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

Sponsor

University of Washington (Other)

Overall Status

Recruiting

CT.gov ID

NCT04205409

Collaborator

Bristol-Myers Squibb (Industry)

Enrollment

Location

Arm

37.8

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

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.

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 Recurrent Mantle Cell Lymphoma Refractory Mantle Cell Lymphoma	Biological: Nivolumab	Phase 2

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 Design

Study Type:

Interventional

Anticipated 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

Actual Study Start Date :

Jun 5, 2020

Anticipated Primary Completion Date :

Aug 1, 2023

Anticipated Study Completion Date :

Aug 1, 2023

Arms and Interventions

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 CMAB819 Nivolumab Biosimilar CMAB819

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

CMAB819

Nivolumab Biosimilar CMAB819

Outcome Measures

Primary Outcome Measures

Best overall response rate (ORR) [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

Overall survival [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 [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 [Up to 5 years]
Will employ Kaplan-Meier and Cox proportional hazard model methodology.
Incidence of adverse events [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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