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Trial record 1 of 1 for:    Study NCT02432235
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Study of ADCT-301 in Patients With Relapsed or Refractory Hodgkin and Non-Hodgkin Lymphoma

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ClinicalTrials.gov Identifier: NCT02432235
Recruitment Status : Completed
First Posted : May 4, 2015
Last Update Posted : March 11, 2020
Sponsor:
Information provided by (Responsible Party):
ADC Therapeutics S.A.

Tracking Information
First Submitted Date  ICMJE February 26, 2015
First Posted Date  ICMJE May 4, 2015
Last Update Posted Date March 11, 2020
Study Start Date  ICMJE June 2015
Actual Primary Completion Date October 24, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 11, 2016)
Assessment of Dose Limiting Toxicities in Determination of the Maximum Tolerated Dose [ Time Frame: The protocol-defined assessment period is 1 21-day cycle ]
Dose Limiting toxicities as defined per protocol, as related to ADCT-301
Original Primary Outcome Measures  ICMJE
 (submitted: April 28, 2015)
Assessment of Dose Limiting Toxicities in Determination of the Maximum Tolerated Dose [ Time Frame: The protocol-defined assessment period is 1 28-day cycle ]
Dose Limiting toxicities as defined per protocol, as related to ADCT-301
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 11, 2016)
  • Overall Response Rate, Duration of Response, Progression Free Survival, and Overall Survival (composite endpoint) [ Time Frame: Disease assessments will occur within 6 days prior to Day 1 of Cycles 3 and 5 and thereafter every third cycle until progression of disease or initiation of a new anticancer therapy for up to 12 months. ]
    Date of disease progression will be defined as the earliest date of radiological disease progression as assessed by the investigator using the 2014 Lugano Classification for response for Hodgkin and Non-Hodgkin Lymphoma or Global Response Score criteria for disease progression
  • Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199 [ Time Frame: Blood sample collection on Day 1, 8 and 15 of 21-day cycles 1 and 2. ]
    Noncompartmental analysis of the maximum concentration (Cmax)
  • Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199 [ Time Frame: Blood sample collection on Day 1, 8 and 15 of 21-day cycles 1 and 2. ]
    Noncompartmental analysis of the time to maximum concentration (Tmax)
  • Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199 [ Time Frame: Blood sample collection on Day 1, 8 and 15 of 21-day cycles 1 and 2. ]
    Noncompartmental analysis of the area under the concentration-time curve from time zero to the last quantifiable concentration (AUC0 last)
  • Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199 [ Time Frame: Blood sample collection on Day 1, 8 and 15 of 21-day cycles 1 and 2. ]
    Noncompartmental analysis of the area under the concentration-time curve from time zero to the end of the dosing interval (AUC0-τ)
  • Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199 [ Time Frame: Blood sample collection on Day 1, 8 and 15 of 21-day cycles 1 and 2. ]
    Noncompartmental analysis of the area under the concentration-time curve from time zero to infinity (AUC0-∞)
  • Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199 [ Time Frame: Blood sample collection on Day 1, 8 and 15 of 21-day cycles 1 and 2. ]
    Noncompartmental analysis of the accumulation index (AI)
  • Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199 [ Time Frame: Blood sample collection on Day 1, 8 and 15 of 21-day cycles 1 and 2. ]
    Noncompartmental analysis of the volume of distribution at a steady-state (Vss)
  • Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199 [ Time Frame: Blood sample collection on Day 1, 8 and 15 of 21-day cycles 1 and 2. ]
    Noncompartmental analysis of the mean residence time (MRT)
  • Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199 [ Time Frame: Blood sample collection on Day 1, 8 and 15 of 21-day cycles 1 and 2. ]
    Noncompartmental analysis of the terminal elimination phase rate constant (λz)
  • Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199 [ Time Frame: Blood sample collection on Day 1, 8 and 15 of 21-day cycles 1 and 2. ]
    Noncompartmental analysis of T1/2
  • Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199 [ Time Frame: Blood sample collection on Day 1, 8 and 15 of 21-day cycles 1 and 2. ]
    Noncompartmental analysis of CL
  • Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199 [ Time Frame: Blood sample collection on Day 1, 8 and 15 of 21-day cycles 1 and 2. ]
    Noncompartmental analysis of Vz
  • Evaluation of anti-drug antibodies (ADAs) in blood before, during, and after treatment with ADCT 301 [ Time Frame: Blood sample collection on Day 1 of each 21 day cycle ]
    Expressed as either negative or positive titer expressed as a dilution factor
Original Secondary Outcome Measures  ICMJE
 (submitted: April 28, 2015)
  • Overall Response Rate, Duration of Response, Progression Free Survival, and Overall Survival (composite endpoint) [ Time Frame: Disease assessments will occur every other cycle for the first 2 evaluations (at 6 and 12 weeks) and every third cycle (every 9 wks) thereafter from randomization until progression of disease or initiation of a new anticancer therapy for up to 12 months. ]
    Date of disease progression will be defined as the earliest date of radiological disease progression as assessed by the investigator using the 2014 Lugano Classification for response for Hodgkin and Non-Hodgkin Lymphoma or modified Severity-Weighted Assessment Tool (mSWAT) criteria for disease progression
  • Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199 [ Time Frame: Blood sample collection on Day 1, 8 and 15 of 28-day cycles 1 and 2. ]
    Noncompartmental analysis of the maximum concentration (Cmax)
  • Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199 [ Time Frame: Blood sample collection on Day 1, 8 and 15 of 28-day cycles 1 and 2. ]
    Noncompartmental analysis of the time to maximum concentration (Tmax)
  • Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199 [ Time Frame: Blood sample collection on Day 1, 8 and 15 of 28-day cycles 1 and 2. ]
    Noncompartmental analysis of the area under the concentration-time curve from time zero to the last quantifiable concentration (AUC0 last)
  • Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199 [ Time Frame: Blood sample collection on Day 1, 8 and 15 of 28-day cycles 1 and 2. ]
    Noncompartmental analysis of the area under the concentration-time curve from time zero to the end of the dosing interval (AUC0-τ)
  • Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199 [ Time Frame: Blood sample collection on Day 1, 8 and 15 of 28-day cycles 1 and 2. ]
    Noncompartmental analysis of the area under the concentration-time curve from time zero to infinity (AUC0-∞)
  • Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199 [ Time Frame: Blood sample collection on Day 1, 8 and 15 of 28-day cycles 1 and 2. ]
    Noncompartmental analysis of the accumulation index (AI)
  • Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199 [ Time Frame: Blood sample collection on Day 1, 8 and 15 of 28-day cycles 1 and 2. ]
    Noncompartmental analysis of the volume of distribution at a steady-state (Vss)
  • Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199 [ Time Frame: Blood sample collection on Day 1, 8 and 15 of 28-day cycles 1 and 2. ]
    Noncompartmental analysis of the mean residence time (MRT)
  • Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199 [ Time Frame: Blood sample collection on Day 1, 8 and 15 of 28-day cycles 1 and 2. ]
    Noncompartmental analysis of the terminal elimination phase rate constant (λz)
  • Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199 [ Time Frame: Blood sample collection on Day 1, 8 and 15 of 28-day cycles 1 and 2. ]
    Noncompartmental analysis of T1/2
  • Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199 [ Time Frame: Blood sample collection on Day 1, 8 and 15 of 28-day cycles 1 and 2. ]
    Noncompartmental analysis of CL
  • Pharmacokinetics and Pharmacodynamics assessment - Total Antibody Hu-Max-TAC, pyrrolobenzodiazepine (PBD) conjugated HuMax-TAC and free warhead SG3199 [ Time Frame: Blood sample collection on Day 1, 8 and 15 of 28-day cycles 1 and 2. ]
    Noncompartmental analysis of Vz
  • Evaluation of anti-drug antibodies (ADAs) in blood before, during, and after treatment with ADCT 301 [ Time Frame: Blood sample collection on Day 1 of each 28 day cycle ]
    Expressed as either negative or positive titer expressed as a dilution factor
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of ADCT-301 in Patients With Relapsed or Refractory Hodgkin and Non-Hodgkin Lymphoma
Official Title  ICMJE A Phase 1 Adaptive Dose-Escalation Study to Evaluate the Tolerability, Safety, Pharmacokinetics, and Antitumor Activity of ADCT-301 in Patients With Relapsed or Refractory Hodgkin Lymphoma and Non-Hodgkin Lymphoma
Brief Summary

This study evaluates ADCT-301 in patients with relapsed/refractory Non-Hodgkin or Hodgkin lymphoma. Patients will participate in a dose-escalation phase (Part 1) and receive escalating doses of ADCT-301 every 3 weeks.

In Part 2 of the study, patients will receive a recommended dose(s) of ADCT-301 every 3 weeks.

Detailed Description

This is a Phase I, first in human clinical study with ADCT-301 to evaluate the safety and tolerability and pharmacokinetics of ADCT-301 in patients with relapsed/refractory lymphoma.

ADCT-301 is a human monoclonal antibody attached via a cleavable linker to a pyrrolobenzodiazepine (PBD) warhead which, when internalized by antigen expressing cells, covalently cross links deoxyribonucleic acid (DNA) preventing replication.

The study will be conducted in 2 parts: In part 1 (dose escalation) up to 80 patients will receive an infusion of ADCT-301 on Day 1, every 3 weeks. Dose escalation will continue until the maximum tolerated dose (MTD) is determined.

In Part 2 (expansion) up to 60 patients will be assigned to receive the recommended dose(s) of ADCT-301 as determined by a Dose Escalation Steering Committee.

For each patient, the study will include a screening period (up to 28 days), a treatment period, and a follow-up period to assess disease progression and survival for up to 12 months after the last dose of study drug. The total study duration will be dependent on overall patient tolerability to the study drug and response to treatment. It is anticipated that the entire study (Parts 1 and 2) could last approximately 3 years from first patient treated to last patient completed.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hodgkin Lymphoma
  • Non-Hodgkin Lymphoma
  • Burkitt's Lymphoma
  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Follicular
  • Lymphoma, Mantle-Cell
  • Lymphoma, Marginal Zone
  • Waldenstrom's Macroglobulinaemia
  • Lymphoma,T-cell Cutaneous
  • Lymphoma, T-Cell, Peripheral
Intervention  ICMJE Drug: ADCT-301
intravenous infusion
Other Name: Camidanlumab tesirine
Study Arms  ICMJE Experimental: ADCT-301

In Part 1 (dose-escalation), patients will receive a 1-hour intravenous infusion of ADCT-301 on Day 1 every 3 weeks (21-day cycle). Dose escalation will be conducted according to a continual reassessment method.

In Part 2 (expansion), patients will be assigned to receive the recommended dose(s) of ADCT-301 as determined by the Dose Escalation Steering Committee (DESC).

Intervention: Drug: ADCT-301
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 8, 2019)
133
Original Estimated Enrollment  ICMJE
 (submitted: April 28, 2015)
90
Actual Study Completion Date  ICMJE October 24, 2019
Actual Primary Completion Date October 24, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female age 18 years or older.
  2. Refractory or relapsed lymphoma (per World Health Organization (WHO) Classification system)
  3. Pathologically confirmed relapsed or refractory lymphoma
  4. Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block.
  5. Measurable disease, defined by the 2014 Lugano Classification Criteria
  6. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
  7. Absolute neutrophil count ≥1500/µL.
  8. Platelet count of ≥75000/µL.
  9. Hemoglobin ≥9.0 g/dL without transfusion within the 2 weeks prior to Day 1.
  10. Creatinine ≤1.5mg/dL
  11. Serum alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase ≤2 times the upper limit of normal (ULN); ≤ 5 times ULN if there is liver or bone involvement.
  12. Total serum bilirubin ≤1.5 times ULN
  13. Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin pregnancy test within 7 days prior to Day 1.
  14. Women of childbearing potential must agree to use a highly effective method of contraception. Men with female partners who are of childbearing potential must agree that they or their partners will use a highly effective method of contraception.

Exclusion Criteria:

  1. Patients who have an option for any treatment with proven clinical benefit for their lymphoid malignancy at current state of disease.
  2. Active graft-versus-host disease.
  3. Autologous or allogenic transplant within the 60 days prior to Cycle 1 Day 1.
  4. Evidence of myelodysplasia or myeloid leukemia by morphology, immunostains, flow cytometry, or cytogenetics on a bone marrow aspirate or biopsy.
  5. Known history of positive serum human anti-drug antibody (ADA), or known allergy to any component of ADCT-301
  6. History of symptomatic autoimmune disease
  7. Known seropositive for human immunodeficiency (HIV) virus, hepatitis B surface antigen (HbsAg), or antibody to hepatitis C virus (anti-HCV)
  8. History of Steven's Johnson's syndrome or toxic epidermal necrolysis syndrome.
  9. Pregnant or breastfeeding women.
  10. Significant medical comorbidities, including uncontrolled hypertension (diastolic blood pressure greater than 115 mm Hg), unstable angina, congestive heart failure (greater than New York Heart Association class II), severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia, poorly controlled diabetes, severe chronic pulmonary disease, coronary angioplasty, or myocardial infarction within 6 months prior to screening, or uncontrolled atrial or ventricular cardiac arrhythmias.
  11. Use of any other experimental medication(s) within 14 days prior to start of the study treatment.
  12. Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy (including prednisone ≥ 40 mg/day or equivalent) within 14 days or 5 half-lives (whichever is shorter) prior to Cycle 1, Day 1 treatment.
  13. Failure to recover (to Common Terminology Criteria for Adverse Events [CTCAE Version 4.0] Grade 0 or Grade 1) from acute non-hematologic toxicity (except alopecia or Grade 2 or lower neuropathy), due to previous therapy, prior to Screening.
  14. Congenital long QT syndrome or a corrected QTc interval ≥ 470 ms at screening
  15. Active second primary malignancy other than non-melanoma skin cancers, nonmetastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy
  16. Any other significant medical illness, abnormality, or condition
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02432235
Other Study ID Numbers  ICMJE ADCT-301-001
2015-005272-25 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party ADC Therapeutics S.A.
Study Sponsor  ICMJE ADC Therapeutics S.A.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account ADC Therapeutics S.A.
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP