Belinostat/Pralatrexate + CHOP for T-Cell Lymphoma

(CRESCENDO Trial)

Recruiting at 30 trial locations

Overseen By Uma Atmuri

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Acrotech Biopharma Inc.

Must not be taking: UGT1A1 inhibitors, HDAC inhibitors

Disqualifiers: Precursor T-cell lymphoma, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 9

Duration: 18 weeks

504 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for people with T-cell lymphoma, a type of blood cancer. Researchers aim to find the best drug combination to prevent the cancer from worsening. The trial compares two new drug combinations, including Belinostat (also known as Beleodaq or PXD101) and Pralatrexate (also known as Folotyn), with an existing treatment to determine which is most effective. Individuals newly diagnosed with T-cell lymphoma who have not yet received treatment may be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer treatment advancements.

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

If you are taking drugs that are potent UGT1A1 inhibitors, you must stop them one week before joining the trial. You can start them again if your treatment doesn't include belinostat. 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?

Previous studies tested the combination of belinostat with CHOP for safety. The results suggested that patients managed this combination well, as they did not experience severe side effects, indicating its safety.

Similarly, the combination of pralatrexate with COP also demonstrated promising safety results. Research indicates that patients new to PTCL treatment tolerated this combination well. Like belinostat, patients did not reach a dose that caused severe side effects, supporting its safety.

Both treatments have shown safety for patients, with manageable side effects. These findings help ensure that the treatments are well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for T-cell lymphoma because they combine belinostat and pralatrexate with the well-known CHOP regimen, potentially enhancing effectiveness. Belinostat is a histone deacetylase inhibitor, which may help make cancer cells more sensitive to chemotherapy. Pralatrexate, on the other hand, is a folate analog metabolic inhibitor that disrupts cancer cell growth by interfering with DNA synthesis. These innovative combinations aim to improve outcomes beyond the standard CHOP regimen by leveraging new mechanisms to target the cancer more precisely.

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

Research has shown that adding belinostat to CHOP chemotherapy might improve treatment results for peripheral T-cell lymphoma (PTCL). In this trial, some participants will receive belinostat combined with CHOP. Previous studies found that belinostat works in PTCL, suggesting it could enhance the effectiveness of standard chemotherapy.

Other participants will receive pralatrexate combined with COP. Studies have shown that combining pralatrexate with CHOP achieved an overall response rate (ORR) of 83.9% in patients newly diagnosed with PTCL. This suggests pralatrexate might be highly effective in treating PTCL when used with chemotherapy. Both treatments show promise in helping people with PTCL live longer without disease progression. ^{1 2 3 4 5}

Who Is on the Research Team?

Uma Srinivas Atmuri, MPharm, MS

Principal Investigator

Acrotech Biopharma Inc.

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed Peripheral T-cell Lymphoma (PTCL) who have not been treated before. They must be in good physical condition, with adequate blood counts and liver/kidney function. Patients should agree to use two forms of contraception and cannot participate if they have certain other lymphomas, uncontrolled conditions like high blood pressure or infections, are pregnant/breastfeeding, or have used experimental treatments recently.

Inclusion Criteria

My immune cells show a TFH phenotype.

My condition is a specific type of T-cell lymphoma.

My UGT1A1 gene has been tested.

Exclusion Criteria

I have been diagnosed with a specific condition.

I have adult T-cell lymphoma/leukemia.

My cancer is a type of lymphoma that affects the skin.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive up to 6 cycles of treatment with either Bel-CHOP, Fol-COP, or CHOP alone, with cycles repeated every 21 days

18 weeks

6 cycles, each with multiple visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, with tumor assessments every 3 months for 3 years, then every 6 months

5 years

Regular follow-up visits every 3 months for 3 years, then every 6 months

Long-term survival follow-up

Long-term follow-up for overall survival analysis, conducted by phone every 6 months

8 years

What Are the Treatments Tested in This Trial?

Interventions

• Belinostat
• CHOP
• COP
• Pralatrexate

Trial Overview The study tests the effectiveness of Belinostat or Pralatrexate when combined with CHOP/COP chemotherapy against CHOP alone in PTCL patients. It's a two-part study: first to find safe doses and then to compare how well each treatment prevents cancer progression over up to six cycles of therapy.

How Is the Trial Designed?

Group I: Group 2a Active Control 2 Interventions

Group 2a Pralatrexate 20 mg/m2 + COP

Group II: Group 3 Active Control 1 Intervention

CHOP

Group III: Group 1a Active Control 2 Interventions

Group 1a Belinostat 600 mg/m2 + CHOP

Group IV: Group 1b Active Control 2 Interventions

Group 1b Belinostat 1000 mg/m2 + CHOP

Group V: Group 2b Active Control 2 Interventions

Group 2b Pralatrexate 30 mg/m2 + COP

Belinostat is already approved in United States for the following indications:

Approved in United States as Beleodaq for:

• Peripheral T-cell lymphoma (PTCL)

Who Is Running the Clinical Trial?

Acrotech Biopharma Inc.

Lead Sponsor

Trials

31

Recruited

5,200+

Published Research Related to This Trial

The combination of pralatrexate (PLX) and belinostat (BLS) showed an additive effect in various lymphoma cell lines, indicating that they can work together effectively to inhibit cancer cell growth.

BLS significantly increased the sensitivity of lymphoma cells to PLX, suggesting that using BLS could enhance the efficacy of PLX treatment, particularly in B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Schedule-Dependent Synergy Between the Histone Deacetylase Inhibitor Belinostat and the Dihydrofolate Reductase Inhibitor Pralatrexate in T-and B-cell Lymphoma Cells in vitro. Peters, GJ., van Gemert, FPA., Kathmann, I., et al.[2020]

Belinostat is an effective treatment for relapsed or refractory peripheral T-cell lymphoma (PTCL), showing an overall response rate of 25.8% and a median duration of response of 8.4 months in clinical trials.

The treatment is generally well tolerated, with common side effects including nausea, vomiting, fatigue, pyrexia, and anemia, affecting more than 25% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belinostat for the treatment of relapsed or refractory peripheral T-cell lymphoma. Campbell, P., Thomas, CM.[2017]

In a study involving 23 patients with previously untreated peripheral T-cell lymphoma, the combination of belinostat and CHOP was well tolerated, with the maximum tolerated dose (MTD) established at 1000 mg/m2 over a Day 1-5 schedule.

The treatment showed a high overall response rate (ORR) of 86%, with 71% of patients achieving a complete response (CR) at the MTD, indicating its efficacy in treating this type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belinostat in combination with standard cyclophosphamide, doxorubicin, vincristine and prednisone as first-line treatment for patients with newly diagnosed peripheral T-cell lymphoma. Johnston, PB., Cashen, AF., Nikolinakos, PG., et al.[2021]

Belinostat, a histone deacetylase inhibitor, received accelerated FDA approval for treating relapsed or refractory peripheral T-cell lymphoma (PTCL) based on a trial involving 120 patients, showing an overall response rate of 25.8%.

The treatment demonstrated a median duration of response of 8.4 months, with common side effects including nausea and fatigue, and notable grade 3/4 toxicities such as anemia and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval: Belinostat for the Treatment of Patients with Relapsed or Refractory Peripheral T-cell Lymphoma. Lee, HZ., Kwitkowski, VE., Del Valle, PL., et al.[2015]

Anthracycline-containing regimens like CHOP are the standard first-line treatment for peripheral T-cell lymphoma, but many patients either do not respond or relapse quickly, highlighting the need for new treatment options.

New agents such as pralatrexate, romidepsin, belinostat, and brentuximab vedotin have been approved for relapsed cases, but they do not significantly improve survival rates; ongoing research is exploring their combination with CHOP to enhance treatment efficacy and increase transplant eligibility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peripheral T-cell lymphoma, not otherwise specified. Broccoli, A., Zinzani, PL.[2021]

Belinostat shows promise as a treatment for relapsed/refractory peripheral T-cell lymphomas, which typically have limited effective therapies.

In a case involving a young patient with angioimmunoblastic-type lymphoma, treatment with belinostat followed by allogeneic stem cell transplantation resulted in a complete hematologic response that has lasted over 2 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete hematologic response after belinostat treatment and allogeneic stem cell transplantation for multiple relapsed/refractory angioimmunoblastic T-cell lymphoma: A case report. Camus, V., Etancelin, P., Drieux, F., et al.[2023]

Belinostat is a small-molecule inhibitor that targets multiple classes of histone deacetylase enzymes and has been specifically developed for treating relapsed or refractory peripheral T-cell lymphoma (PTCL).

It has received accelerated approval from the FDA as a monotherapy for PTCL, marking a significant milestone in its development and offering a new treatment option for patients with this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belinostat: first global approval. Poole, RM.[2021]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3123.1/529160/Trial-in-Progress-A-Phase-3-Randomized-Open-Label

Trial in Progress: A Phase 3, Randomized, Open-Label Study ... We describe the Phase 3 CRESCENDO trial, designed to determine if adding either Fol or Bel to first-line chemotherapy improves outcomes in newly diagnosed PTCL.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4530372/

Belinostat in patients with refractory or relapsed peripheral T ... The outcome of frontline chemotherapy regimens has been disappointing, with reported long-term survival of only 20–30% [Hamadani et al. 2014]. In one of the ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06072131

NCT06072131 | To Evaluate Efficacy of Belinostat or ... This is a 5 Arm study primarily to determine the best dose out of the two dose levels of Belinostat and Pralatrexate combined with CHOP/COP in newly diagnosed ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124093078

Trial in Progress: A Phase 3, Randomized, Open-Label ... We describe the Phase 3 CRESCENDO trial, designed to determine if adding either Fol or Bel to first-line chemotherapy improves outcomes in newly diagnosed PTCL.

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/hon.70096_857

857 | A PHASE 3, RANDOMIZED, OPEN‐LABEL STUDY ... Background: Pralatrexate (Fol) and belinostat (Bel) have demonstrated monotherapy activity in peripheral T-cell lymphoma (PTCL) and are ...