Pembrolizumab + Lenalidomide Post Autologous Stem Cell Transplant (ASCT) in High-risk Multiple Myeloma (MM)

NCT02906332 | Terminated Phase 2 Results DMC

• 1 other identifier: Pro2016-0262
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  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.

  Up to 3 years

Secondary Outcomes (4)

• Number of Participants Serious Adverse Events

  Up to 3 years

• Evaluation of Stringent Complete Response, Complete Response, and Very Good Partial Response Rate (sCR + CR + VGPR Rate).

  Every 3 weeks (day 1 of every 21-day treatment cycle +/- 7 days) through 12 weeks.

• Number of Participants Who Progressed at 12 Months

  Time from Day 0 (transplant) and date of enrollment to study completion (through 12 weeks) by investigator assessment.

• Duration of Response (DOR)

  Interval between date of first response and date of study completion (through 12 weeks)

Other Outcomes (5)

• 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

  Bone marrow aspirate specimens will be obtained at screening and at week 15 (completion of cycle 4).

• Assessment of Immune Phenotype in Bone Marrow Aspirates and Peripheral Blood Samples and Plasma Cytokines.

  Obtained monthly through week 12 (cycle 4 day 1).

• Assessment of T Cell Repertoire in Bone Marrow Aspirates and Peripheral Blood Samples.

  Obtained monthly through week 12 (cycle 4 day 1).

Study Arms (1)

Pembrolizumab + lenalidomide

EXPERIMENTAL

This is an open label study. * Pembrolizumab 200 mg IV every 3 weeks and lenalidomide 25 mg po daily x 14 days and dexamethasone 40 mg po once weekly for a 21-day cycle x 2 cycles. * This is followed by pembrolizumab 200 mg every 3 weeks and lenalidomide 25 mg po daily x 14 days for a 21-day cycle x 2 cycles for a total of 4 cycles.

Drug: Pembrolizumab; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Pembrolizumab DRUG

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.

Also known as: Keytruda

Pembrolizumab + lenalidomide

Lenalidomide DRUG

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.

Also known as: Revlimid

Pembrolizumab + lenalidomide

Dexamethasone DRUG

Dexamethasone 40 mg po once weekly for a 21-day cycle x 2 cycles only.

Also known as: Decadron

Pembrolizumab + lenalidomide

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial.
• Be 18 years of age on day of signing informed consent.
• Has a confirmed diagnosis of MM based on standard criteria. (See Appendix 2 for MM Diagnostic Criteria.)
• Is between 60 and 180 days from peripheral blood autologous stem cell transplant.
• At diagnosis, had MM with measurable disease, defined as:
• A monoclonal immunoglobulin spike on serum electrophoresis of at least 0.5 g/dL and/or
• Urine monoclonal levels of at least 200 mg/24 hours
• For subjects without measurable serum and urine M-protein levels, an abnormal free light chain (FLC) ratio (normal value 0.26 - 1.65) with involved FLC ≥10 mg/dL
• Radiographic evidence of disease for those without measurable M-spike or free light chains.
• Has high-risk MM, which must be present at the time of diagnosis, and defined by:
• International Staging System (ISS) stage 3 (See Appendix 3 for ISS Staging), and/or
• Deletion 13q by cytogenetics, and/or
• q amplification, 1p deletion, p53 deletions (17p deletions), t(4;14), t(14;16), t(14;20), hypodiploidy, and/or
• High-risk gene expression profile (GEP) scores
• Be able to provide a newly obtained bone marrow aspirate/biopsy material for biomarker analysis and disease assessment.

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids may be used at the investigator's discretion.
• Has received an allogeneic stem cell transplant.
• Has received any myeloma-directed therapy after ASCT.
• Has a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Progressive disease from autologous transplantation at the time of screening
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has an active infection requiring intravenous systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

Sponsors & Collaborators

• Hackensack Meridian Health: lead

Study Sites (1)

John Theurer Cancer Center-Hackensack Meridian Health

Hackensack, New Jersey, 07601, United States

Location

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• Richardson PG, Schlossman RL, Weller E, Hideshima T, Mitsiades C, Davies F, LeBlanc R, Catley LP, Doss D, Kelly K, McKenney M, Mechlowicz J, Freeman A, Deocampo R, Rich R, Ryoo JJ, Chauhan D, Balinski K, Zeldis J, Anderson KC. Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma. Blood. 2002 Nov 1;100(9):3063-7. doi: 10.1182/blood-2002-03-0996.

  PMID: 12384400 BACKGROUND

• Chen C, R.D., Siegel D, et al., Expanded access program (EAP) for lenalidomide plus dexamethasoen in over 1400 subjects with relapsed or refractory multiple myeloma. Blood (ASH Annual Meeting Abstracts), 2006. 108(Abstract 3556).

  BACKGROUND

• Rajkumar SV, Jacobus S, Callander NS, Fonseca R, Vesole DH, Williams ME, Abonour R, Siegel DS, Katz M, Greipp PR; Eastern Cooperative Oncology Group. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol. 2010 Jan;11(1):29-37. doi: 10.1016/S1470-2045(09)70284-0. Epub 2009 Oct 21.

  PMID: 19853510 BACKGROUND

• Benboubker L, Dimopoulos MA, Dispenzieri A, Catalano J, Belch AR, Cavo M, Pinto A, Weisel K, Ludwig H, Bahlis N, Banos A, Tiab M, Delforge M, Cavenagh J, Geraldes C, Lee JJ, Chen C, Oriol A, de la Rubia J, Qiu L, White DJ, Binder D, Anderson K, Fermand JP, Moreau P, Attal M, Knight R, Chen G, Van Oostendorp J, Jacques C, Ervin-Haynes A, Avet-Loiseau H, Hulin C, Facon T; FIRST Trial Team. Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med. 2014 Sep 4;371(10):906-17. doi: 10.1056/NEJMoa1402551.

  PMID: 25184863 BACKGROUND

• Durie BG, Harousseau JL, Miguel JS, Blade J, Barlogie B, Anderson K, Gertz M, Dimopoulos M, Westin J, Sonneveld P, Ludwig H, Gahrton G, Beksac M, Crowley J, Belch A, Boccadaro M, Cavo M, Turesson I, Joshua D, Vesole D, Kyle R, Alexanian R, Tricot G, Attal M, Merlini G, Powles R, Richardson P, Shimizu K, Tosi P, Morgan G, Rajkumar SV; International Myeloma Working Group. International uniform response criteria for multiple myeloma. Leukemia. 2006 Sep;20(9):1467-73. doi: 10.1038/sj.leu.2404284. Epub 2006 Jul 20.

  PMID: 16855634 BACKGROUND

• Palumbo A, Dimopoulos M, San Miguel J, Harousseau JL, Attal M, Hussein M, Knop S, Ludwig H, von Lilienfeld-Toal M, Sonneveld P. Lenalidomide in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma. Blood Rev. 2009 Mar;23(2):87-93. doi: 10.1016/j.blre.2008.07.003. Epub 2008 Sep 6.

  PMID: 18774632 BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma

Interventions

pembrolizumab; Lenalidomide; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Joshua Zenreich
• Organization: Hackensack Meridian Health

joshua.zenreich@hmhn.org

15519964248

Study Officials

• Noa Biran, M.D.

  Hackensack Meridian Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2016
• First Posted: September 20, 2016
• Study Start: December 12, 2016
• Primary Completion: May 1, 2022
• Study Completion: May 1, 2022
• Last Updated: August 22, 2023
• Results First Posted: August 22, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)