Duvelisib + Romidepsin/Bortezomib for T-Cell Lymphoma

Not currently recruiting at 14 trial locations

Overseen By Steven M. Horwitz, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Antivirals, Anti-arrhythmics

Disqualifiers: Pregnancy, HIV, Hepatitis, Heart disease, others

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety of a drug called duvelisib for treating T-cell lymphoma, a type of cancer affecting white blood cells. Participants will receive duvelisib (also known as Copiktra) alongside either romidepsin or bortezomib (also known as Velcade) to evaluate how these combinations work together. The trial seeks individuals with T-cell lymphoma that has returned or worsened after at least one treatment. It may suit those who have undergone at least one previous treatment for T-cell lymphoma and are experiencing disease progression. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Do I have to stop taking my current medications for the trial?

You will need to stop any previous systemic anti-cancer therapy at least 3 weeks before starting the trial. If you are on corticosteroids, short courses must be stopped at least 6 days before the trial, but stable ongoing use of low-dose corticosteroids is allowed. For other medications, the protocol does not specify, so it's best to discuss with the trial team.

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

Research has shown that combining duvelisib and romidepsin effectively treats patients with relapsed peripheral T-cell lymphoma. The safety profile of this combination aligns with earlier studies, indicating it is generally well-tolerated.

Early results for the duvelisib and bortezomib combination suggest that duvelisib is reasonably safe for patients with T-cell lymphomas. Duvelisib has approval for other similar conditions, supporting its safety. However, as this trial is in an early stage, researchers continue to study safety carefully, and the data remains incomplete.

Overall, while both treatment combinations appear promising, they are still under safety evaluation in this trial. Participants might experience side effects common with cancer treatments, but ongoing research aims to better understand these effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments involving duvelisib combined with romidepsin or bortezomib for T-cell lymphoma because they offer new mechanisms of action compared to standard therapies like chemotherapy and stem cell transplants. Duvelisib is a PI3K inhibitor that targets specific pathways in cancer cells, potentially leading to more effective results with fewer side effects. Romidepsin, delivered intravenously, is a histone deacetylase inhibitor that can slow cancer cell growth, while bortezomib, given as a subcutaneous injection, disrupts cancer cell protein recycling. These innovative approaches could provide more precise and effective treatment options for patients with T-cell lymphoma.

What evidence suggests that this trial's treatments could be effective for T-Cell Lymphoma?

This trial will study two different treatment combinations for T-cell lymphomas. Research has shown that combining duvelisib and romidepsin, one of the treatment arms in this trial, may help treat relapsed or hard-to-treat peripheral T-cell lymphoma. Specifically, studies found that 58% of patients responded to this combination, with 42% showing no detectable signs of cancer afterward, suggesting significant effectiveness for some individuals. Meanwhile, the combination of duvelisib and bortezomib, another treatment arm in this trial, is also under evaluation. Although less information exists about this combination, duvelisib has proven effective in treating similar conditions. Overall, these combinations are being studied for their potential benefits in treating T-cell lymphomas. ^{1 6 7 8 9}

Who Is on the Research Team?

Steven M. Horwitz, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults over 18 with relapsed or refractory T-cell lymphomas, including stage ≥ Ib CTCL, after at least one systemic therapy. Participants must have certain blood counts and organ function levels, no serious medical conditions that would prevent consent, not be pregnant or breastfeeding, agree to use birth control, and have measurable disease.

Inclusion Criteria

Meet the following laboratory criteria without use of growth factor support or platelet transfusions for 1 week: i) Absolute neutrophil count ≥ 1.0 K/mcl, ii) Platelet count ≥ 80 K/μl (in the expansion cohorts, if thrombocytopenia is due to bone marrow involvement platelet count must be ≥ 50 K/μL), iii) Patients enrolled in the dose escalation phase who are not enrolled on the expansion cohorts must have calculated creatinine clearance ≥ 50ml/min by Cockcroft-Gault formula. Patients enrolled in the Dose Expansion phase must have calculated creatinine clearance ≥ 40ml/min by Cockcroft-Gault formula, iv) Total bilirubin ≤ 1.5 x upper limit of normal (ULN) or ≤ 3 x ULN if documented hepatic involvement with lymphoma, or ≤ 5 x ULN if history of Gilbert's syndrome; AST (SGOT) and ALT (SGPT) ≤ 3 x ULN; ≤ 5 ULN if due to lymphoma involvement

Women of reproductive potential† must have a negative serum or urine β human chorionic gonadotropin (βhCG) pregnancy test. All women of reproductive potential, all sexually active male patients, and all partners of patients must agree to use adequate methods of birth control (e.g. latex condoms) throughout the study and for 30 days after the last dose of study drug

My T-cell lymphoma has worsened after at least one treatment.

Exclusion Criteria

I am receiving or have received therapy to prevent cancer recurrence, not for T-cell lymphoma.

Patients with positive hepatitis C virus Ab

Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Standard 3+3 dose escalation to determine the maximum tolerated dose (MTD) of duvelisib with romidepsin and duvelisib with bortezomib

1 cycle (28 days)

Visits on Days 1, 8, 15 for Romidepsin arm; Days 1, 4, 8, 11 for Bortezomib arm

Cohort Expansion

Further assess toxicity and safety, and allow a preliminary assessment of the efficacy of the combination

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bortezomib
• Duvelisib
• Romidepsin

Trial Overview The trial is testing the safety of duvelisib in combination with either romidepsin or bortezomib for treating T-cell lymphomas. It's looking at how well these drug combinations work when previous treatments haven't been successful.

How Is the Trial Designed?

Group I: Romidepsin + duvelisib Experimental Treatment 2 Interventions

Romidepsin/duvelisib: Cycle 1 and beyond Days 1, 8, 15\* Romidepsin IVPB over 4 hours, days 1, 8, 15 duvelisib by mouth twice daily, days 1-28

Group II: Bortezomib + duvelisib Experimental Treatment 2 Interventions

Bortezomib/duvelisib: Cycle 1 and beyond Days 1, 4, 8, and 11\* Bortezomib subcutaneous injection, days 1, 4, 8, 11\*\* duvelisib by mouth twice daily, days 1-28

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

Approved in European Union as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in United States as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Canada as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Japan as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Dana-Farber Cancer Institute

Collaborator

Trials

1,128

Recruited

382,000+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02783625

Study Details | NCT02783625 | Trial of Duvelisib in ... The phase I portion of the study is designed to determine the MTD of duvelisib with romidepsin and duvelisib with bortezomib.

2. onclive.com onclive.com/view/duvelisib-plus-romidepsin-displays-activity-in-r-r-ptcl

Duvelisib plus Romidepsin Displays Activity in R/R PTCL The combination of duvelisib plus romidepsin was shown to be highly active in patients with relapsed/peripheral T-cell lymphoma.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11862811/

Duvelisib plus Romidepsin in relapsed/refractory T cell ... Nevertheless, the combination of romidepsin and duvelisib shows substantial promise for the treatment of T-cell lymphomas. The data from this study establishing ...

4. investor.verastem.com investor.verastem.com/news-releases/news-release-details/verastem-oncology-presents-copiktratm-duvelisib-data-peripheral

Verastem Oncology Presents COPIKTRA™ (Duvelisib) Data in ... COPIKTRA is indicated for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma ( ...

5. bloodcancerstoday.com bloodcancerstoday.com/post/phase-ib-iia-trial-compares-duvelisib-plus-romidepsin-or-bortezomib-for-t-cell-lymphoma

Phase Ib/IIa Trial Compares Duvelisib Plus Romidepsin or ... Patients with relapsed or refractory T-cell lymphoma (TCL) had a higher tolerance of duvelisib when it was combined with romidepsin versus bortezomib and also ...

6. investor.verastem.com investor.verastem.com/node/11481/pdf

Verastem Oncology Presents COPIKTRA™ (Duvelisib) Data in ... 1,2,3 COPIKTRA is indicated for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic ...

7. cancernetwork.com cancernetwork.com/view/duvelisib-plus-romidepsin-yields-high-results-in-relapsed-refractory-peripheral-t-cell-lymphoma

Duvelisib Plus Romidepsin Yields High Results in ... A positive overall response rate was achieved when patients with relapsed/refractory peripheral T-cell lymphoma were treated with duvelisib plus romidespin.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7517780/

A Review of PI3K Inhibitors in B-Cell Malignancies - PMC Duvelisib is being evaluated in combination with venetoclax (Venclexta) for relapsed or refractory CLL/SLL and in peripheral T-cell lymphoma (NCT03534323, ...

9. targetedonc.com targetedonc.com/view/duvelisib-gains-fda-orphan-drug-designation-for-tcell-lymphomas

Duvelisib Gains FDA Orphan Drug Designation for T-Cell ... The preliminary safety profile for duvelisib was considered reasonable in patients with peripheral T-cell lymphomas and was thought to be ...