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

Primary Purpose

Recurrent Chronic Lymphocytic Leukemia, Recurrent Diffuse Large B-Cell Lymphoma, Recurrent Follicular Lymphoma

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Nivolumab
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Chronic Lymphocytic Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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%
  • 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
  • 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

Sites / Locations

  • Fred Hutch/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (nivolumab)

Arm Description

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

Outcomes

Primary Outcome Measures

Best overall response rate (ORR)
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

Overall survival
Will employ Kaplan-Meier and Cox proportional hazard model methodology.
Progression-free survival
Will employ Kaplan-Meier and Cox proportional hazard model methodology.
Duration of response
Will employ Kaplan-Meier and Cox proportional hazard model methodology.
Incidence of adverse events
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.

Full Information

First Posted
December 17, 2019
Last Updated
September 11, 2023
Sponsor
University of Washington
Collaborators
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT04205409
Brief Title
Nivolumab for Relapsed, Refractory, or Detectable Disease Post Chimeric Antigen Receptor T-cell Treatment in Patients With Hematologic Malignancies
Official Title
Nivolumab for Relapsed or Refractory Disease Post Chimeric Antigen Receptor T-Cell Treatment in Patients With Hematologic Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 5, 2020 (Actual)
Primary Completion Date
February 1, 2024 (Anticipated)
Study Completion Date
August 1, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Washington
Collaborators
Bristol-Myers Squibb

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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, Recurrent Mantle Cell Lymphoma, Refractory Mantle Cell Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (nivolumab)
Arm Type
Experimental
Arm Description
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 Type
Biological
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
946414-94-4, BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo, CMAB819, Nivolumab Biosimilar CMAB819
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Best overall response rate (ORR)
Description
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.
Time Frame
Up to 5 years
Secondary Outcome Measure Information:
Title
Overall survival
Description
Will employ Kaplan-Meier and Cox proportional hazard model methodology.
Time Frame
From the first study drug administration to death from any cause, up to 5 years
Title
Progression-free survival
Description
Will employ Kaplan-Meier and Cox proportional hazard model methodology.
Time Frame
From first study drug administration to the first occurrence of disease progression or death from any cause, assessed up to 5 years
Title
Duration of response
Description
Will employ Kaplan-Meier and Cox proportional hazard model methodology.
Time Frame
Up to 5 years
Title
Incidence of adverse events
Description
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.
Time Frame
Up to 30 days after the last dose of study drug

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew Cowan
Organizational Affiliation
Fred Hutch/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutch/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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