Belinostat/Pralatrexate + CHOP for T-Cell Lymphoma

(CRESCENDO Trial)

Recruiting at30 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Acrotech Biopharma Inc.

Must not be taking: UGT1A1 inhibitors, HDAC inhibitors

Disqualifiers: Precursor T-cell lymphoma, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing two new drugs, Belinostat and Pralatrexate, combined with standard chemotherapy in patients with newly diagnosed PTCL. The goal is to find the safest and most effective dose. The new drugs work by either blocking cancer cell growth or tricking cancer cells into absorbing a harmful substance. Pralatrexate is a specially designed drug with greater preclinical antitumor activity than methotrexate.

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.

What data supports the effectiveness of the drug combination Belinostat/Pralatrexate + CHOP for T-Cell Lymphoma?

Belinostat has shown effectiveness in treating relapsed or refractory peripheral T-cell lymphoma with a response rate of 25.8% and is generally well tolerated. Additionally, the combination of Belinostat and Pralatrexate has shown promise in laboratory studies, where Belinostat increased the sensitivity of lymphoma cells to Pralatrexate, suggesting potential benefits when used together. ^{1 2 3 4 5}

Is the combination of Belinostat and Pralatrexate safe for humans?

Belinostat and Pralatrexate have been studied for safety in treating peripheral T-cell lymphoma, with common side effects including nausea, fatigue, fever, and anemia. Serious side effects can include low blood cell counts and pneumonia, but they are generally well tolerated in patients with relapsed or refractory lymphoma. ^{1 2 3 6 7}

What makes the Belinostat/Pralatrexate + CHOP drug unique for T-cell lymphoma?

This drug combination is unique because it includes belinostat, a histone deacetylase inhibitor, which can enhance the effectiveness of pralatrexate, a chemotherapy drug, by making cancer cells more sensitive to treatment. This combination aims to improve response rates and potentially allow more patients to undergo successful stem cell transplants. ^{1 2 3 4 7}

Research Team

Uma Srinivas Atmuri, MPharm, MS

Principal Investigator

Acrotech Biopharma Inc.

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Belinostat (Histone Deacetylase Inhibitor)
• CHOP (Chemotherapy)
• COP (Chemotherapy)
• Pralatrexate (Antifolate)

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.

Participant Groups

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

Who Is Running the Clinical Trial?

Acrotech Biopharma Inc.

Lead Sponsor

Trials

31

Recruited

5,200+

Findings from Research

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]

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]

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, 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]

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]

References

1. Switzerland 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. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Belinostat for the treatment of relapsed or refractory peripheral T-cell lymphoma. [2017]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Belinostat: first global approval. [2021]

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

Peripheral T-cell lymphoma, not otherwise specified. [2021]

5. England 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. [2023]

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

FDA Approval: Belinostat for the Treatment of Patients with Relapsed or Refractory Peripheral T-cell Lymphoma. [2015]

7. England 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. [2021]