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

July 2, 2018 updated by: University of Michigan Rogel Cancer Center

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

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. 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. Studies further showed enhancement of this "unleash" after autologous transplant and better MM control by anti-PD1 when used after transplant.
  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.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

32

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Comprehensive Cancer Center
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Anti-PD-1 (MK-3475)

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
140-200 mg/m^2
Drug: Lenalidomide
5-15 mg/day starting 45-90 days post-transplant
Drug: MK-3475
200 mg/day every 3 weeks starting day +14 post-transplant for a total of 9 doses.
Other Names:
  • Pembrolizumab
  • Anti-PD-1

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Number of Patients That Achieve Complete Response
Time Frame: 180 days post-transplant
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Estimated Percentage of Patients Alive Without Relapse or Progression at 2 Years
Time Frame: 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
2 Years
The Estimated Percentage of Patients Alive at 2 Years
Time Frame: 2 Years
2 Years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Michigan Rogel Cancer Center

Collaborators

Medical College of Wisconsin

Investigators

  • Principal Investigator: Attaphol Pawarode, M.D., University of Michigan Rogel Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2015

Primary Completion (Actual)

June 1, 2017

Study Completion (Actual)

June 1, 2017

Study Registration Dates

First Submitted

January 2, 2015

First Submitted That Met QC Criteria

January 2, 2015

First Posted (Estimate)

January 6, 2015

Study Record Updates

Last Update Posted (Actual)

July 27, 2018

Last Update Submitted That Met QC Criteria

July 2, 2018

Last Verified

July 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UMCC 2014.134

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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