Clinical Trials /

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

NCT04205409

Description:

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.

Related Conditions:
  • Chronic Lymphocytic Leukemia
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
  • Marginal Zone Lymphoma
  • Multiple Myeloma
  • Non-Hodgkin Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab for the Treatment of Relapsed or Refractory Hematologic Malignancies
  • Official Title: Nivolumab for Relapsed or Refractory Disease Post Chimeric Antigen Receptor T-Cell Treatment in Patients With Hematologic Malignancies

Clinical Trial IDs

  • ORG STUDY ID: RG1005491
  • SECONDARY ID: NCI-2019-08192
  • SECONDARY ID: P30CA015704
  • NCT ID: NCT04205409

Conditions

  • 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

Interventions

DrugSynonymsArms
Nivolumab946414-94-4, BMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoTreatment (nivolumab)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (nivolumab)ExperimentalPatients receive nivolumab IV over 30 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Nivolumab

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Best overall response rate (ORR)
Time Frame:Up to 5 years
Safety Issue:
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.

Secondary Outcome Measures

Measure:Overall survival
Time Frame:From the first study drug administration to death from any cause, up to 5 years
Safety Issue:
Description:Will employ Kaplan-Meier and Cox proportional hazard model methodology.
Measure: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
Safety Issue:
Description:Will employ Kaplan-Meier and Cox proportional hazard model methodology.
Measure:Duration of response
Time Frame:Up to 5 years
Safety Issue:
Description:Will employ Kaplan-Meier and Cox proportional hazard model methodology.
Measure:Incidence of adverse events
Time Frame:Up to 30 days after the last dose of study drug
Safety Issue:
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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Washington

Last Updated

December 17, 2019