Pembrolizumab After ASCT for Hodgkin Lymphoma, DLBCL and T-NHL

Sponsor
Dana-Farber Cancer Institute (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT02362997
Collaborator
Merck Sharp & Dohme Corp. (Industry)
83
Enrollment
6
Locations
3
Arms
98
Duration (Months)
13.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase II study is designed to determine the clinical efficacy of PD-1 blockade, using the anti-PD-1 monoclonal antibody pembrolizumab (MK-3475), administered as consolidation therapy after autologous stem cell transplant (ASCT), in patients with relapsed or refractory (R/R) Diffuse Large B Cell Lymphoma (DLBCL), classical Hodgkin Lymphoma (cHL) or peripheral T-cell lymphoma (PTCL) in 1st remission.

Detailed Description

Pembrolizumab is an antibody drug that blocks a molecule called PD-1. PD-1 is a receptor molecule on the surface of immune cells that can be used to turn off the immune response. Some cancers use this as a way to turn off the immune response against them. Blocking PD-1 with pembrolizumabmay restore an effective immune attack against the lymphoma cells.

On this study, patients who undergo ASCT for R/R cHL, DLBCL or PTCL in 1st remission will receive pembrolizumab at a dose of 200mg intravenously every 3 weeks for up to 8 cycles, beginning within a few weeks of ASCT.

Study Design

Study Type:
Interventional
Actual Enrollment :
83 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2 Study of Pembrolizumab (MK-3475) After Autologous Stem Cell Transplantation in Patients With Relapsed/Refractory Classical Hodgkin Lymphoma and, Diffuse Large B Cell Lymphoma and T- Cell Non-Hodgkin Lymphoma
Study Start Date :
Apr 1, 2015
Actual Primary Completion Date :
Oct 26, 2021
Anticipated Study Completion Date :
Jun 1, 2023

Arms and Interventions

ArmIntervention/Treatment
Experimental: Diffuse large B cell lymphoma

Pembrolizumab 200mg IV every 3 weeks up to 8 cycles

Drug: Pembrolizumab
Anti-PD-1 monoclonal antibody
Other Names:
  • Keytruda
  • MK-3475
  • SCH 900475
  • Experimental: Classical Hodgkin lymphoma

    Pembrolizumab 200mg IV every 3 weeks up to 8 cycles

    Drug: Pembrolizumab
    Anti-PD-1 monoclonal antibody
    Other Names:
  • Keytruda
  • MK-3475
  • SCH 900475
  • Experimental: Peripheral T cell lymphoma

    Pembrolizumab 200mg IV every 3 weeks up to 8 cycles

    Drug: Pembrolizumab
    Anti-PD-1 monoclonal antibody
    Other Names:
  • Keytruda
  • MK-3475
  • SCH 900475
  • Outcome Measures

    Primary Outcome Measures

    1. Progression-free survival after ASCT [18 Months]

      Proportion of patients alive and disease-free 18 months from ASCT

    Secondary Outcome Measures

    1. Overall Survival [18 Months]

      Proportion of patients alive 18 months from ASCT

    2. Relapse [18 Months]

      Incidence of relapse within 18 months from ASCT

    3. Safety and Tolerability assessed by Grade 2 and above toxicity related to study treatment [6 months]

    4. Response rate to pembrolizumab [18 months]

      In patients with measurable disease after ASCT, rate of objective response after treatment

    Other Outcome Measures

    1. Progression-free survival after ASCT by PET status [18 months]

      Proportion of patients alive and disease-free 18 months from ASCT stratified by PET status before transplantation

    2. Overall survival after ASCT by PET status [18 months]

      Proportion of patients alive 18 months from ASCT stratified by PET status before transplantation

    3. Completion rate [18 months]

      Proportion of patients who complete planned treatment

    4. Minimal residual disease [18 months]

      Level of MRD detected by PCR (if feasible) before and after pembrolizumab

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    • Histologically confirmed diagnosis with review of the diagnostic pathology specimen at one of the participating institutions. Eligible histologies are: Arm A: Diffuse large B cell lymphoma; patients with a prior history of indolent B-cell NHL are eligible, as long as they have histologically confirmed DLBCL prior to their pre-transplant salvage treatment. Patients with mediastinal large B cell lymphoma are also eligible.

    Arm B: Classical Hodgkin lymphoma (patients with nodular lymphocyte predominant Hodgkin lymphoma [NLPHL] are NOT eligible) Arm C: Peripheral T cell lymphoma - eligible subtypes will include PTCL, NOS; AITL; and ALK-negative ALCL. Patients with other PTCL histologies, including ALK-positive PTCL, and cutaneous T-cell lymphoma will not be eligible..

    • Age ≥ 18 at the time of enrollment.

    • For arms A and B, participants must have relapsed after or been refractory to first-line chemotherapy, i.e., they must have failed to achieve CR after first-line therapy or must have relapsed subsequently if they achieved CR. For arm C, participants will be eligible if transplant is performed as consolidation of first remission (partial or complete).

    • Participants must be planning to receive or have received autologous stem cell transplantation. Participants must have chemosensitive disease prior to ASCT, defined as achieving at least a partial remission (as determined with PET imaging) to salvage treatment. Participants with cHL or DLBCL (arms A and B) transplanted in 1st remission after only one line of treatment are not eligible. Participants with PTCL (arm C) transplanted beyond 1st remission are also not eligible.

    • No more than 1 line of anthracycline-containing chemotherapy prior to ASCT, and no more than 3 lines of therapy total prior to ASCT for arms A and B; no more than 1 line of therapy prior to ASCT for arm C.

    • Participants cannot have received any anti-neoplastic therapy (including radiotherapy, chemotherapy or immunotherapy) after ASCT

    • Participants must have had PET-CT for restaging after salvage therapy and before ASCT.

    • Participants must begin study treatment no later than 21 days from the post-ASCT discharge. Additionally, they must have recovered from ASCT toxicities at the time of first study treatment.

    • ECOG performance status ≤2

    • Participants must have normal organ and marrow function as defined below:

    • absolute neutrophil count ≥ 1,000/mcL

    • platelets ≥ 50,000/mcL

    • Hemoglobin ≥ 8 g/dl

    • total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN), or direct bilirubin ≤ ULN in patients with Gilbert's syndrome

    • AST(SGOT)/ALT(SGPT) ≤ 2.5 × ULN

    • Creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 60 mL/min/1.73 m2

    • Resting and ambulatory oxygen saturation ≥ 94% on room air

    • FEV1 and DLCO (adjusted for Hemoglobin) ≥ 50% predicted

    • Willigness to use contraception

    • Ability to understand and the willingness to sign a written informed consent document.

    Exclusion criteria

    • Participants who are receiving any other investigational agents after ASCT.

    • Participants with active CNS involvement are excluded.

    • History of or active autoimmune disease, or other syndrome that requires systemic steroids or autoimmune agents. Participants with vitiligo, resolved childhood asthma or atopy, hypothyroidism, or Sjogren's syndrome, as well as participants requiring only intranasal steroids, intermittent use of bronchodilators, local steroid injections, or physiologic replacement doses of prednisone (≤ 10 mg/d) are not excluded from this study.

    • History of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab. Prior hypersensitivity reactions to anti-CD20 therapy or anti-CD30 therapy is not an exclusion criterion.

    • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.

    • Receipt of > 600 mg/m2 total dose of BCNU with prior treatments including transplant conditioning regimen.

    • Uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or pose excess risk to the participant in the opinion of the treating clinician..

    • Pregnant or lactating women.

    • HIV-positive.

    • Participants with active viral hepatitis (positive HepB sAg, positive HepB core Ab with positive HepB viral load, or positive HepC antibody with positive HepC viral load).

    • Receipt of a live vaccine within 30 days of the start of treatment. Examples are measles, mumps, rubella, varicella, yellow fever, rabies, BCG, oral polio vaccine, and oral typhoid vaccine.

    • Prior treatment with an anti PD-1, anti PD-L1, or anti CTLA-4 agent. Participants who entered clinical remission with one of those agents and proceeded to ASCT without intervening relapse may be eligible after discussion with the Study Chair. Note that for patients who enter remission with checkpoint blockade therapy, this will not count towards the 3 lines of prior therapy.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1City of Hope National Medical CenterDuarteCaliforniaUnited States91010
    2Massachusetts General HospitalBostonMassachusettsUnited States02114
    3Beth Israel Deaconess Medical CenterBostonMassachusettsUnited States02215
    4Dana Farber Cancer InstituteBostonMassachusettsUnited States02215
    5Memorial Sloan Kettering Cancer CenterNew YorkNew YorkUnited States10065
    6MD Anderson Cancer CenterHoustonTexasUnited States77030

    Sponsors and Collaborators

    • Dana-Farber Cancer Institute
    • Merck Sharp & Dohme Corp.

    Investigators

    • Principal Investigator: Philippe Armand, MD, PhD, Dana-Farber Cancer Institute

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Philippe Armand, MD, PhD, Principal Investigator, Dana-Farber Cancer Institute
    ClinicalTrials.gov Identifier:
    NCT02362997
    Other Study ID Numbers:
    • 14-566
    First Posted:
    Feb 13, 2015
    Last Update Posted:
    Mar 31, 2022
    Last Verified:
    Mar 1, 2022

    Study Results

    No Results Posted as of Mar 31, 2022