Skip to main content
OpenTrials
Completed

NCT Number: NCT02331368

Phase 2 Multi-center Study of Anti-PD-1 During Lymphopenic State After 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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

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

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Autologous Stem Cell Transplant

Procedure

melphalan

Drug

140-200 mg/m^2

Lenalidomide

Drug

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

MK-3475

Drug

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

Other names: Anti-PD-1, Pembrolizumab

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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. The Estimated Percentage of Patients Alive at 2 Years

    Time frame: 2 Years

Sponsors and collaborators

Lead sponsor

University of Michigan Rogel Cancer Center

Other

Collaborators

  • Medical College of Wisconsin

Registry information

Official study 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

Important dates

Study start
2015
Primary completion
2017
Study completion
2017
First posted
Jan 6, 2015
Registry last updated
Jul 27, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.