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Brentuximab Vedotin and Lenalidomide for Relapsed or Refractory Diffuse Large B-cell Lymphoma

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ClinicalTrials.gov Identifier: NCT02086604
Recruitment Status : Active, not recruiting
First Posted : March 13, 2014
Last Update Posted : June 11, 2019
Sponsor:
Collaborators:
Celgene
Seattle Genetics, Inc.
Information provided by (Responsible Party):
Washington University School of Medicine

Tracking Information
First Submitted Date  ICMJE March 11, 2014
First Posted Date  ICMJE March 13, 2014
Last Update Posted Date June 11, 2019
Actual Study Start Date  ICMJE September 18, 2014
Actual Primary Completion Date June 9, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 30, 2015)
  • Safety as measured by grade and frequency of adverse events [ Time Frame: 30 days after completion of treatment ]
    Adverse events will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
  • Maximum Tolerated Dose (MTD) as measured by the number of dose-limiting toxicities in each dose level (cohort) [ Time Frame: Completion of the first cycle for all participants in dose expansion phase (approximately 12 months) ]
    MTD is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the first cycle. Dose escalations will proceed until the MTD has been reached.
Original Primary Outcome Measures  ICMJE
 (submitted: March 12, 2014)
  • Safety [ Time Frame: 21 days ]
    Hematologic DLT is defined as any of the following that occur during the first cycle that are attributed as possibly, probably, or definitely related to the study treatment:
    • Grade 4 neutropenia > 7 day duration
    • Grade 4 infection with grade 3 or 4 neutropenia (life-threatening sepsis)
    • Grade 4 thrombocytopenia associated with life-threatening bleeding or requiring more than 1 transfusion
    • Treatment delay > 14 days due to hematologic toxicity
    Non-hematologic DLT is defined as any possibly, probably, or definitely related grade 3 or grade 4 non-hematologic toxicity that occurs during the first cycle with the following specific exceptions:
    • Grade 3 or 4 nausea, vomiting, or anorexia that returns to Grade 1 prior to the start of Cycle 2
    • Grade 3 metabolic abnormalities (e.g., hyperglycemia)
  • Maximum Tolerated Dose (MTD) [ Time Frame: 21 days ]
    Hematologic DLT is defined as any of the following that occur during the first cycle that are attributed as possibly, probably, or definitely related to the study treatment:
    • Grade 4 neutropenia > 7 day duration
    • Grade 4 infection with grade 3 or 4 neutropenia (life-threatening sepsis)
    • Grade 4 thrombocytopenia associated with life-threatening bleeding or requiring more than 1 transfusion
    • Treatment delay > 14 days due to hematologic toxicity
    Non-hematologic DLT is defined as any possibly, probably, or definitely related grade 3 or grade 4 non-hematologic toxicity that occurs during the first cycle with the following specific exceptions:
    • Grade 3 or 4 nausea, vomiting, or anorexia that returns to Grade 1 prior to the start of Cycle 2
    • Grade 3 metabolic abnormalities (e.g., hyperglycemia)
Change History Complete list of historical versions of study NCT02086604 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 30, 2015)
  • Objective response rate as measured by CD30 expression [ Time Frame: Up to 2 years after discontinuation of treatment ]
    The objective response rate by CD30 expression (proportion of positive cells, staining intensity, or both) is defined as the proportion of patients with CR or PR stratified by different values or categories of CD30 expression. Positive CD30 expression is defined as ≥1% staining of the malignant cells.
  • Overall response rate [ Time Frame: Up to 2 years after discontinuation of treatment ]
    Complete response rate (CR) + Partial response rate (PR) = Overall response rate according to the Revised Response Criteria for Malignant Lymphoma (Cheson 2007).
  • Duration of response [ Time Frame: Up to 2 years after discontinuation of treatment ]
    Duration of response is defined as the time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of tumor progression (including radiographic and clinical progression) or to death due to any cause, whichever comes first. Duration of response data will be censored on the day following the date of the last disease assessment documenting absence of progressive disease for patients who do not have tumor progression and are still on study at the time of an analysis, are given antitumor treatment (including stem cell transplant) other than the study treatment, or are removed from study prior to documentation of tumor progression. Duration of response will only be calculated for the subgroup of patients achieving a CR or PR.
  • Progression-free survival (PFS) [ Time Frame: Up to 2 years after discontinuation of treatment ]
    PFS is defined as the time from start of study treatment to first documentation of tumor progression (including radiographic and clinical progression) or to death due to any cause, whichever comes first. PFS data will be censored on the day following the date of the last disease assessment documenting absence of progressive disease for patients who do not have tumor progression and are still on study at the time of an analysis, are given antitumor treatment (including stem cell transplant) other than the study treatment, or are removed from study prior to documentation of tumor progression. Patients lacking an evaluation of tumor response after their first dose will have their event time censored at 1 day.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 12, 2014)
  • Association between CD30 expression on tumor cells and clinical efficacy of the combination of brentuximab vedotin and lenalidomide. [ Time Frame: 1 day ]
    Positive CD30 expression is defined as ≥1% staining on the malignant cells
  • Efficacy of BV and lenalidomide in the subsets of activated B cells [ Time Frame: 21 days ]
    Activated B cell-like and germinal center B cell-like DLBCL based on the Hans criteria.
  • Efficacy of brentuximab vedotin and lenalidomide in relapsed/refractory DLBCL [ Time Frame: 3 years ]
    Measured by the overall response rate the proportion of patients with complete remission (CR) or (PR) partial response according to Revised Response Criteria Malignant Lymphoma (Chesin 2007), duration of response defined as the time from start of first documented CR to the first documentation of tumor progression (including radiographic and clinical progression) or death from any cause whichever comes first, and progression free survival (PFS) defined as the time from start of study treatment to first documentation of tumor progression (including radiographic and clinical progression) or death from any cause whichever comes first.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Brentuximab Vedotin and Lenalidomide for Relapsed or Refractory Diffuse Large B-cell Lymphoma
Official Title  ICMJE A Phase I Trial of Brentuximab Vedotin in Combination With Lenalidomide in Relapsed or Refractory Diffuse Large B-cell Lymphoma
Brief Summary This Phase I clinical trial studies the side effects and maximum tolerated dose (MTD) of the combination of brentuximab vedotin (BV) and lenalidomide in the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lymphoma, Large B-Cell, Diffuse
Intervention  ICMJE
  • Drug: Brentuximab vedotin
    Other Name: Adcetris®
  • Drug: Lenalidomide
    Other Name: Revlimid®
Study Arms  ICMJE
  • Experimental: Starting Dose (brentuximab vedotin & lenalidomide)

    Brentuximab vedotin 1.2 mg/kg intravenously (IV) on Day 1 of every 21 day cycle.

    Lenalidomide 20 mg orally on Days 1-21 of every 21 day cycle.

    Interventions:
    • Drug: Brentuximab vedotin
    • Drug: Lenalidomide
  • Experimental: Dose Level 1 (brentuximab vedotin & lenalidomide)

    Brentuximab Vedotin 1.2 mg/kg intravenously (IV) on Day 1 of every 21 day cycle.

    Lenalidomide 20 mg orally on Days 1-21 of every 21 day cycle.

    Interventions:
    • Drug: Brentuximab vedotin
    • Drug: Lenalidomide
  • Experimental: Dose Level 2 (brentuximab vedotin & lenalidomide)

    Brentuximab Vedotin 1.2 mg/kg intravenously (IV) on Day 1 of every 21 day cycle.

    Lenalidomide 20 mg orally on Days 1-21 of every 21 day cycle.

    Interventions:
    • Drug: Brentuximab vedotin
    • Drug: Lenalidomide
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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: August 14, 2017)
37
Original Estimated Enrollment  ICMJE
 (submitted: March 12, 2014)
48
Estimated Study Completion Date  ICMJE November 30, 2019
Actual Primary Completion Date June 9, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Relapsed or refractory de novo or transformed DLBCL disease following at least one prior systemic therapy (for DLBCL).
  • CD30 immunohistochemical staining using the anti-CD30 BerH2 antibody must be available on the most recent biopsy specimen. During dose escalation, patients can be either CD30 positive or CD30 negative. During dose expansion, 15 patients must be CD30 positive and 15 patients must be CD30 negative.
  • Post-ASCT or not a candidate for ASCT. Prior allogeneic stem cell transplant is allowed if patient is off all immunosuppressives and has no evidence of active GVHD.
  • Prior treatment with brentuximab vedotin is allowed provided the patient did not progress on BV or within 30 days of last dose of BV. Patients must be at least 3 months from the last dose of BV.
  • Bidimensional measurable disease of at least 1.5 cm in the greatest transverse diameter as documented by CT or PET/CT.
  • At least 18 years of age.
  • ECOG performance status ≤ 2
  • Bone marrow and organ function as defined below:

    • Absolute neutrophil count (ANC) ≥ 1,000/mcl
    • Platelets ≥ 50,000/mcl
    • Serum bilirubin ≤ 1.5 x institutional upper limit of normal (IULN) OR serum bilirubin ≤ 3.0 x IULN for patients with Gilbert's disease or documented hepatic involvement with NHL
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x IULN OR ALT and AST ≤ 5.0 x IULN for patients with documented hepatic involvement with NHL
    • Creatinine clearance ≥ 60 mL/min/1.73 m2 as calculated by Cockcroft-Gault
  • Women of childbearing potential must follow pregnancy testing requirements as outlined in the Revlimid REMS® program material. This is defined as either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of contraception (one highly effective method and one additional effective method AT THE SAME TIME) at least 28 days prior to the start of lenalidomide, for the duration of study participation, and for 28 days following the last doses of brentuximab vedotin and lenalidomide. Women of childbearing potential must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a woman of childbearing potential even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
  • All study participants must be registered into the mandatory Revlimid REMS® program and be willing to comply with its requirements. Per standard Revlimid REMS® program requirements, all physicians who prescribe lenalidomide for research subjects enrolled into this trial, must be registered in, and must comply with, all requirements of the Revlimid REMS® program.
  • Able to understand and willing to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

  • Primary mediastinal B-cell lymphoma
  • A history of other primary invasive malignancy that has not been in remission for at least 3 years or a current diagnosis of myelodysplastic syndrome (MDS) or an immature leukemia such as acute myeloid leukemia (AML).
  • Known active cerebral/meningeal lymphoma.
  • Present or history of progressive multifocal leukoencephalopathy (PML).
  • NYHA Class III or IV congestive heart failure.
  • Active CTCAE version 4.03 grade 3 or higher viral, bacterial, or fungal infection.
  • Known to be positive for hepatitis B by surface antigen expression and hepatitis B core antibody.
  • Known to have active hepatitis C infection (positive by polymerase chain reaction) or on antiviral therapy for hepatitis C within 6 months prior to the first doses of brentuximab vedotin and lenalidomide.
  • Known to be positive for HIV.
  • Receiving chemotherapy, radiotherapy, biologics, and/or other antitumor treatment with immunotherapy that is not completed at least 3 weeks prior to study entry, unless underlying disease is progressing on therapy.
  • Currently receiving any other investigational agents.
  • Known hypersensitivity to any excipient contained in the drug formulation of brentuximab vedotin or lenalidomide.
  • Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10-14 days prior to and again within 24 hours of starting lenalidomide.
  • Receiving immunosuppressive therapy.
  • Refractory to prior therapy with brentuximab vedotin (evidence of progression within 30 days of the last dose).
  • Prior therapy with lenalidomide.
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 States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02086604
Other Study ID Numbers  ICMJE 201404056
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Washington University School of Medicine
Study Sponsor  ICMJE Washington University School of Medicine
Collaborators  ICMJE
  • Celgene
  • Seattle Genetics, Inc.
Investigators  ICMJE
Principal Investigator: Nancy Bartlett, M.D. Washington University School of Medicine
PRS Account Washington University School of Medicine
Verification Date June 2019

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