 cm or by more than 75 percent in the sum of the products of the greatest diameters. PR was defined >=50% decreased in the sum of products of the greatest diameters (SPD) of 6 largest dominant nodes or nodal masses. No increase in size of nodes, liver or spleen and no new sites of disease. Splenic and hepatic nodules must regress by >=50% in the SPD.

  22. Expansion Phase: Percentage of Participants With Disease Control (DC) as Assessed by Investigator and by Blinded Independent Central Review (BICR) [ Time Frame: From treatment start in expansion phase to PD, death or start of new anti-cancer therapy (maximum duration of 14 months) ]
    Disease Control (DC) was defined as the best overall response of CR, PR, or SD. CR was defined as all lymph nodes must have regressed to normal size(less than or equal to 1.5 cm in greatest diameter if >1.5 cm before therapy). Previously involved nodes that were 1.1 to 1.5 cm in greatest diameter must have decreased to less than or equal to 1 cm or by more than 75 percent in the sum of the products of the greatest diameters. PR was defined >=50% decreased in the sum of products of the greatest diameters (SPD) of 6 largest dominant nodes or nodal masses. No increase in size of nodes, liver or spleen and no new sites of disease. Splenic and hepatic nodules must regress by >=50% in the SPD and Stable Disease was defined as less than a PR but not progressive disease. To qualify as a best overall response of SD, at least one SD assessment must be observed >=6 weeks after start date and before disease progression.

  23. Expansion Phase: Progression-Free Survival (PFS) as Assessed by Investigator and by Blinded Independent Central Review (BICR) [ Time Frame: From treatment start in expansion phase to date of first documentation of objective Progressive Disease (PD) or death due to any cause, whichever occurs first (maximum duration of 14 months) ]
    PFS was defined as time (in months) from date of randomization to the first documentation of disease progression or death (due to any cause), whichever occurred first. Progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. Analysis was performed using a Cox's Proportional Hazard model stratified by the randomization strata and a stratified log-rank test.

  24. Expansion Phase: Overall Survival [ Time Frame: From treatment start in expansion phase until death (maximum duration of 14 months) ]
    Overall survival was defined as the time (in months) from the date of randomization to the date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan-Meier method.

  25. Expansion Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Related TEAEs and TEAEs Graded >=3 Based on, National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 [ Time Frame: From first dose of study drug to 90 days after last administration of study drug (maximum duration of 14 months) ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03: Grade 3: severe or medically significant but not immediately life-threatening, or prolongation of existing hospitalization indicated; Grade 4: life-threatening consequence; Grade 5: death related to AE. SAE was an AE resulting in any of following outcomes: death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or congenital anomaly. TEAEs: an event that emerged during treatment period (From first dose of study drug until end of expansion phase [From first dose of study drug to 90 days after last administration of study drug (maximum duration of 14 months)] that was absent before treatment, or worsened during treatment period relative to pre-treatment state. AE was considered related to study drug if event was assessed by investigator as probably or possibly related.

  26. Expansion Phase: Number of Participants With Laboratory Abnormalities of Grade 3 Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 [ Time Frame: From first dose of study drug to 90 days after last administration of study drug (maximum duration of 14 months) ]
    As per NCI-CTCAE v 4.03, Grade >= 3 criteria were; Alanine aminotransferase: 0 LLN, 0.58 ULN microkat/L (microkatal /L); GGT: 0 LLN, 0.63 ULN microkat/L, Glucose: 4.11 LLN, 5.88 ULN mmol/L, LOW Sodium: 136 LLN, 146 ULN mmol/L; Prothrombin intl. normalized ratio: 0.9 LLN, 1.2 ULN; LOW lymphocytes (10^9/L); 1.5 LLN, 4.0 ULN; Platelets (10^9/L): 130 LLN, 400 ULN. Only those category in which at least one participant had data were reported.

  27. Expansion Phase: Number of Participants With Acute and Chronic Graft Versus Host Disease (GVHD) [ Time Frame: From treatment start in expansion phase up to 90 days after last administration of study drug (maximum duration of 14 months) ]
    Acute GvHD is a reaction of donor immune cells against host tissues. The three main tissues that acute GvHD affects are the skin, liver and gastrointestinal tract. Chronic GvHD is a syndrome of variable clinical features resembling autoimmune and other immunologic disorders. Manifestations of chronic GvHD may be restricted to a single organ or site or may be widespread, with profound impact on quality of life.

  28. Expansion Phase: Area Under the Plasma Concentration-Time Profile From Time Zero to Extrapolated Infinity (AUC0-inf), After Single and Multiple Dose [ Time Frame: pre-dose and 1 hour post-dose on Day 1 of Cycles 1, 2 and 3 ]
    AUC(0-inf) was defined as area under the plasma concentration-time profile from time zero to infinity AUC(0-inf), after single and multiple dose.

  29. Expansion Phase: Maximum Observed Plasma Concentration (Cmax) of Avelumab After Single and Multiple Dose [ Time Frame: pre-dose and 1 hour post-dose on Day 1 of Cycles 1, 2 and 3 ]
  30. Expansion Phase: Area Under the Plasma Concentration-Time Profile From Time Zero (Pre-Dose) to the Next Dose (AUC0-tau) of Avelumab, After Single and Multiple Dose [ Time Frame: pre-dose and 1 hour post-dose on Day 1 of Cycles 1, 2 and 3 ]
    AUCtau was defined as area under the plasma concentration-time profile from time zero (pre-dose) to the next dose (AUC0-tau) of avelumab, after single and multiple dose.

  31. Expansion Phase: Terminal Elimination Half-Life (t1/2) of Avelumab After Single and Multiple Dose [ Time Frame: pre-dose and 1 hour post-dose on Day 1 of Cycles 1, 2 and 3 ]
    Terminal elimination half-life is the time measured for the plasma concentration to decrease by one half.

  32. Expansion Phase: Time to Attain Maximum Observed Plasma Concentration (Tmax) of Avelumab After Single and Multiple Dose [ Time Frame: pre-dose and 1 hour post-dose on Day 1 of Cycles 1, 2 and 3 ]
  33. Expansion Phase: Pre-Dose Concentration During Multiple Dosing (Ctrough) of Avelumab After Single and Multiple Dose [ Time Frame: pre-dose and 1 hour post-dose on Day 1 of Cycles 1, 2 and 3 ]
  34. Expansion Phase: The Last Time Point of the Last Quantifiable Concentration (Tlast) of Avelumab After Single and Multiple Dose [ Time Frame: pre-dose and 1 hour post-dose on Day 1 of Cycles 1, 2 and 3 ]
    The last time point of the last quantifiable concentration (tlast), after single and multiple dose.

  35. Expansion Phase: Number of Participants With Phenotype of Tumor Infiltrating Lymphocytes (TILs) in Tumor Biopsy [ Time Frame: Pre-treatment tumor biopsy for baseline and on-treatment biopsy at Day 7 of Cycle 3 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

KEY INCLUSION CRITERIA

  • Histological confirmation of classical Hodgkin's Lymphoma (cHL) with relapsed or refractory disease who, for the lead-in phase, either have had a prior autologous or allogeneic HSCT or are not eligible for HSCT, and , for the expansion phase, have had a prior allogeneic HSCT. In the expansion phase there must be a documented CD3+ donor chimerism of ≥20%.
  • Patients must be off previous cHL therapy for at least 28 days prior to randomization in the lead-in phase/first dose of study treatment in the expansion phase.
  • At least 1 fluorodeoxyglucose (FDG) PET avid (Deauville 4/5) measurable lesion >1.5 cm on PET-CT scan as defined by the Response Criteria for Malignant Lymphoma (for the lead-in phase) and the Lugano Classification (for the expansion phase) that has not previously been irradiated.
  • Expansion phase: Required "de novo" or "archival" tumor biopsy, as well as required on treatment biopsy
  • Estern Cooperative Oncology Group (ECOG) Performance Status 0 or 1

KEY EXCLUSION CRITERIA

  • Patients with prior allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) who have had:

    1. Lead-in phase: allo HSCT performed <12 months prior to randomization. Expansion phase: allo-HSCT performed ≤4 months prior to the first dose of study treatment. NOTE: Patients who have had allo-HSCT performed >4 months prior to the first dose of study treatment must have discontinued all immunosuppressive therapy, and must have no clinical evidence of GVHD; or
    2. Immunosuppressive treatment for acute or chronic GVHD within 3 months prior to randomization for the lead-in phase or prior to the first dose of study treatment for the expansion phase (with the exception of those patients who required 15 mg/day oral prednisone or equivalent). Patients who required 15 mg/day oral prednisone or equivalent must have discontinued it within 7 days prior to first dose of study treatment; or
    3. Acute Grade 3 or Grade 4 GVHD at any time in the past (as defined by the modified Seattle Glucksberg criteria (Consensus Conference on Acute GVHD Grading Criteria); or
    4. Prior chronic GVHD (as defined by the NIH Consensus Development Project) that persisted for >6 months and required systemic immunosuppression (with the exception of those patients who required 15 mg/day oral prednisone or equivalent). Patients who required 15 mg/day oral prednisone or equivalent must have discontinued it within 7 days prior to the first dose of study treatment; or
    5. A donor lymphocyte infusion (DLI) within 3 months prior to randomization for the lead-in phase or first dose of study treatment for the expansion phase.
  • Prior therapy with an anti PD 1 or anti PD L1 mAb.

    1. Lead-in Phase: May be enrolled if patient stopped prior anti PD1 or anti-PD-L1 therapy more than one year prior to randomization and had a documented prior response.
    2. Expansion Phase: Prior therapy with an anti-PD-1 or anti-PD-L1 agent following allo-HSCT is prohibited unless the therapy was stopped more than one year prior to the first dose of study treatment, and the patient had a documented prior response. NOTE: Prior therapy with an anti-PD-1 or anti-PD-L1 agent prior to allo-HSCT is permitted with no time limits and irrespective of a documented response.
    3. Patients with a history of ≥Grade 3 anti-PD-1 or anti-PD-L1-related immune toxicity are not eligible.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02603419


Locations
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United States, California
City of Hope
Duarte, California, United States, 91010
Italy
Az. Ospedaliera-Univers. di Bologna Policlinico S.Orsola-Malpighi
Bologna, BO, Italy, 40138
Istituto Clinico Humanitas U.O. Oncologia ed Ematologia
Rozzano, Milano, Italy, 20089
United Kingdom
Q2 Solutions
Rosebank, Livingston, United Kingdom, EH54 7EG
Oxford University Hospitals NHS Foundation Trust
Headington, United Kingdom, OX3 7LE
Leeds Teaching Hospital NHS Trust
Leeds, United Kingdom, LS9 7TF
St James's University Hospital
Leeds, United Kingdom, LS97TF
University Hospitals of Leicester NHS Trust
Leicester, United Kingdom, LE1 5WW
University Hospitals of Leicester NHS Trust
Leicester, United Kingdom, LE2 7LG
University College London Hospitals NHS Foundation Trust
London, United Kingdom, N7 9NH
UCLH Clinical Research Facility
London, United Kingdom, WIT 7HA
The Christie NHS Foundation Trust
Manchester, United Kingdom, M20 4BX
Plymouth Hospitals NHS Trust, Derriford Hospital
Plymouth, United Kingdom, PL6 8DH
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
  Study Documents (Full-Text)

Documents provided by Pfizer:
Study Protocol  [PDF] November 13, 2017
Statistical Analysis Plan  [PDF] April 9, 2018

Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02603419    
Other Study ID Numbers: B9991007
2015-002636-41 ( EudraCT Number )
JAVELIN HODGKINS ( Other Identifier: Alias Study Number )
JAVELIN HODGKIN'S ( Other Identifier: Alias Study Number )
First Posted: November 11, 2015    Key Record Dates
Results First Posted: March 18, 2020
Last Update Posted: April 24, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Keywords provided by Pfizer:
classical Hodgkins Lymphoma (relapsed/refractory)
post-allogeneic HSCT
anti PD-L1
Phase 1
PK
Receptor occupancy
Immunophenotypic biomarkers
Additional relevant MeSH terms:
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Lymphoma
Hodgkin Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs