Recruitment

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)