Nivolumab for Relapsed, Refractory, or Detectable Disease Post Chimeric Antigen Receptor T-cell Treatment in Patients With Hematologic Malignancies

April 9, 2024 updated by: University of Washington

Nivolumab for Relapsed or Refractory Disease Post Chimeric Antigen Receptor T-Cell Treatment in Patients With Hematologic Malignancies

This phase II trial studies how well nivolumab works for the treatment of hematological malignancies that have come back (relapsed), does not respond (refractory), or is detectable after CAR T cell therapy. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

OUTLINE:

Patients receive nivolumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days and then for up to 5 years.

Study Type

Interventional

Enrollment (Actual)

20

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 Contact

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutch/University of Washington Cancer Consortium

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosis of the following tumor types

    • Non Hodgkin-lymphoma, including:

      • Diffuse large B-cell lymphoma: Histopathologic confirmation
      • Mantle cell lymphoma: Histopathologic confirmation
      • Follicular lymphoma, all grades: Histopathologic confirmation
      • Marginal zone lymphoma: Histopathologic confirmation
    • Chronic lymphocytic leukemia: Histopathologic or flow cytometric confirmation
    • Multiple myeloma: Histopathologic or flow confirmation

  • Relapsed, refractory, or detectable disease after treatment with chimeric antigen receptor T-cells

    * Multiple Myeloma: patients must have exhausted all treatment options known to provide clinical benefit, and are refractory to a minimum of 3 prior lines of therapy (including an immunomodulatory imide drug [IMiD], proteasome inhibitor [PI], or anti-CD38 monoclonal antibody)

  • Have measurable disease, defined by histology:

    • Non-Hodgkin's lymphoma, based on presence of lesions >= 1.5 cm that can be accurately measured in 2 dimensions by computed tomography (CT) (preferred) or magnetic resonance imaging (MRI), and are not included in any prior field of radiation therapy
    • Chronic lymphocytic leukemia: circulating lymphocytes >= 5,000 / mm^3

    • Multiple myeloma, based on the International Myeloma Working Group (IMWG) criteria of having one or more of the following findings:

      • Serum M protein >= 1.0 g/dL
      • Urine M protein >= 200 mg/24 hours
      • Involved serum free light chain level >= 10 mg/dL with abnormal kappa/lambda ratio
      • Measurable biopsy-proven plasmacytomas (>= 1 lesion has a single diameter >= 2 cm)
      • Bone marrow plasma cells >= 30%
  • Age 18 years and older, and have the capacity to give informed consent
  • Anticipated survival of > 3 months
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Post CAR T cell receipt of intervening palliative radiation therapy is allowed
  • Estimated glomerular filtration rate (eGFR) >= 20 ml/min
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x upper limit of normal (ULN)
  • Total bilirubin =< 2 x ULN
  • Absolute neutrophil count (ANC) >= 1,000/uL
  • Platelets >= 50,000/uL
  • Hemoglobin >= 8 g/dL

Exclusion Criteria:

  • Receipt of intervening therapy after CAR T-cell infusion
  • History of another primary malignancy that has not been in remission for at least 1 year (with the exception of non-melanoma skin cancer, curatively treated localized prostate cancer, curatively treated superficial bladder cancer and cervical carcinoma in site on biopsy or a squamous intraepithelial lesion on papanicolaou [PAP] smear)
  • Active hepatitis B, hepatitis C at time of screening
  • Known (human immunodeficiency virus [HIV]) seropositivity
  • Subjects with uncontrolled infection
  • Concurrent use of other anticancer agents or experimental treatments
  • Active autoimmune disease requiring immunosuppressive therapy with the exception of vitiligo and autoimmune alopecia
  • Known active central nervous system (CNS) involvement
  • Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses are permitted in absence of active autoimmune disease
  • Known history of any active infectious pneumonitis
  • Presence of acute or chronic graft-versus-host disease (GVHD) requiring active treatment unless limited to skin involvement and managed with topical steroid therapy alone
  • Has active cytokine release syndrome
  • Pregnancy or breastfeeding: Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (urine pregnancy test: minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [hCG]) within 14 days of the first dose of study drug. Women must not be breastfeeding. Females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy. Females of childbearing potential and males who have partners of childbearing potential must agree to use 2 effective contraceptive methods during the study and for 8 months following the last dose of nivolumab

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: Treatment (nivolumab)
Patients receive nivolumab IV over 30 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
  • CMAB819
  • Nivolumab Biosimilar CMAB819
  • 946414-94-4

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Best overall response rate (ORR)
Time Frame: Up to 5 years
Assessed by disease-specific guidelines: multiple myeloma - International Myeloma Working Group response criteria, non-Hodgkin lymphoma - Response assessment will be based on the Lugano Criteria, and chronic lymphocytic leukemia - Response assessment based on the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria. ORR will be estimated, and its corresponding 95% exact binomial confidence interval (CI) will be provided.
Up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: From the first study drug administration to death from any cause, up to 5 years
Will employ Kaplan-Meier and Cox proportional hazard model methodology.
From the first study drug administration to death from any cause, up to 5 years
Progression-free survival
Time Frame: From first study drug administration to the first occurrence of disease progression or death from any cause, assessed up to 5 years
Will employ Kaplan-Meier and Cox proportional hazard model methodology.
From first study drug administration to the first occurrence of disease progression or death from any cause, assessed up to 5 years
Duration of response
Time Frame: Up to 5 years
Will employ Kaplan-Meier and Cox proportional hazard model methodology.
Up to 5 years
Incidence of adverse events
Time Frame: Up to 30 days after the last dose of study drug
Will be determined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Safety data will be summarized descriptively. Adverse events will be summarized by severity, seriousness, and relationship to study drug.
Up to 30 days after the last dose of study drug

Collaborators and Investigators

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

Sponsor

University of Washington

Collaborators

Bristol-Myers Squibb

Investigators

  • Principal Investigator: Andrew Cowan, Fred Hutch/University of Washington Cancer Consortium

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 (Actual)

June 5, 2020

Primary Completion (Estimated)

April 5, 2025

Study Completion (Estimated)

August 1, 2029

Study Registration Dates

First Submitted

December 17, 2019

First Submitted That Met QC Criteria

December 17, 2019

First Posted (Actual)

December 19, 2019

Study Record Updates

Last Update Posted (Actual)

April 11, 2024

Last Update Submitted That Met QC Criteria

April 9, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RG1005491
  • NCI-2019-08192 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • 10388 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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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