NCT02362997
Completed
Phase 2
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
InterventionsPembrolizumab
DrugsPembrolizumab
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Hodgkin Lymphoma
- Sponsor
- Dana-Farber Cancer Institute
- Enrollment
- 82
- Locations
- 6
- Primary Endpoint
- Progression-free Survival After ASCT
- Status
- Completed
- Last Updated
- 2 months ago
Overview
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.
Investigators
Philippe Armand, MD, PhD
Principal Investigator
Dana-Farber Cancer Institute
Eligibility Criteria
Inclusion 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
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).
Arms & Interventions
Diffuse large B cell lymphoma
Pembrolizumab 200mg IV every 3 weeks up to 8 cycles
Intervention: Pembrolizumab
Peripheral T cell lymphoma
Pembrolizumab 200mg IV every 3 weeks up to 8 cycles
Intervention: Pembrolizumab
Classical Hodgkin lymphoma
Pembrolizumab 200mg IV every 3 weeks up to 8 cycles
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
Progression-free Survival After ASCT
Time Frame: 18 Months
Proportion of patients alive and disease-free 18 months from autologous stem cell transplantation (ASCT). Progression criteria are per Lugano 2014 criteria. All patients receiving any amount of protocol treatment. Patients who have progressed or lost to follow-up prior to 18 months are counted as failures; only patients followed and progression-free for at least 18 months are counted as successes.
Secondary Outcomes
- Relapse(18 Months)
- Safety and Tolerability Assessed by CTCAE v4 Grade 2 and Above Toxicity Related to Study Treatment(6 months)
- Progression-free Survival(18 months)
- Overall Survival(18 Months)
- Response Rate to Pembrolizumab(18 months)
Study Sites (6)
Loading locations...
Similar Trials
Completed
Phase 2
Pembrolizumab Alone or With Idelalisib or Ibrutinib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Other Low-Grade B-Cell Non-Hodgkin LymphomasRecurrent B-Cell Non-Hodgkin LymphomaRecurrent Chronic Lymphocytic LeukemiaRecurrent Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid TissueRecurrent Grade 1 Follicular LymphomaRecurrent Grade 2 Follicular LymphomaRecurrent Grade 3 Follicular LymphomaRecurrent Lymphoplasmacytic LymphomaRecurrent Marginal Zone LymphomaRecurrent Nodal Marginal Zone LymphomaRecurrent Small Lymphocytic LymphomaRecurrent Splenic Marginal Zone LymphomaRecurrent Waldenstrom MacroglobulinemiaRefractory B-Cell Non-Hodgkin LymphomaRefractory Chronic Lymphocytic LeukemiaRefractory Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid TissueRefractory Follicular LymphomaRefractory Lymphoplasmacytic LymphomaRefractory Nodal Marginal Zone LymphomaRefractory Small Lymphocytic LymphomaRefractory Splenic Marginal Zone LymphomaRefractory Waldenstrom MacroglobulinemiaRichter SyndromeWaldenstrom MacroglobulinemiaNCT02332980Mayo Clinic65
Active, Not Recruiting
Phase 2
Pembrolizumab in Treating Patients With Stage IV Metastatic or Recurrent Inflammatory Breast Cancer or Triple-Negative Breast Cancer Who Have Achieved Clinical Response or Stable Disease to Prior ChemotherapyEdemaErythemaEstrogen Receptor NegativeHER2/Neu NegativePeau d'OrangeProgesterone Receptor NegativeRecurrent Inflammatory Breast CarcinomaStage IV Inflammatory Breast CarcinomaTriple-Negative Breast CarcinomaNCT02411656M.D. Anderson Cancer Center71
Active, Not Recruiting
Phase 2
Pembrolizumab in Treating Patients With Desmoplastic Melanoma That Can or Cannot Be Removed by SurgeryDesmoplastic MelanomaNCT02775851National Cancer Institute (NCI)57
Completed
Phase 1
Pembrolizumab, Paclitaxel, Carboplatin, and Radiation Therapy in Treating Patients With Stage II-IIIB Non-Small Cell Lung CancerStage II Non-Small Cell Lung CancerStage IIIA Non-Small Cell Lung CancerStage IIIB Non-Small Cell Lung CancerNCT02621398Rutgers, The State University of New Jersey23
Active, Not Recruiting
Phase 2
Pembrolizumab and Carboplatin for the Treatment of Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal CancerRecurrent Fallopian Tube CarcinomaRecurrent Ovarian CarcinomaRecurrent Primary Peritoneal CarcinomaNCT04387227University of Washington22