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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with Chronic Lymphocytic Leukemia (CLL) that has returned or not responded to previous treatments. It combines the experimental drug ACY-1215 with either ibrutinib (Imbruvica) or idelalisib to evaluate the effectiveness of this combination. Participants should have CLL requiring further treatment and must have undergone at least one prior therapy. Those with recent bleeding issues or who need blood thinners may not qualify for the ibrutinib group. The study aims to find a more effective way to manage CLL for those unsuccessful with earlier treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that ibrutinib is safe for treating chronic lymphocytic leukemia (CLL). Most people tolerate it well, experiencing manageable side effects like diarrhea, tiredness, and some bleeding. Long-term research also supports its safety for many patients.

Idelalisib is another treatment option that has proven effective and safe, whether used alone or with other drugs for relapsed CLL. Common side effects include diarrhea, fever, and liver issues, but these are usually mild.

ACY-1215 is a newer drug that early studies have shown to be well-tolerated when combined with other cancer treatments. It appears safe, with mild side effects like tiredness and nausea.

This trial examines the safety of using ACY-1215 with either ibrutinib or idelalisib. Although the study is in its early stages, existing research on each drug suggests a promising safety outlook when used together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination treatments involving ACY-1215 with either Ibrutinib or Idelalisib for chronic lymphocytic leukemia (CLL) because they target cancer cells in a unique way. Unlike standard treatments that primarily focus on blocking the BCR pathway alone, these combinations also inhibit histone deacetylase (HDAC) with ACY-1215, potentially enhancing the effectiveness of BCR inhibitors. This dual-action approach not only aims to disrupt cancer cell growth more effectively but also hopes to overcome resistance seen with current therapies. By combining these mechanisms, the treatment could provide a more comprehensive strategy against CLL, offering hope for improved patient outcomes.

What evidence suggests that this trial's treatments could be effective for Chronic Lymphocytic Leukemia?

Research has shown that ibrutinib, one of the treatments in this trial, effectively treats chronic lymphocytic leukemia (CLL) and can surpass standard treatments for some patients. It also reduces the need for doctor visits related to the disease, resulting in fewer clinic trips. Idelalisib, another treatment option in this trial, has proven effective for CLL that has returned or is unresponsive to other treatments, especially when combined with rituximab. After 24 weeks, 93% of patients taking both idelalisib and rituximab did not experience disease progression. ACY-1215, administered in this trial with either ibrutinib or idelalisib, is generally well tolerated and can help control lymphoma, suggesting its usefulness when combined with other treatments. These findings support the potential benefits of using ACY-1215 with either ibrutinib or idelalisib for treating CLL. ^{1 2 4 6 7}

Who Is on the Research Team?

Jennifer R Brown, MD, PhD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7153674/

Efficacy of Ibrutinib-Based Regimen in Chronic ... Ibrutinib has shown to have better efficacy than standard chemoimmunotherapy in del17 positive chronic lymphocytic leukemia (CLL) patients; however its role ...

2. jnj.com jnj.com/innovativemedicine/emea/imbruvicarvibrutinib-combination-therapy-data-two-studies-and-long-term-integrated-analysis

Imbruvica®▼(ibrutinib) Combination Therapy Data ... Imbruvica®▽(ibrutinib) Combination Therapy Data From Two Studies and Long-Term Integrated Analysis Presented at ASH 2019 Show Efficacy and ...

3. becarispublishing.com becarispublishing.com/doi/10.57264/cer-2024-0210

A comparison of healthcare resource utilization and costs ... A study found that patients with CLL/SLL treated with ibrutinib had fewer disease-related outpatient visits and similar or lower healthcare costs.

4. withpower.com withpower.com/trial/acy-1215-bcr-pathway-inhibitors-for-chronic-lymphocytic-leukemia-d2674

ACY-1215 + BCR Pathway Inhibitors for Chronic ... 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 ...

5. dana-farber.org dana-farber.org/clinical-trials/15-558

A Phase Ib Study of ACY-1215 in Combination with BCR ... This research study is studying a drug called ACY-1215 in combination with ibrutinib or idelalisib as a possible treatment for Relapsed or Refractory ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11971162/

Final results on effectiveness and safety of Ibrutinib in patients ... We conducted an observational study (FIRE) to understand the effectiveness and safety outcomes of ibrutinib in patients with chronic lymphocytic leukemia (CLL) ...

7. imbruvicahcp.com imbruvicahcp.com/cll/safety/pooled-long-term-safety

Pooled Long-Term Safety | IMBRUVICA® (ibrutinib) HCP Find the long-term safety and tolerability profile from IMBRUVICA® (ibrutinib) CLL/SLL studies. See Full Prescribing & Safety Information.