Phase 2 Multi-center Study of Anti-PD-1 During Lymphopenic State After HDT/ASCT for Multiple Myeloma

NCT02331368 | Completed Phase 2 Results DMC

• 1 other identifier: UMCC 2014.134
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

Multiple myeloma (MM) is a common incurable blood cancer causing debilitating symptoms-bone pain, kidney failure, low blood counts and infection. Chemotherapy outcomes are disappointing due to short-term response and long-term toxicities.

1. 1.Studies showed these patients have weak immune against MM due to the immune checkpoint mediated by the PD1/PD-L1 interaction between immune cells and MM. Anti-PD-1 antibody (anti-PD1) disrupts this interaction, thus unleashing immune cell function and leading to killing of MM cells.
2. 2.Studies further showed enhancement of this "unleash" after autologous transplant and better MM control by anti-PD1 when used after transplant.
3. 3.Anti-PD1 has been extensively studied in patients with other cancers. It is very safe and effective and has been FDA-approved. Complications are of mild degree and easy to manage successfully in out-patient setting. Severe complications are rare.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Anti-PD-1; Pembrolizumab; Post-transplant; Maintenance

Outcome Measures

Primary Outcomes (1)

• The Number of Patients That Achieve Complete Response

  The primary efficacy endpoint is complete response rate. The complete response rate was estimated by the observed proportion of complete responders at day 180. Complete response (CR) was defined as negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas, and \<5% plasma cells in bone marrow and negative bone marrow flow cytometry.

  180 days post-transplant

Secondary Outcomes (2)

• The Estimated Percentage of Patients Alive Without Relapse or Progression at 2 Years

  2 Years

• The Estimated Percentage of Patients Alive at 2 Years

  2 Years

Study Arms (1)

Anti-PD-1 (MK-3475)

EXPERIMENTAL

Standard Treatment: High-dose Melphalan and autologous stem cell transplantation with post-transplant maintenance of Lenalidomide. Study Treatment: 200 mg/day of MK-3475 administered every 3 weeks, starting day +14 post-transplant for a total of 9 doses.

Procedure: Autologous Stem Cell Transplant; Drug: Melphalan; Drug: Lenalidomide; Drug: MK-3475

Interventions

Autologous Stem Cell Transplant PROCEDURE

Anti-PD-1 (MK-3475)

Melphalan DRUG

140-200 mg/m\^2

Anti-PD-1 (MK-3475)

Lenalidomide DRUG

5-15 mg/day starting 45-90 days post-transplant

Anti-PD-1 (MK-3475)

MK-3475 DRUG

200 mg/day every 3 weeks starting day +14 post-transplant for a total of 9 doses.

Also known as: Anti-PD-1, Pembrolizumab

Anti-PD-1 (MK-3475)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with MM (Multiple Myeloma) of any stage
• Has no Progressive Disease (PD) AND has suboptimal response with primary therapy
• Has measurable disease
• Has no prior hematopoietic stem cell transplant of any type
• Has performance status of 0 or 1 (Eastern Cooperative Oncology, ECOG, Performance Scale)
• Has had a successful peripheral blood stem cell collection with G-CSF (Filgrastim) +/- Plerixafor (Mozobil) only
• Be willing and able to provide written informed consent
• Female subjects of child bearing age should have negative urine or serum pregnancy test
• Female subjects of child bearing age must be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity
• Male subjects must agree to use an adequate method of contraception
• Subject must be able to swallow capsules
• Must demonstrate adequate organ function

You may not qualify if:

• Has history of repeat infections, amyloidosis, hyperviscosity, plasma cell leukemia, POEMS syndrome, Waldenstrom's macroglobulinemia, non-secretory multiple myeloma, or IgM myeloma
• Has known CNS (Central Nervous System) involvement or history of resolved CNS involvement
• Has an active autoimmune disease or history of autoimmune disease that requires systemic treatment with steroids of immunosuppressive agents.
• Has active, non-infectious pneumonitis
• Has diagnosis of immunosuppressive disorder or on immunosuppressive therapy within 7 days of transplant admission
• Is currently participating in or has previously participated in the study of an investigational drug/device within 4 weeks of transplant admission
• Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or CTLA-4
• Has had prior monoclonal antibody, chemotherapy, small molecule therapy, or radiation within 2 weeks of transplant admission
• Has not recovered from adverse events due to previously administered agent
• Must be free of additional malignancy for at least 5 years
• Has an active infection requiring systemic therapy
• Has known psychiatric or substance abuse disorders that would interfere with requirements of the study
• Is pregnant or breastfeeding or expecting to conceive
• Has known HIV, Hepatitis B, or Hepatitis C infection
• Has clinically significant coagulopathy

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• Medical College of Wisconsin: collaborator

Study Sites (2)

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• D'Souza A, Hari P, Pasquini M, Braun T, Johnson B, Lundy S, Couriel D, Hamadani M, Magenau J, Dhakal B, Shah NN, Riwes M, Parkin B, Reddy P, Pawarode A. A Phase 2 Study of Pembrolizumab during Lymphodepletion after Autologous Hematopoietic Cell Transplantation for Multiple Myeloma. Biol Blood Marrow Transplant. 2019 Aug;25(8):1492-1497. doi: 10.1016/j.bbmt.2019.04.005. Epub 2019 Apr 6.

  PMID: 30959163 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Melphalan; Lenalidomide; pembrolizumab; spartalizumab

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)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

The study was terminated during a pending major amendment after interim analysis and until the FDA mandate of the discontinuation of any combination therapy of MK-3475 and lenalidomide.

Results Point of Contact

• Title: Dr. Attaphol Pawarode, M.D.
• Organization: University of Michigan Comprehensive Cancer Center

pawarode@umich.edu

734-936-8785

Study Officials

• Attaphol Pawarode, M.D.

  University of Michigan Rogel Cancer Center

  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: January 2, 2015
• First Posted: January 6, 2015
• Study Start: June 1, 2015
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: July 27, 2018
• Results First Posted: July 27, 2018

Record last verified: 2018-07

Locations

US (2)