This is a phase 1, interventional single arm, open label, treatment study designed to evaluate the safety combination programmed cell death protein 1 (PD-1) and interleukin 6 (IL-6) inhibition in participants with relapsed disease post-allogeneic transplant.
Study disease: Hematologic malignancies including, but not exclusive to,acute/chronic leukemia, lymphoma, and myelodysplastic syndrome that has relapsed after allogeneic transplant. Study Rationale: Phase 1 Safety/Dose Finding Study: To determine the safety and maximum tolerated dose of Nivolumab in combination with Tocilizumab. Study Agent Description: Tocilizumab is a monoclonal antibody and immunosuppressant; specifically, tocilizumab is an IL-6 receptor antagonist. Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that binds to the PD-1 receptor of T cells blocking its interaction with PD-L1 and PD-L2, thereby enhancing T-cell proliferation and allowing the immune system to attack the tumor. Number of Subjects: A maximum of 12 participants will be enrolled on this Phase 1 study. Duration of Follow-up: Participants will be followed for up to one year post-treatment for survival and response. Study Design: This is a 3 + 3 design. In a "3 + 3 design," three participants are initially enrolled into a given dose cohort. If there is no dose limiting toxicity (DLT) observed in any of these subjects, the trial proceeds to enroll additional subjects into the next higher dose cohort. If one subject develops a DLT at a specific dose, an additional three subjects are enrolled into that same dose cohort. Development of DLTs in more than one of six subjects in a specific dose cohort suggests that the maximum tolerated dose (MTD) has been exceeded, and further dose escalation is not pursued.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
2
Participants will receive Nivolumab at one of two dose levels every 2 weeks for 4 treatments.
Participants will receive 2 doses of tocilizumab
Participants will receive Nivolumab at one of two dose levels every 2 weeks for 4 treatments.
Froedtert Hospital and the Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Maximum-tolerated Dose
Determine the safety and the maximum tolerated dose among two candidate doses of nivolumab in combination with tocilizumab for treatment of relapsed hematological malignancy post-allogeneic transplant. Maximum-tolerated dose is based on the determination of dose-limiting toxicities.
Time frame: Up to 4 weeks after last dose of study treatment (approximately 3 months)
Response Rates Based on Imaging
The number of subjects with stable disease as evidenced by imaging (Diagnostic positron emission tomography (PET)-CT scans or CT of the neck, chest, abdomen, and pelvis).
Time frame: End of study treatment (approximately 2 months)
Response Rates Based on Pathologic Response
The number of subjects with bone marrow response (achievement of complete response; \<5% blasts; stable disease; progressive disease).
Time frame: End of study treatment (approximately 2 months)
Overall Survival
The number of participants alive.
Time frame: Up to 1 year from beginning of treatment
Progression-Free Survival
Determine the number of subjects alive and in remission after treatment.
Time frame: Up to 1 year from beginning of treatment
Duration of response in responding participants
Number of subjects with complete response or stable disease.
Time frame: Up to 1 year from the beginning of treatment
Dose-limiting toxicities
The number of subjects with dose-limiting toxicities. This will be measured by the number of adverse events as defined by the NCI CTCAE version 4.03 non-hematologic ≥ grade 3-5 signs/symptoms or by the development of steroid refractory grade 2-4 graft-versus-host disease or severe chronic graft-versus-host disease.
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Time frame: Up to 4 weeks after last dose of study treatment (approximately 3 months)