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Trial record 1 of 1 for:    NCT02603419
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Avelumab In Patients With Previously Treated Advanced Stage Classical Hodgkin's Lymphoma (JAVELIN HODGKINS)

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ClinicalTrials.gov Identifier: NCT02603419
Recruitment Status : Terminated (The study was terminated due to lack of recruitment.)
First Posted : November 11, 2015
Last Update Posted : July 16, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE November 9, 2015
First Posted Date  ICMJE November 11, 2015
Last Update Posted Date July 16, 2019
Actual Study Start Date  ICMJE March 10, 2016
Actual Primary Completion Date December 1, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 11, 2017)
  • Lead-in phase: Percent Receptor Occupancy (TO) [ Time Frame: Days 1, 2, 7, and 14 of cycles 1 and 2, Day 1 (predose) of Cycles 3 and 4 and at End of Treatment. (Cycle = either 14 or 21 days) ]
    Percent TO by dose/schedule in peripheral blood CD14+ monocytes and CD3+ T cells.
  • Lead-in phase: Maximum Observed Plasma Concentration (Cmax) of avelumab [ Time Frame: Hour 0 (pre-dose), 1, 6, 24 (Day 2), 144 (Day 7), and 312 (Day 14) hours post dose of cycles 1 and 2. Pre-dose on Day 1 of Cycles 3, 4, 6, 8 and every 12 weeks, up to Cycle 20. (Cycle = either 14 or 21 days) ]
    Cmax defined as the maximum plasma concentration of avelumab (MSB0010718C)
  • Lead-in phase: Area Under the Curve (AUC) of avelumab [ Time Frame: Hour 0 (pre-dose), 1, 6, 24 (Day 2), 48 (Day 3), 144 (Day 7), and 312 (Day 14) hours post dose of Cycles 1 and 2. Pre-dose on Day 1 of Cycles 3, 4, 6, 8 and every 12 weeks, up to Cycle 20. (Cycle = either 14 or 21 days) ]
    AUC defined as the Area Under the Curve during the dosing interval of avelumab (MSB0010718C)
  • Expansion phase: Objective response [ Time Frame: From treatment start until progressive disease or death due to any cause ]
    Number of participants with objectiver response (CR or PR) as evaluated by the blinded independent central review (BICR)
Original Primary Outcome Measures  ICMJE
 (submitted: November 10, 2015)
  • Percent Receptor Occupancy (TO) [ Time Frame: Days 1, 2, 7, and 14 of cycles 1 and 2, Day 1 (predose) of Cycles 3 and 4 and through study completion, up to approximately 24 months. (Cycle = either 14 or 21 days) ]
    Percent TO by dose/schedule in peripheral blood CD14+ monocytes and CD3+ T cells.
  • Maximum Observed Plasma Concentration (Cmax) of avelumab [ Time Frame: Hour 0 (pre-dose), 1, 6, 24 (Day 2), 48 (Day 3), 144 (Day 7), and 312 (Day 14) hours post dose. Pre-dose on Day 1 of Cycles 3, 4, 6, 8 and every 12 weeks through study completion, up to approximately 24 months. (Cycle = either 14 or 21 days) ]
    Cmax defined as the maximum plasma concentration of avelumab (MSB0010718C)
  • Area Under the Curve (AUC) of avelumab [ Time Frame: Hour 0 (pre-dose), 1, 6, 24 (Day 2), 48 (Day 3), 144 (Day 7), and 312 (Day 14) hours post dose. Pre-dose on Day 1 of Cycles 3, 4, 6, 8 and every 12 weeks through study completion, up to approximately 24 months. (Cycle = either 14 or 21 days) ]
    AUC defined as the Area Under the Curve from time zero to last quantifiable concentration of avelumab (MSB0010718C)
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) of avelumab [ Time Frame: Hour 0 (pre-dose), 1, 6, 24 (Day 2), 48 (Day 3), 144 (Day 7), and 312 (Day 14) hours post dose. Pre-dose on Day 1 of Cycles 3, 4, 6, 8 and every 12 weeks through study completion, up to approximately 24 months. (Cycle = either 14 or 21 days) ]
    Tmax defined as the time to reach maximum plasma concentration of avelumab (MSB0010718C)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 11, 2017)
  • Lead-in phase: Anti-Drug Antibody (ADA) levels of avelumab (MSB0010718C) [ Time Frame: Day 1 (pre-dose) of Cycles 1, 2, 3, 4, 6, and 8 and every 12 weeks, up to Cycle 20 (Cycle = either 14 or 21 days) ]
    Immunogenicity assessment of avelumab (MSB0010718C).
  • Lead-in phase: Phenotype of tumor infiltrating lymphocytes (TILs) in tumor biopsy [ Time Frame: Pre-treatment tumor biopsy (or archival FFPE) for baseline and on-treatment biopsy at Day 28 ]
    Phenotype, quantity, and localization of TILs in tumor biopsy tissue by immunohistochemistry.
  • Lead-in phase: Gene expression of transcripts associated with immune activation and regulation [ Time Frame: Pre-treatment tumor biopsy (or archival FFPE) for baseline and on-treatment biopsy at Day 28 ]
    Relative expression of transcripts associated with immune activation and regulation in tumor biopsy tissue by gene expression profiling
  • Lead-in phase: T cell immunophenotype [ Time Frame: Day 1 (pre dose) of Cycle 1; and Day 1 of Cycles 2, 3, 4, 7, 10 and at End of Treatment (Cycle = either 14 or 21 days) ]
    Phenotype, relative proportions, activation state and PD-L1 expression of peripheral blood T cell subsets.
  • Lead-in phase/Expansion phase: Objective Response (OR) [ Time Frame: From randomization/treatment start until disease progression or death due to any cause ]
    Number of participants with objective response (CR or PR) by Investigator's assessment.
  • Lead-in phase/Expansion phase: Time to Tumor Response (TTR) [ Time Frame: From the date of randomization/treatment start to the first documentation of objective response (CR or PR) ]
  • Lead-in phase/Expansion phase: Duration of Response (DR) [ Time Frame: From first documentation of objective response (CR or PR) to the date of first documentation of objective progression of disease (PD) or death due to any cause ]
  • Lead-in phase/Expansion phase: Progression Free Survival (PFS) [ Time Frame: PFS is defined as the time from randomization/treatment start to the date of the first documentation of objective Progressive Disease (PD) or death due to any cause, whichever occurs first ]
  • Lead-in phase/Expansion phase: Disease control [ Time Frame: From randomization/treatment start to PD, death or start of new anti-cancer therapy ]
  • Lead-in phase/Expansion phase: Laboratory abnormalities [ Time Frame: From screening up to 90 days after the last administration of the study drug ]
    As characterized by type, severity (as graded by NCI CTCAE v 4.03) and timing.
  • Lead-in/Expansion phase: Adverse Events and laboratory abnormalities [ Time Frame: From randomization/treatment start to 90 days after the last administration of the study drug ]
    As graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.4.03
  • Expansion phase: Acute and Chronic GVHD [ Time Frame: From treatment start up to 90 days after the last administratio of the study drug ]
    Acute GVHD as defined by the modified Seattle Glucksberg criteria and chronic GVHD, as defined by the NIH Consensus Development Project
  • Expansion phase: Anti-Drug Antibody (ADA) levels against avelumab [ Time Frame: Day 1 (pre-dose) of Cycles 1, 2, 3, 4, 7 and 13 and at the end of Treatment/Withdrawal ]
    Immunogenicity assessment of avelumab
  • Expansion phase: Phenotype of tumor infiltrating lymphocytes (TILs) in tumor biopsy [ Time Frame: Pre-treatment tumor biopsy (or archival FFPE) for baseline and on-treatment biopsy at Day 7 of Cycle 3 ]
    Phenotype, quantity, and localization of TILs in tumor biopsy tissue by immunohistochemistry.
  • Expansion phase: Maximum Observed Plasma Concentration (Cmax) of avelumab [ Time Frame: Hour 0 (pre-dose) and 1 hour post-dose on Day 1 of Cycles 1, 2 and 3. 144 hours post-dose (Day 7) of Cycles 1 and 2. Hour 0 (pre-dose) on Day 1 of Cycles 4,7 and 13. ]
    Cmax is defined as the maximum plasma concentration of avelumab
  • Expansion phase: Area under the curve (AUC) of avelumab [ Time Frame: Hour 0 (pre-dose) and 1 hour post-dose on Day 1 of Cycles 1, 2 and 3. 144 hours post-dose (Day 7) of Cycles 1 and 2. Hour 0 (pre-dose) on Day 1 of Cycles 4,7 and 13. ]
    AUC is defined as the area the curve during the dosing interval.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 10, 2015)
  • Anti-Drug Antibody (ADA) levels of avelumab (MSB0010718C) [ Time Frame: Pre-dose on Day 1 of Cycles 1, 2, 3, 4, 6, and 8 and every 12 weeks through study completion, up to approximately 24 months (Cycle = either 14 or 21 days) ]
    Immunogenicity assessment of avelumab (MSB0010718C).
  • Phenotype of tumor infiltrating lymphocytes (TILs) in tumor biopsy [ Time Frame: Pre-treatment tumor biopsy (or archival FFPE) for baseline and on-treatment biopsy at Day 28 ]
    Phenotype, quantity, and localization of TILs in tumor biopsy tissue by immunohistochemistry.
  • Gene expression of transcripts associated with immune activation and regulation [ Time Frame: Pre-treatment tumor biopsy (or archival FFPE) for baseline and on-treatment biopsy at Day 28 ]
    Relative expression of transcripts associated with immune activation and regulation in tumor biopsy tissue by gene expression profiling
  • T cell immunophenotype [ Time Frame: Day 1 (pre dose) of Cycle 1, Day 1 of Cycles 2, 3, 4, 7, 10 and through study completion, up to approximately 24 months (Cycle = either 14 or 21 days) ]
    Phenotype, relative proportions, activation state and PD-L1 expression of peripheral blood T cell subsets.
  • Objective Response (OR) [ Time Frame: Baseline up to approximately 24 months ]
    Number of participants with OR (ie, confirmed complete or partial response according to Response Criteria for Malignant Lymphoma).
  • Time to Tumor Response (TTR) [ Time Frame: Baseline up to approximately 24 months ]
    TTR is defined for patients with confirmed objective response as the time from the date of first dose of study treatment to the first documentation of objective tumor response.
  • Duration of Response (DR) [ Time Frame: Baseline up to approximately 24 months ]
    DR is defined for patients with confirmed objective response as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.
  • Progression Free Survival (PFS) [ Time Frame: Baseline up to approximately 24 months ]
    PFS is defined as the time from the date of first dose of study treatment to the date of disease progression by Response Criteria for Malignant Lymphoma or death due to any cause, whichever occurs first.
  • Immune cell phenotyping [ Time Frame: Day 1 (pre dose) of Cycle 1, Day 1 of Cycles 2, 3, 4, 7, 10 and through study completion, up to approximately 24 months (Cycle = either 14 or 21 days) ]
    Immune cell phenotypes associated with anti-tumor immunity and immune regulation
  • Soluble receptor [ Time Frame: Day 1 (pre-dose) and end of infusion, Day 2 of Cycle 1 and Day 1 of Cycles 2, 3, 4, 7, 10 and through study completion, up to approximately 24 months (Cycle = either 14 or 21 days) ]
    Soluble factors associated with immune activation, regulation and potential pharmacodynamic activity.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Avelumab In Patients With Previously Treated Advanced Stage Classical Hodgkin's Lymphoma (JAVELIN HODGKINS)
Official Title  ICMJE A PHASE 1 PHARMACOKINETIC-PHARMACODYNAMIC STUDY OF AVELUMAB (MSB0010718C) IN PATIENTS WITH PREVIOUSLY TREATED ADVANCED STAGE CLASSICAL HODGKIN'S LYMPHOMA
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hodgkins Lymphoma
Intervention  ICMJE
  • 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.
  • 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.
  • 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
  • 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
  • Drug: Avelumab
    Anti-PD-L1 antibody at X mg IV every 2 weeks. Treatment with avelumab will continue until disease progression
  • 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.
Study Arms  ICMJE
  • Experimental: Lead-in phase-Cohort A
    X1 mg IV every 2 weeks
    Intervention: Drug: Avelumab
  • Experimental: Lead-in phase-Cohort B
    X2 mg IV every 2 weeks
    Intervention: Drug: Avelumab
  • Experimental: Lead-in phase-Cohort C
    X3 mg IV every 3 weeks
    Intervention: Drug: Avelumab
  • Experimental: Lead-in phase-Cohort D
    X4 mg IV every 2 weeks
    Intervention: Drug: Avelumab
  • Experimental: Lead-in phase-Cohort E
    X5 mg IV every 2 weeks
    Intervention: Drug: Avelumab
  • Experimental: Expansion phase
    X1 mg IV every 2 weeks followed by X1 or X4 mg every 2 weeks
    Intervention: Drug: Avelumab
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 Terminated
Actual Enrollment  ICMJE
 (submitted: June 27, 2019)
33
Original Estimated Enrollment  ICMJE
 (submitted: November 10, 2015)
70
Actual Study Completion Date  ICMJE April 11, 2019
Actual Primary Completion Date December 1, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
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 Italy,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02603419
Other Study ID Numbers  ICMJE B9991007
2015-002636-41 ( EudraCT Number )
JAVELIN HODGKINS ( Other Identifier: Alias Study Number )
JAVELIN HODGKIN'S ( Other Identifier: Alias Study Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
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.
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date July 2019

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