Nivolumab and Tocilizumab for Relapsed Hematological Malignancy Post-allogeneic Transplant
- Conditions
- Acute LeukemiaLymphomaMyelodysplastic SyndromesChronic Leukemia
- Interventions
- Registration Number
- NCT03588936
- Lead Sponsor
- Medical College of Wisconsin
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 2
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Nivolumab (0.25 mg/kg) and Tocilizumab Nivolumab (.25 mg/kg) Participant will receive tocilizumab 8 mg/kg IV (max dose 800 mg) on Day 0. On Day 1 participants will receive nivolumab IV (0.25 mg/kg based on dose escalation design). Nivolumab will be given every \~2 weeks for up to 4 doses and a second dose of Tocilizumab will be given on \~Day 29 on the same day as Dose # 3 of Nivolumab. Nivolumab (0.5 mg/kg) and Tocilizumab Nivolumab (.5 mg/kg) Participant will receive tocilizumab 8 mg/kg IV (max dose 800 mg) on Day 0. On Day 1 participants will receive nivolumab IV (0.5 mg/kg based on dose escalation design). Nivolumab will be given every \~2 weeks for up to 4 doses and a second dose of Tocilizumab will be given on \~Day 29 on the same day as Dose # 3 of Nivolumab. Nivolumab (0.5 mg/kg) and Tocilizumab Tocilizumab Participant will receive tocilizumab 8 mg/kg IV (max dose 800 mg) on Day 0. On Day 1 participants will receive nivolumab IV (0.5 mg/kg based on dose escalation design). Nivolumab will be given every \~2 weeks for up to 4 doses and a second dose of Tocilizumab will be given on \~Day 29 on the same day as Dose # 3 of Nivolumab. Nivolumab (0.25 mg/kg) and Tocilizumab Tocilizumab Participant will receive tocilizumab 8 mg/kg IV (max dose 800 mg) on Day 0. On Day 1 participants will receive nivolumab IV (0.25 mg/kg based on dose escalation design). Nivolumab will be given every \~2 weeks for up to 4 doses and a second dose of Tocilizumab will be given on \~Day 29 on the same day as Dose # 3 of Nivolumab.
- Primary Outcome Measures
Name Time Method Maximum-tolerated Dose Up to 4 weeks after last dose of study treatment (approximately 3 months) 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.
- Secondary Outcome Measures
Name Time Method Response Rates Based on Imaging End of study treatment (approximately 2 months) 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).
Progression-Free Survival Up to 1 year from beginning of treatment Determine the number of subjects alive and in remission after treatment.
Duration of response in responding participants Up to 1 year from the beginning of treatment Number of subjects with complete response or stable disease.
Response Rates Based on Pathologic Response End of study treatment (approximately 2 months) The number of subjects with bone marrow response (achievement of complete response; \<5% blasts; stable disease; progressive disease).
Overall Survival Up to 1 year from beginning of treatment The number of participants alive.
Dose-limiting toxicities Up to 4 weeks after last dose of study treatment (approximately 3 months) 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.
Trial Locations
- Locations (1)
Froedtert Hospital and the Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States