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

Primary Purpose

Multiple Myeloma

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Autologous Stem Cell Transplant

Melphalan

Lenalidomide

MK-3475

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple Myeloma, Anti-PD-1, Pembrolizumab, Post-transplant, Maintenance

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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
Has known symptomatic heart failure, unstable angina pectoris, or cardiac arrhythmia
Has received any type of hematopoietic cell transplant
Has received a live vaccine within 30 days of transplant admission
Is or has an immediate family member whos is investigational site or sponsor staff directly involved with this study

Sites / Locations

University of Michigan Comprehensive Cancer Center
Medical College of Wisconsin

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Anti-PD-1 (MK-3475)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Progression is defined as an increase of ≥ 25% from the lowest response value in any one or more of the following: Serum M-component with an absolute increase ≥ 0.5 g/dL; and/or Urine M-component with an absolute increase ≥ 200 mg/24 hours; and/or Only in patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels (absolute increase must be >100mg/l) Bone marrow plasma cell percentage (absolute % must be ≥10% Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas Development of hypercalcemia (corrected serum calcium >11.5mg/100ml) that can be attributed solely to the plasma cell proliferative disorder

The Estimated Percentage of Patients Alive at 2 Years

Full Information

NCT ID

NCT02331368

First Posted

January 2, 2015

Last Updated

July 2, 2018

Sponsor

University of Michigan Rogel Cancer Center

Collaborators

Medical College of Wisconsin

1. Study Identification

Unique Protocol Identification Number

NCT02331368

Brief Title

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

Official Title

Phase 2 Multi-center Study of Anti-Programmed-Death-1 [Anti-PD-1] During Lymphopenic State After High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplant [HDT/ASCT] for Multiple Myeloma

Study Type

Interventional

2. Study Status

Record Verification Date

July 2018

Overall Recruitment Status

Completed

Study Start Date

June 2015 (undefined)

Primary Completion Date

June 2017 (Actual)

Study Completion Date

June 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Michigan Rogel Cancer Center

Collaborators

Medical College of Wisconsin

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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. 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. Studies further showed enhancement of this "unleash" after autologous transplant and better MM control by anti-PD1 when used after transplant. 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. Thus, investigators proposed an efficacy study of anti-PD1 treatment after transplant to improve MM treatment outcomes. This was a collaborative study with Medical College of Wisconsin (headquarter of Center for International blood and Marrow Transplant Research). Investigators hypothesized that anti-PD1 treatment would increase the MM response and the MM control duration when added to the standard MM treatment after transplant. Anti-PD1 was given at the dose and interval, which had been studied previously (200 mg intravenous injection every 3 weeks) between 2 weeks until 6 months after transplant. Subjects were monitored closely during and after anti-PD1 therapy until at least 1 year post transplant. Late complications were followed for 3 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Myeloma

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

32 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Anti-PD-1 (MK-3475)

Arm Type

Experimental

Arm Description

Intervention Type

Procedure

Intervention Name(s)

Autologous Stem Cell Transplant

Intervention Type

Drug

Intervention Name(s)

Melphalan

Intervention Description

140-200 mg/m^2

Intervention Type

Drug

Intervention Name(s)

Lenalidomide

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

MK-3475

Other Intervention Name(s)

Anti-PD-1, Pembrolizumab

Intervention Description

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

Primary Outcome Measure Information:

Title

The Number of Patients That Achieve Complete Response

Description

Time Frame

180 days post-transplant

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

2 Years

Title

The Estimated Percentage of Patients Alive at 2 Years

Time Frame

2 Years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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 Has known symptomatic heart failure, unstable angina pectoris, or cardiac arrhythmia Has received any type of hematopoietic cell transplant Has received a live vaccine within 30 days of transplant admission Is or has an immediate family member whos is investigational site or sponsor staff directly involved with this study

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Attaphol Pawarode, M.D.

Organizational Affiliation

University of Michigan Rogel Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Michigan Comprehensive Cancer Center

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109

Country

United States

Facility Name

Medical College of Wisconsin

City

Milwaukee

State/Province

Wisconsin

ZIP/Postal Code

53226

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

30959163

Citation

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.

Results Reference

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

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