Human IL-15 (rhIL-15) and Obinutuzumab for Relapsed and Refractory Chronic Lymphocyte Leukemia
Last updated on July 2021Recruitment
- Recruitment Status
- Recruiting
- Estimated Enrollment
- Same as current
Summary
- Conditions
- B Cell
- Chronic
- Leukemia
- Lymphocytic
- Type
- Interventional
- Phase
- Phase 1
- Design
- Allocation: N/AIntervention Model: Sequential AssignmentMasking: None (Open Label)Primary Purpose: Treatment
Participation Requirements
- Age
- Between 18 years and 125 years
- Gender
- Both males and females
Description
Background: Of the several drugs and drug combinations approved for treatment of relapsed and refractory chronic lymphocytic leukemia (CLL), the reported complete response rates are no greater than 30%. Obinutuzumab is a glycoengineered, humanized type 2 anti-CD20 monoclonal antibody thought to enga...
Background: Of the several drugs and drug combinations approved for treatment of relapsed and refractory chronic lymphocytic leukemia (CLL), the reported complete response rates are no greater than 30%. Obinutuzumab is a glycoengineered, humanized type 2 anti-CD20 monoclonal antibody thought to engage the immune system by directly activating antibody-dependent, cellmediated cytotoxicity (ADCC); it is approved for treatment of chronic lymphocytic leukemia in combination with chlorambucil. The key mediators of ADCC are polymorphonuclear neutrophils, monocytes, and natural killer (NK) cells. Recombinant human Interleukin-15 (rhIL-15) is a stimulatory cytokine that promotes the differentiation and activation of NK cells, monocytes, and long-term CD8+ memory Tcells. In a Phase I trial, administration of rhIL-15 as a 5-day continuous intravenous infusion (civ) was associated with up to 45-fold increase in the number of NK cells at well tolerated dose levels. Preclinical murine lymphoid malignancy models have shown increased efficacy of monoclonal antibodies when administered together with rhIL-15; BL/6 mice inoculated with EL4-CD20 cells (a syngeneic lymphoma line); including significant prolongation of survival with the IL-15/Rituximab combination compared to either drug given as single agent (90% v. 30% alive at 75 days). Objectives: - To determine the safety, toxicity profile, dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of civ rhIL-15 administration in combination with intravenous (IV) obinutuzumab treatment Eligibility: Age greater than or equal to 18 years old ECOG performance status less than or equal to 1 Diagnosis of chronic lymphocytic leukemia (CLL) with greater than or equal to 50% of B cells xpressing CD20 Patients must have measurable or evaluable disease Patients must have CLL that is refractory or relapsed following therapy with a Bruton s tyrosine kinase (BTK) inhibitor OR have relapsed/refractory CLL and are intolerant to ibrutinib therapy; patients with del(17p) must also be refractory or relapsed after, or intolerant to BTK inhibitor therapy; patients with del(17p) must also be refractory or relapsed after, or intolerant to, therapy with venetoclax Adequate organ function parameters as defined within the protocol Active disease requiring treatment, as defined within the protocol Design: This is a single institution non-randomized Phase I dose escalation study evaluating increasing doses of civ rhIL-15 in combination with obinutuzumab using a standard 3 + 3 dose escalation design. On days 1-5 of each 4-week cycle, rhIL-15 will be administered by civ at dose levels 0.5, 1, and 2 mcg/kg/day. During the first cycle, obinutuzumab will be administered at a dose of 100 mg by IV on day 4, 900 mg on day 5, 1,000 mg on day 11, and 1,000 mg on day 18; then 1,000 mg on day 4 of each subsequent cycle. Infusion reaction, antimicrobial, and tumor lysis syndrome prophylaxis will be administered per manufacturer s recommendations. Treatment will continue up to 6 cycles, or until unacceptable toxicity or progressive disease. Up to 24 patients will be enrolled in the study.
Tracking Information
- NCT #
- NCT03759184
- Collaborators
- Not Provided
- Investigators
- Principal Investigator: Milos Miljkovic, M.D. National Cancer Institute (NCI)