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

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ClinicalTrials.gov Identifier: NCT04205409
Recruitment Status : Not yet recruiting
First Posted : December 19, 2019
Last Update Posted : May 29, 2020
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Bristol-Myers Squibb
Information provided by (Responsible Party):
University of Washington

Tracking Information
First Submitted Date  ICMJE December 17, 2019
First Posted Date  ICMJE December 19, 2019
Last Update Posted Date May 29, 2020
Estimated Study Start Date  ICMJE June 4, 2020
Estimated Primary Completion Date August 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 17, 2019)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 17, 2019)
  • 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.
  • 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.
  • Duration of response [ Time Frame: Up to 5 years ]
    Will employ Kaplan-Meier and Cox proportional hazard model methodology.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Nivolumab for Relapsed or Refractory Disease Post Chimeric Antigen Receptor T-cell Treatment in Patients With Hematologic Malignancies
Official Title  ICMJE Nivolumab for Relapsed or Refractory Disease Post Chimeric Antigen Receptor T-Cell Treatment in Patients With Hematologic Malignancies
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE Biological: Nivolumab
Given IV
Other Names:
  • 946414-94-4
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
Study Arms  ICMJE 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.
Intervention: Biological: Nivolumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: December 17, 2019)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 1, 2022
Estimated Primary Completion Date August 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Andrew Cowan 206.606.7348 ajcowan@seattlecca.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04205409
Other Study ID Numbers  ICMJE RG1005491
NCI-2019-08192 ( Registry Identifier: NCI / CTRP )
P30CA015704 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Washington
Study Sponsor  ICMJE University of Washington
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • Bristol-Myers Squibb
Investigators  ICMJE
Principal Investigator: Andrew Cowan Fred Hutch/University of Washington Cancer Consortium
PRS Account University of Washington
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP