Duvelisib + BMS-986345 for Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must be taking: Entecavir

Must not be taking: CYP3A4 inhibitors, CYP3A inducers

Disqualifiers: CNS lymphoma, HIV, Hepatitis B, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug combination for individuals with certain types of lymphoma, a cancer affecting the immune system. The goal is to determine a safe dose and assess how well participants tolerate the combination of two drugs, BMS-986345 and duvelisib (also known as Copiktra, an oral medication). It is suitable for those who have tried other lymphoma treatments without success and have no other viable options. Participants should have a measurable tumor and should not have recently undergone a stem cell transplant or certain other treatments. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug combination.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you cannot take certain medications like potent CYP3A4 inhibitors or inducers within 14 days before starting the study treatment. It's best to discuss your current medications with the trial team to see if any need to be adjusted.

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

Research has shown that duvelisib, one of the treatments in this trial, raised safety concerns in past studies. Specifically, it posed a higher risk of death and serious side effects compared to another cancer medicine. While duvelisib can be effective, it requires careful monitoring due to these potential risks.

Regarding BMS-986345, limited public information exists on its safety because the study involving it remains in an early stage. Early-stage studies typically focus on determining the safest dose and assessing how well participants tolerate the treatment.

In summary, duvelisib presents known risks that require monitoring, and BMS-986345 is still under study to evaluate its safety. Participants should consider these factors when deciding whether to join the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Duvelisib with BMS-986345 for lymphoma because this treatment approach could offer a new way to tackle the disease. Most treatments for lymphoma focus on disrupting the growth of cancer cells through traditional chemotherapy or monoclonal antibodies. However, Duvelisib is a PI3K inhibitor, targeting specific proteins involved in cancer cell survival, while BMS-986345 is being tested to enhance this effect by working in tandem with Duvelisib. This combination aims to improve effectiveness and potentially reduce the progression of the disease, offering hope for better outcomes compared to existing therapies.

What evidence suggests that this trial's treatments could be effective for lymphoma?

Research has shown that duvelisib, a pill, yields promising results in treating certain blood cancers like lymphoma. In studies, duvelisib effectively targeted cancer in patients who had already received multiple treatments. It blocks specific proteins that aid cancer cell growth. This trial tests the combination of duvelisib with BMS-986345 to determine if it can safely and effectively treat lymphoma. While the effectiveness of BMS-986345 remains under study, combining it with duvelisib might enhance its efficacy. ^{6 7 8 9 10}

Who Is on the Research Team?

Hayder Saeed, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

Adults with certain types of lymphoid malignancies, including various T-cell lymphomas and B-cell lymphomas, who have progressed after prior therapies. Participants must be over 18, have a performance status indicating they can carry out daily activities with little or no assistance, and not be pregnant or planning to conceive. They should also have adequate organ function.

Inclusion Criteria

Willingness to avoid pregnancy or fathering children based on the following criteria

I have been diagnosed with a specific type of lymphoma or leukemia.

I am fully active or can carry out light work.

Exclusion Criteria

History of serious allergic reactions including anaphylaxis and toxic epidermal necrolysis

I cannot take preventive treatments for pneumocystis or herpes viruses.

I haven't had major heart problems or a heart attack in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Dose escalation to determine the maximum tolerated dose (MTD) of BMS-986345 in combination with Duvelisib in patients with lymphoid malignancy

Up to 26 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 26 months

What Are the Treatments Tested in This Trial?

Interventions

• CC-486
• Duvelisib

Trial Overview The trial is testing the safety and optimal dose of BMS-986345 when used in combination with duvelisib for treating specific lymphoid cancers. It aims to determine how well patients tolerate this drug combo.

How Is the Trial Designed?

Group I: Dose Escalation Experimental Treatment 2 Interventions

Dose escalation to determine the maximum tolerated dose (MTD) of BMS-986345 in combination with Duvelisib in patients with lymphoid malignancy. Patients will be treated in cohorts of size three to six and the dosage will be escalated if the clinical toxicity is acceptable. A total of 6 dose levels will be used.

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Secura Bio, Inc.

Industry Sponsor

Trials

9

Recruited

200+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30742566/

A Phase II Study of Duvelisib (IPI-145) in Patients With ... In the DYNAMO study, oral duvelisib monotherapy demonstrated clinically meaningful activity and a manageable safety profile in heavily pretreated, ...

2. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2018/211155Orig1Orig2s000MultidisciplineR.pdf

211155Orig1s000 211155Orig2s000 - accessdata.fda.gov The pivotal evidence of effectiveness comes from the efficacy results in Study-IPI-145-07 and Study IPI-145-06. Is the proposed dosing ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6220789/

Duvelisib, an oral dual PI3K‐δ, γ inhibitor, shows clinical ... Duvelisib demonstrated favorable clinical activity and an acceptable safety profile in these high‐risk, heavily pretreated, relapsed/refractory iNHL patients.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.18.00915

DYNAMO: A Phase II Study of Duvelisib (IPI-145) in ... In the DYNAMO study, oral duvelisib monotherapy demonstrated clinically meaningful activity and a manageable safety profile in heavily pretreated, double- ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02049515

A Phase 3 Extension Study of Duvelisib and Ofatumumab ... A Phase 3 (extension) clinical trial to examine the efficacy of IPI-145 (duvelisib) monotherapy or ofatumumab monotherapy in participants with chronic ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05065866

Duvelisib in Combination With BMS-986345 in Lymphoid ... The purpose of the study is to find a safe dose and to evaluate the safety and tolerability of the drug BMS-986345, in combination with duvelisib. Official ...

7. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3065/533780/A-Phase-I-Study-of-Duvelisib-in-Combination-with

A Phase I Study of Duvelisib in Combination with Oral ... A Phase I Study of Duvelisib in Combination with Oral Azacitidine (BMS-986345) in Mature T Cell Lymphoma Available ... lymphoma (RR TCL) is a poor ...

8. withpower.com withpower.com/trial/phase-1-lymphoma-8-2021-19d98

Duvelisib + BMS-986345 for Lymphoma · Info for Participants Trial Overview The trial is testing the safety and optimal dose of BMS-986345 when used in combination with duvelisib for treating specific lymphoid cancers. It ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12395046/

Real-world evidence of duvelisib and romidepsin in relapsed ... A previous phase 1/2 study of duvelisib/romidepsin (duv/romi) reported an overall response rate (ORR) of 58% and a complete response rate (CRR) of 42% with ...

10. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05065866/duvelisib-in-combination-with-bms-986345-in-lymphoid-malignancy

Duvelisib in Combination With BMS-986345 in Lymphoid ... The purpose of the study is to find a safe dose and to evaluate the safety and tolerability of the drug BMS-986345, in combination with ...