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
To find the safe dose of IL-15 with obinutuzumab. To identify its effects, including on the
immune system and cancer.
Adults at least 18 years old who have certain CLL that standard therapy has failed
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
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.
- 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).
- 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)
- 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
- 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
- Up to 24 patients will be enrolled in the study.