Diffuse Large B Cell Lymphoma, Hodgkin Lymphoma, Peripheral T-Cell Lymphoma
Conditions
Keywords
Classical Hodgkin Lymphoma (cHL), Diffuse Large B Cell Lymphoma (DLBCL), Peripheral T-cell lymphoma (PTCL)
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.
Interventions
DRUGPembrolizumab
Anti-PD-1 monoclonal antibody
Sponsors
Dana-Farber Cancer Institute
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival After ASCT | 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
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 18 Months | Survival probability of patients alive 18 months from ASCT, time-to-event |
| Relapse | 18 Months | Number of patients who relapse within 18 months from autologous stem cell transplantation. |
| Safety and Tolerability Assessed by CTCAE v4 Grade 2 and Above Toxicity Related to Study Treatment | 6 months | Number of patients who experienced at least a grade 2 toxicity with "definite," "probable," or "possible" attribute to study treatment, according to the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 |
| Response Rate to Pembrolizumab | 18 months | In patients with measurable disease after ASCT, rate of objective response after treatment. Response was assessed using the Lugano 2014 criteria. |
| Progression-free Survival | 18 months | Progression-free survival probability of patients who are alive and without progression 18 months from ASCT, time-to-event |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORReid Merryman, MD
Dana-Farber Cancer Institute
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Diffuse Large B Cell Lymphoma Pembrolizumab 200mg IV every 3 weeks up to 8 cycles
Pembrolizumab: Anti-PD-1 monoclonal antibody | 31 |
| Classical Hodgkin Lymphoma Pembrolizumab 200mg IV every 3 weeks up to 8 cycles
Pembrolizumab: Anti-PD-1 monoclonal antibody | 30 |
| Peripheral T Cell Lymphoma Pembrolizumab 200mg IV every 3 weeks up to 8 cycles
Pembrolizumab: Anti-PD-1 monoclonal antibody | 21 |
| Total | 82 |
Baseline characteristics
| Characteristic | Diffuse Large B Cell Lymphoma | Classical Hodgkin Lymphoma | Peripheral T Cell Lymphoma | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 1 Participants | 6 Participants | 15 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 29 Participants | 15 Participants | 67 Participants |
| Age, Continuous | 57 years | 34 years | 58 years | 50 years |
| ECOG Performance Score 00- Fully Active | 10 Participants | 14 Participants | 4 Participants | 28 Participants |
| ECOG Performance Score 01- Restricted | 20 Participants | 16 Participants | 16 Participants | 52 Participants |
| ECOG Performance Score 02- Ambulatory and Capable of Self Care | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 18 Participants | 13 Participants | 55 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants | 12 Participants | 8 Participants | 26 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 12 Participants | 8 Participants | 24 Participants |
| Race (NIH/OMB) White | 25 Participants | 17 Participants | 10 Participants | 52 Participants |
| Region of Enrollment United States | 31 participants | 30 participants | 21 participants | 82 participants |
| Sex: Female, Male Female | 9 Participants | 14 Participants | 9 Participants | 32 Participants |
| Sex: Female, Male Male | 22 Participants | 16 Participants | 12 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 31 | 0 / 30 | 3 / 21 |
| other Total, other adverse events | 29 / 31 | 30 / 30 | 21 / 21 |
| serious Total, serious adverse events | 8 / 31 | 3 / 30 | 1 / 21 |
Outcome results
Primary
Progression-free Survival After ASCT
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.
Time frame: 18 Months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Diffuse Large B Cell Lymphoma | Progression-free Survival After ASCT | 0.58 proportion of participants |
| Classical Hodgkin Lymphoma | Progression-free Survival After ASCT | 0.77 proportion of participants |
| Peripheral T Cell Lymphoma | Progression-free Survival After ASCT | 0.62 proportion of participants |
Secondary
Overall Survival
Survival probability of patients alive 18 months from ASCT, time-to-event
Time frame: 18 Months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Diffuse Large B Cell Lymphoma | Overall Survival | 0.93 survival probability |
| Classical Hodgkin Lymphoma | Overall Survival | 1.0 survival probability |
| Peripheral T Cell Lymphoma | Overall Survival | 0.94 survival probability |
Secondary
Progression-free Survival
Progression-free survival probability of patients who are alive and without progression 18 months from ASCT, time-to-event
Time frame: 18 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Diffuse Large B Cell Lymphoma | Progression-free Survival | 0.74 progression-free survival probability |
| Classical Hodgkin Lymphoma | Progression-free Survival | 0.87 progression-free survival probability |
| Peripheral T Cell Lymphoma | Progression-free Survival | 0.84 progression-free survival probability |
Secondary
Relapse
Number of patients who relapse within 18 months from autologous stem cell transplantation.
Time frame: 18 Months
Population: Patients who have been followed for at least 18 months or have relapsed prior to 18 months post ASCT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Diffuse Large B Cell Lymphoma | Relapse | 11 Participants |
| Classical Hodgkin Lymphoma | Relapse | 4 Participants |
| Peripheral T Cell Lymphoma | Relapse | 4 Participants |
Secondary
Response Rate to Pembrolizumab
In patients with measurable disease after ASCT, rate of objective response after treatment. Response was assessed using the Lugano 2014 criteria.
Time frame: 18 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Diffuse Large B Cell Lymphoma | Response Rate to Pembrolizumab | 0.74 proportion of participants |
| Classical Hodgkin Lymphoma | Response Rate to Pembrolizumab | 0.90 proportion of participants |
| Peripheral T Cell Lymphoma | Response Rate to Pembrolizumab | 0.86 proportion of participants |
Secondary
Safety and Tolerability Assessed by CTCAE v4 Grade 2 and Above Toxicity Related to Study Treatment
Number of patients who experienced at least a grade 2 toxicity with definite, probable, or possible attribute to study treatment, according to the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Diffuse Large B Cell Lymphoma | Safety and Tolerability Assessed by CTCAE v4 Grade 2 and Above Toxicity Related to Study Treatment | 21 Participants |
| Classical Hodgkin Lymphoma | Safety and Tolerability Assessed by CTCAE v4 Grade 2 and Above Toxicity Related to Study Treatment | 15 Participants |
| Peripheral T Cell Lymphoma | Safety and Tolerability Assessed by CTCAE v4 Grade 2 and Above Toxicity Related to Study Treatment | 12 Participants |
Other Pre-specified
Completion Rate
Number of patients who complete the planned treatment
Time frame: 18 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Diffuse Large B Cell Lymphoma | Completion Rate | 18 Participants |
| Classical Hodgkin Lymphoma | Completion Rate | 23 Participants |
| Peripheral T Cell Lymphoma | Completion Rate | 14 Participants |
Other Pre-specified
Minimal Residual Disease
Level of MRD detected by PCR (if feasible) before and after pembrolizumab
Time frame: 18 months
Other Pre-specified
Overall Survival After ASCT by PET Status
Survival probability of patients alive 18 months from ASCT stratified by PET status before transplantation, time-to-event. Patients categorized by complete metabolic response (complete response by PET scan, assessed using the Lugano 2014 criteria), partial response (assessed using Lugano 2014 criteria) prior to transplantation.
Time frame: 18 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Diffuse Large B Cell Lymphoma | Overall Survival After ASCT by PET Status | 0.94 survival probability |
| Classical Hodgkin Lymphoma | Overall Survival After ASCT by PET Status | 0.91 survival probability |
| Peripheral T Cell Lymphoma | Overall Survival After ASCT by PET Status | 1.0 survival probability |
| Classical Hodgkin Lymphoma - PET-NCR | Overall Survival After ASCT by PET Status | 1.0 survival probability |
| Peripheral T Cell - PET-CR | Overall Survival After ASCT by PET Status | 0.94 survival probability |
| Peripheral T Cell - PET-NCR | Overall Survival After ASCT by PET Status | 1.0 survival probability |
Other Pre-specified
Progression-free Survival After ASCT by PET Status
Progression-free survival probability of patients alive and disease-free 18 months from ASCT stratified by PET status before transplantation, time-to-event
Time frame: 18 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Diffuse Large B Cell Lymphoma | Progression-free Survival After ASCT by PET Status | 0.87 progression-free survival probability |
| Classical Hodgkin Lymphoma | Progression-free Survival After ASCT by PET Status | 0.54 progression-free survival probability |
| Peripheral T Cell Lymphoma | Progression-free Survival After ASCT by PET Status | 0.82 progression-free survival probability |
| Classical Hodgkin Lymphoma - PET-NCR | Progression-free Survival After ASCT by PET Status | 1.0 progression-free survival probability |
| Peripheral T Cell - PET-CR | Progression-free Survival After ASCT by PET Status | 0.82 progression-free survival probability |
| Peripheral T Cell - PET-NCR | Progression-free Survival After ASCT by PET Status | 1.0 progression-free survival probability |