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

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ClinicalTrials.gov Identifier: NCT02362997
Recruitment Status : Active, not recruiting
First Posted : February 13, 2015
Last Update Posted : September 30, 2020
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Philippe Armand, MD, PhD, Dana-Farber Cancer Institute

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.

Condition or disease Intervention/treatment Phase
Hodgkin Lymphoma Diffuse Large B Cell Lymphoma Peripheral T-Cell Lymphoma Drug: Pembrolizumab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
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 : April 2015
Estimated Primary Completion Date : February 2022
Estimated Study Completion Date : June 2023


Arm Intervention/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




Primary Outcome Measures :
  1. Progression-free survival after ASCT [ Time Frame: 18 Months ]
    Proportion of patients alive and disease-free 18 months from ASCT


Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: 18 Months ]
    Proportion of patients alive 18 months from ASCT

  2. Relapse [ Time Frame: 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 [ Time Frame: 6 months ]
  4. Response rate to pembrolizumab [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 18 months ]
    Proportion of patients alive 18 months from ASCT stratified by PET status before transplantation

  3. Completion rate [ Time Frame: 18 months ]
    Proportion of patients who complete planned treatment

  4. Minimal residual disease [ Time Frame: 18 months ]
    Level of MRD detected by PCR (if feasible) before and after pembrolizumab



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02362997


Locations
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United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Dana-Farber Cancer Institute
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: Philippe Armand, MD, PhD Dana-Farber Cancer Institute
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Philippe Armand, MD, PhD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT02362997    
Other Study ID Numbers: 14-566
First Posted: February 13, 2015    Key Record Dates
Last Update Posted: September 30, 2020
Last Verified: September 2020
Keywords provided by Philippe Armand, MD, PhD, Dana-Farber Cancer Institute:
Classical Hodgkin Lymphoma (cHL)
Diffuse Large B Cell Lymphoma (DLBCL)
Peripheral T-cell lymphoma (PTCL)
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, B-Cell
Hodgkin Disease
Lymphoma, T-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, T-Cell, Peripheral
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents