Triple Therapy for Chronic Lymphocytic Leukemia

Overseen By Nitin Jain, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must be taking: Ibrutinib

Must not be taking: Warfarin, Strong CYP3A inhibitors

Disqualifiers: Autoimmune diseases, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 8

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of three drugs to help patients with chronic lymphocytic leukemia (CLL) and Richter transformation (RT). The drugs work by boosting the immune system to fight cancer and stopping cancer cells from growing.

Research Team

Nitin Jain, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults with chronic lymphocytic leukemia (CLL) or Richter transformation (RT), who have had prior treatments for CLL or are untreated with high-risk features, can join. They must be in good general health based on specific blood tests and agree to use effective contraception. Excluded are those with severe lung disease, certain heart conditions, uncontrolled hypertension, active infections, hepatitis B/C or HIV, recent major surgery or other cancer treatments.

Inclusion Criteria

Patients or their legally authorized representative must provide written informed consent

I have CLL or SLL that didn't respond to or came back after treatment, or I haven't been treated but have high-risk genetics.

Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotrophin (beta-human chorionic gonadotropin [hCG]) pregnancy test result within 14 days prior to the first dose of treatment and must agree to use an effective contraception method during the study and for 23 weeks following the last dose of the study drugs. Females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy. Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 31 weeks following the last dose of study drugs

Exclusion Criteria

Patients who have uncontrolled hypertension (defined as sustained systolic blood pressure >= 140 mmHg or diastolic >= 90 mmHg)

Patient is pregnant or breast-feeding

You are currently using an experimental drug for treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Patients receive ipilimumab IV over 90 minutes on day 1 and ibrutinib PO QD. Treatment repeats every 3 weeks for up to 4 cycles.

12 weeks

4 visits (in-person)

Treatment Part B

Patients receive ipilimumab IV over 90 minutes, nivolumab IV over 30 minutes on day 1, and ibrutinib PO QD starting day 7. Treatment repeats every 3 weeks for up to 4 cycles.

12 weeks

4 visits (in-person)

Extension

Patients who benefit from treatment may continue ipilimumab every 12 weeks and nivolumab every 4 weeks for up to 2 years.

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

30 days, then every 3 months

Treatment Details

Interventions

• Ibrutinib
• Ipilimumab
• Nivolumab

Trial Overview The trial is testing the combination of ipilimumab (an immune system booster) with ibrutinib alone or together with nivolumab for treating CLL and RT. It aims to find the safest dose that works best by seeing how these drugs affect cancer growth.

Participant Groups

Group I: Part B (ipilimumab, nivolumab, ibrutinib) Experimental Treatment 3 Interventions

Patients receive ipilimumab IV over 90 minutes and nivolumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning day 7 of cycle 1, patients also receive ibrutinib PO QD in the absence of disease progression or unacceptable toxicity. Patients who complete 4 doses of ipilimumab and nivolumab, and are deriving benefit from it, without severe toxicities, may continue to receive ipilimumab every 12 weeks and nivolumab every 4 weeks for up to a total of 2 years.

Group II: Part A (ipilimumab, ibrutinib) Experimental Treatment 2 Interventions

Patients receive ipilimumab IV over 90 minutes on day 1. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning day 1 of cycle 1, patients also receive ibrutinib PO QD in the absence of disease progression or unacceptable toxicity. Patients who complete 4 doses of ipilimumab and are deriving benefit from it, without severe toxicities, may continue to receive ipilimumab every 12 weeks for up to a total of 2 years.

Ibrutinib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in United States as Imbruvica for:

• Chronic lymphocytic leukemia/small lymphocytic lymphoma
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in Canada as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma

Approved in Japan as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+