Human IL-15 (rhIL-15) and Obinutuzumab for Relapsed and Refractory Chronic Lymphocyte Leukemia

  • STATUS
    Recruiting
  • End date
    Dec 31, 2023
  • participants needed
    24
  • sponsor
    National Cancer Institute (NCI)
Updated on 22 September 2021
cancer
lymphoid leukemia
hematologic malignancy
anemia
chronic lymphocytic leukemia
lymphoma
thrombocytopenia

Summary

Background

Chronic lymphocytic leukemia (CLL) is a blood cancer. Recombinant human interleukin 15 (IL-15) is a manmade protein. Obinutuzumab is a protein made to deactivate cancer cells. Researchers want to see if treating people with CLL with both proteins improves their outcomes.

Objectives

To find the safe dose of IL-15 with obinutuzumab. To identify its effects, including on the immune system and cancer.

Eligibility

Adults at least 18 years old who have certain CLL that standard therapy has failed

Design

Participants will be screened with:

  • Medical history
  • Physical exam
  • Evaluation of ability to do daily activities
  • Blood, heart, and urine tests

Participants may also be screened with:

  • A small amount of bone marrow removed by needle in the hipbone
  • Scans of the body and/or brain

The study will be done in 28-day cycles for up to 6 cycles.

Participants will get the study drugs through a catheter and pump.

Cycle 1: Participants will stay in the clinic for week 1. They will get:

  • IL-15 as a continuous intravenous infusion over 24 hours on days 1-5
  • Obinutuzumab as an infusion on 4 days, over about 4 hours. The doses for this will increase.

Other cycles: Participants will come to the clinic days 1 5 and get IL-15 as in cycle 1. They will get obinutuzumab on day 4.

During the study, participants:

  • Will repeat screening tests
  • Will get standard medicines for side effects
  • May give blood, saliva, and tumor samples for research

After treatment, participants will have follow-up visits every 3 months for 1 year, then every 6 months for up to 5 years. After that, participants may be called or emailed.

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 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 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.

Details
Condition Lymphocyte, leukemia, B lymphocyte, Chronic, Leukemia (Pediatric), leukemias
Treatment Obinutuzumab, rhIL-15
Clinical Study IdentifierNCT03759184
SponsorNational Cancer Institute (NCI)
Last Modified on22 September 2021

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