ACY-1215 + BCR Pathway Inhibitors for Chronic Lymphocytic Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Must not be taking: CYP3A4 inducers/inhibitors

Disqualifiers: Chemotherapy, Radiotherapy, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 2 years

3 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that participants stop taking any medications that strongly affect CYP3A4, a liver enzyme, at least 7 days before starting the study. If you are on such medications, you may need to stop them or switch to alternatives. It's best to discuss your current medications with the study team to see if any changes are needed.

What evidence supports the effectiveness of the drugs ACY-1215, Ibrutinib, Imbruvica, and Idelalisib for treating chronic lymphocytic leukemia?

Ibrutinib and Idelalisib, which are part of the treatment, have been shown to significantly improve survival and response rates in patients with chronic lymphocytic leukemia, although they may also increase the risk of serious side effects. ^{1 2 3 4 5}

What makes the drug combination of ACY-1215, Ibrutinib, and Idelalisib unique for treating chronic lymphocytic leukemia?

This drug combination is unique because it targets the B-cell receptor (BCR) signaling pathway, which is crucial in the development of chronic lymphocytic leukemia. Ibrutinib and Idelalisib are already known for their effectiveness in inhibiting key enzymes in this pathway, and combining them with ACY-1215 may enhance their efficacy and offer a novel approach compared to traditional treatments. ^{1 2 4 5 6}

What is the purpose of this trial?

This research study is studying a drug called ACY-1215 in combination with ibrutinib or idelalisib as a possible treatment for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL).

Research Team

Jennifer R Brown, MD, PhD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

Adults with Chronic Lymphocytic Leukemia (CLL) that has come back after at least one treatment can join this trial. They need to have certain levels of blood cells, normal organ function, and measurable disease. Participants must use birth control and not be on conflicting medications or have uncontrolled illnesses.

Inclusion Criteria

total bilirubin < 2X institutional upper limit of normal (ULN) unless predominantly indirect and therefore likely due to hemolysis or Gilbert's syndrome

creatinine < 2X ULN

The effects of the drugs studied in this research protocol on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of treatment administration

Exclusion Criteria

Participants who are receiving any other investigational agents

I haven't had chemotherapy or radiotherapy in the last 2 weeks and have recovered from any side effects.

I have been treated with an HDAC inhibitor before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ACY-1215 in combination with either Ibrutinib or Idelalisib, administered orally continuously in 28-day cycles

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• ACY-1215
• Ibrutinib
• Idelalisib

Trial Overview The study is testing ACY-1215 combined with either Ibrutinib or Idelalisib in patients whose CLL has relapsed. The goal is to see if these combinations are effective as a new treatment option for CLL.

Participant Groups

Group I: Combination of ACY-1215 With Idelalisib Experimental Treatment 2 Interventions

ACY-1215 and Idelalisib will be administered orally continuously, with 28 consecutive days arbitrarily defined as a treatment cycle. The dose level will be predetermine.

Group II: Combination of ACY-1215 With Ibrutinib Experimental Treatment 2 Interventions

ACY-1215 and Ibrutinib will be administered orally continuously, with 28 consecutive days arbitrarily defined as a treatment cycle. The dose level will be predetermine.

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Acetylon Pharmaceuticals Incorporated

Industry Sponsor

Trials

4

Recruited

60+

Findings from Research

Ibrutinib and idelalisib, two inhibitors targeting the B-cell receptor pathway, are effective treatments for B-cell malignancies like chronic lymphatic leukaemia and mantle cell lymphoma, with established roles as first-line therapies for specific patient groups.

While these agents show promise, their combination with other treatments can lead to unexpected toxicities, highlighting the need for careful evaluation of risks and benefits in treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting of B-cell receptor signalling in B-cell malignancies. Jerkeman, M., Hallek, M., Dreyling, M., et al.[2021]

Ibrutinib is a targeted therapy specifically designed for treating chronic lymphocytic leukemia (CLL), which is a type of cancer that affects the blood and bone marrow.

This novel treatment works by inhibiting Bruton's tyrosine kinase (BTK), a key enzyme that helps cancer cells survive and proliferate, leading to improved patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib (imbruvica): a novel targeted therapy for chronic lymphocytic leukemia. Parmar, S., Patel, K., Pinilla-Ibarz, J.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of B-cell receptor signaling pathway inhibitors in relapsed/refractory chronic lymphocytic leukemia: a systematic review and meta-analysis of randomized clinical trials. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Targeting B Cell Signaling in Chronic Lymphocytic Leukemia. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

The Real-World Experience With Single Agent Ibrutinib in Relapsed/Refractory CLL. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Targeting of B-cell receptor signalling in B-cell malignancies. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Ibrutinib (imbruvica): a novel targeted therapy for chronic lymphocytic leukemia. [2021]

6. China pubmed.ncbi.nlm.nih.gov

[Reaserch Advance on Inhibitor Targeting at the B-Cell Receptor Pathway in Chronic Lymphocytic Leukemia --Review]. [2020]