Clinical Trials /

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

NCT02362997

Description:

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.

Related Conditions:
  • Anaplastic Large Cell Lymphoma, ALK-Negative
  • Angioimmunoblastic T-Cell Lymphoma
  • Classical Hodgkin Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Mediastinal Large B-Cell Lymphoma
  • Peripheral T-Cell Lymphoma
  • Peripheral T-Cell Lymphoma, NOS
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab After ASCT for Hodgkin Lymphoma, DLBCL and T-NHL
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 14-566
  • NCT ID: NCT02362997

Conditions

  • Hodgkin Lymphoma
  • Diffuse Large B Cell Lymphoma
  • Peripheral T-Cell Lymphoma

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, MK-3475, SCH 900475Classical Hodgkin lymphoma

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Diffuse large B cell lymphomaExperimentalPembrolizumab 200mg IV every 3 weeks up to 8 cycles
  • Pembrolizumab
Classical Hodgkin lymphomaExperimentalPembrolizumab 200mg IV every 3 weeks up to 8 cycles
  • Pembrolizumab
Peripheral T cell lymphomaExperimentalPembrolizumab 200mg IV every 3 weeks up to 8 cycles
  • Pembrolizumab

Eligibility Criteria

        • 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival after ASCT
Time Frame:18 Months
Safety Issue:
Description:Proportion of patients alive and disease-free 18 months from ASCT

Secondary Outcome Measures

Measure:Overall Survival
Time Frame:18 Months
Safety Issue:
Description:Proportion of patients alive 18 months from ASCT
Measure:Relapse
Time Frame:18 Months
Safety Issue:
Description:Incidence of relapse within 18 months from ASCT
Measure:Safety and Tolerability assessed by Grade 2 and above toxicity related to study treatment
Time Frame:6 months
Safety Issue:
Description:
Measure:Response rate to pembrolizumab
Time Frame:18 months
Safety Issue:
Description:In patients with measurable disease after ASCT, rate of objective response after treatment

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Classical Hodgkin Lymphoma (cHL)
  • Diffuse Large B Cell Lymphoma (DLBCL)
  • Peripheral T-cell lymphoma (PTCL)

Last Updated

September 14, 2019