Pembrolizumab + Lenalidomide Post Autologous Stem Cell Transplant (ASCT) in High-risk Multiple Myeloma (MM)
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|ClinicalTrials.gov Identifier: NCT02906332|
Recruitment Status : Active, not recruiting
First Posted : September 20, 2016
Last Update Posted : February 20, 2019
This is an open-label, Phase II, single center trial of pembrolizumab (MK-3475), lenalidomide and dexamethasone in subjects with high risk Multiple Myeloma (hrMM) post high-dose chemotherapy with autologous stem cell transplantation (ASCT).
Patients with high-risk MM defined as those with one of the following abnormalities who have undergone induction therapy followed by single or tandem melphalan -based ASCT will be considered eligible.
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma||Drug: Pembrolizumab Drug: Lenalidomide Drug: Dexamethasone||Phase 2|
The primary objectives of this trial are to establish the progression free survival (PFS) of ASCT followed by consolidative therapy with pembrolizumab plus lenalidomide and dexamethasone and to evaluate the safety of pembrolizumab plus lenalidomide and dexamethasone following ASCT. The immunological analysis of cells and cytokines pre and post-therapy will be determined from patient bone marrow aspirate and peripheral blood samples as exploratory objectives. The overall composition of the gut microbiome will also be determined in patient stool samples.
Patients will be followed by response, EFS/PFS/OS and safety endpoints on an every 3 week basis. Bone marrow aspirate specimens will be obtained at screening and at completing of the study and peripheral blood specimens will be obtained on a monthly basis to evaluate in correlative studies.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||16 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Trial of the Anti -PD-1 Monoclonal Antibody Pembrolizumab (MK-3475) + Lenalidomide + Dexamethasone as Post Autologous Transplant Consolidation in Patients With High-risk Multiple Myeloma|
|Actual Study Start Date :||December 12, 2016|
|Estimated Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||July 2020|
Experimental: Pembrolizumab + lenalidomide
This is an open label study.
Pembrolizumab 200 mg IV every 3 weeks x 2 cycles. This is followed by followed by pembrolizumab 200 mg IV every 3 weeks for 2 additional cycles.
Other Name: Keytruda
Lenalidomide 25 mg po daily x 14 days once weekly for a 21-day cycle x 2 cycles. This is followed by lenalidomide 25 mg po daily x 14 days for a 21-day cycle x 2 cycles for 2 additional cycles.
Other Name: Revlimid
Dexamethasone 40 mg po once weekly for a 21-day cycle x 2 cycles only.
Other Name: Decadron
- Progression free survival (PFS) [ Time Frame: 12 Months ]PFS will be assessed from the date of ASCT, with day 0 defined as date of stem cell infusion (if tandem transplant the 2nd of 2 transplants will be used) until the date of progression, defined as the date at which the patient starts the next line of therapy or the date of death.
- Safety and tolerability of pembrolizumab (MK-3475), lenalidomide and dexamethasone following ASCT. [ Time Frame: Adverse events (AEs) assessed every 2 wks on treatment up to 30 days after last dose of study drug. Serious adverse events (SAEs) and events of clinical interest (ECIs) up to 90 days after last dose or start of new anti-cancer therapy, whichever is 1st. ]Safety will be assessed by quantifying the toxicities and grades experienced by subjects who have received pembrolizumab (MK-3475), lenalidomide and dexamethasone, including serious adverse events (SAEs).
- Evaluation of stringent complete response, complete response, and very good partial response rate (sCR + CR + VGPR rate) [ Time Frame: Every 3 weeks (day 1 of every 21-day treatment cycle +/- 7 days) through 12 weeks. ]Assessed by the investigator per International Myeloma Working Group criteria(IMWG) uniform response criteria.
- Time to Progression (TTP) [ Time Frame: Time from Day 0 (transplant) and date of enrollment to study completion (through 12 weeks) by investigator assessment. ]Assessed at 12 months; Subjects without documented PD or death will be censored at the last disease assessment date. Those who died without documented PD will be censored at the time of death.
- Duration of Response (DOR) [ Time Frame: Interval between date of first response and date of study completion (through 12 weeks) ]Assessed by the investigator per International Myeloma Working Group criteria(IMWG) uniform response criteria.
- Comparison in bone marrow aspirates of the extent of pre-pembrolizumab (MK-3475), lenalidomide and dexamethasone PD-L1 expression and change from baseline PD-L1 expression in responders versus non-responders [ Time Frame: Bone marrow aspirate specimens will be obtained at screening and at week 15 (completion of cycle 4). ]Comparison of change from baseline in bone marrow aspirate/biopsy PD-L1 expression between responders with longer duration of response and non-responders or responders with a short duration of response will be performed using mixed regression analysis. Longitudinal analysis of bone marrow aspirate/biopsy PD-L1 expression over time will be examined using mixed model repeated measure design with levels observed serially over time and response type (long responders vs short responders/non-response) as a fixed variable.
- Assessment of immune phenotype in bone marrow aspirates and peripheral blood samples and plasma cytokines. [ Time Frame: Obtained monthly through week 12 (cycle 4 day 1). ]Assays for these studies include flow cytometry, TCR Immunoseq for Vbeta CDR3 highest frequency specificities, real-time PCR analysis and multiplex cytokine ELISA. These data will be aggregated before and after treatment in responders versus non-responders.
- Assessment of T cell repertoire in bone marrow aspirates and peripheral blood samples. [ Time Frame: Obtained monthly through week 12 (cycle 4 day 1). ]Assays for these studies include flow cytometry, TCR Immunoseq for Vbeta CDR3 highest frequency specificities, and real-time PCR analysis. T cells (CD8+) data will be aggregated before and after treatment in responders versus non-responders.
- Assessment of plasma cytokines [ Time Frame: Obtained monthly through week 12 (cycle 4 day 1). ]Multiplex cytokine ELISA studies will assess inflammatory cytokine (TNF-alpha, IL-2, IL-4, IL-6, IL-10) data and will be aggregated before and after treatment in responders versus non-responders.
- Identification and assessment of specific intestinal microbial strains (via stool specimens) associated with improved outcome in autologous stem cell transplantation patients treated with PEM+LEN+DEX compared to PEM+LEN. [ Time Frame: Stool specimens at screening or cycle 1, day 1, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1, at completion of cycle 4, and at 90 days post treatment or start of new anti cancer therapy. Stool samples will also be collected at confirmation of response. ]A 16S ribosomal RNA (rRNA) miSeq Illumina platform will be used for overall microbial composition and quantitative real-time PCR analysis will validate the specific microbial strains identified by miSeq.
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): NCT02906332
|United States, New Jersey|
|John Theurer Cancer Center-Hackensack Meridian Health|
|Hackensack, New Jersey, United States, 07601|
|Principal Investigator:||Noa Biran, M.D.||Hackensack Meridian Health|