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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04205409
Recruitment Status : Not yet recruiting
First Posted : December 19, 2019
Last Update Posted : May 29, 2020
National Cancer Institute (NCI)
Bristol-Myers Squibb
Information provided by (Responsible Party):
University of Washington

Brief Summary:
This phase II trial studies how well nivolumab works for the treatment of hematological malignancies that have come back (relapsed) or does not respond (refractory) 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.

Condition or disease Intervention/treatment Phase
Recurrent Chronic Lymphocytic Leukemia Recurrent Diffuse Large B-Cell Lymphoma Recurrent Follicular Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Grade 3a Follicular Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Non-Hodgkin Lymphoma Recurrent Plasma Cell Myeloma Refractory Chronic Lymphocytic Leukemia Refractory Diffuse Large B-Cell Lymphoma Refractory Follicular Lymphoma Refractory Marginal Zone Lymphoma Refractory Non-Hodgkin Lymphoma Refractory Plasma Cell Myeloma Biological: Nivolumab Phase 2

Detailed Description:


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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Nivolumab for Relapsed or Refractory Disease Post Chimeric Antigen Receptor T-Cell Treatment in Patients With Hematologic Malignancies
Estimated Study Start Date : June 4, 2020
Estimated Primary Completion Date : August 1, 2022
Estimated Study Completion Date : August 1, 2022

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:
  • 946414-94-4
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. Duration of response [ Time Frame: Up to 5 years ]
    Will employ Kaplan-Meier and Cox proportional hazard model methodology.

  4. 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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of the following tumor types

    • Non Hodgkin-lymphoma, including:

      • Diffuse large B-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 or refractory 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%
  • Have the capacity to give informed consent
  • Anticipated survival of > 3 months
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • 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
  • Receipt of prior anti PD-1 or PD-L1 therapy
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04205409

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Contact: Andrew Cowan 206.606.7348

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United States, Washington
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
University of Washington
National Cancer Institute (NCI)
Bristol-Myers Squibb
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Principal Investigator: Andrew Cowan Fred Hutch/University of Washington Cancer Consortium
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Responsible Party: University of Washington Identifier: NCT04205409    
Other Study ID Numbers: RG1005491
NCI-2019-08192 ( Registry Identifier: NCI / CTRP )
P30CA015704 ( U.S. NIH Grant/Contract )
First Posted: December 19, 2019    Key Record Dates
Last Update Posted: May 29, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Large B-Cell, Diffuse
Hematologic Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Leukemia, B-Cell
Neoplasms by Site
Antineoplastic Agents, Immunological
Antineoplastic Agents