Belinostat + Zidovudine for Adult T-Cell Lymphoma

Overseen By Karin Suarez

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Miami

Must be taking: Erythropoietin, G-CSF

Must not be taking: Investigational agents

Disqualifiers: Progressive disease, Chronic leukemia, Uncontrolled illness, others

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

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

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 combination of two drugs, Belinostat (a chemotherapy) and Zidovudine (an antiretroviral medication), to treat adult T-cell lymphoma (ATLL), a rare blood cancer. The goal is to determine if these drugs, when combined, can better manage the disease after initial treatments. Individuals with ATLL who have previously received treatments like AZT/IFNα therapy or chemotherapy and have shown some improvement may be suitable for this trial. The trial targets those who still exhibit signs of the disease in their blood and are confirmed to have the HTLV-1 viral infection. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are taking investigational agents, you must stop them 14 days before starting the study, unless you are on certain types of interferon, which are allowed.

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

Research has shown that using Belinostat with Zidovudine (AZT) may help treat adult T-cell leukemia-lymphoma. In earlier studies, most patients tolerated this combination well. Some experienced mild side effects like tiredness or nausea, which are common with many cancer treatments. No serious side effects were consistently reported.

Belinostat is already approved for treating another type of cancer, indicating a well-understood safety profile. Zidovudine, also known as AZT, has been used for many years to treat HIV/AIDS, further supporting its safety record.

Overall, evidence suggests that the combination of Belinostat and Zidovudine is generally well-tolerated. As always, participants should discuss any concerns with their doctor before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Belinostat and Zidovudine for Adult T-Cell Lymphoma because it offers a novel approach by combining a histone deacetylase inhibitor with an antiretroviral drug. Current treatments often focus on chemotherapy and antiviral therapies separately, but this combo targets cancer cells through epigenetic modification, potentially making them more susceptible to existing antiviral strategies. Additionally, the potential inclusion of Interferon-Alfa-2b as an optional component could enhance immune response, providing a multi-pronged attack against the disease. This integrative strategy could lead to more effective consolidation and maintenance therapy, offering hope for improved outcomes.

What evidence suggests that Belinostat + Zidovudine could be an effective treatment for adult T-cell lymphoma?

Research has shown that the combination of Belinostat with Zidovudine (AZT), under study in this trial, may help treat Adult T-Cell Leukemia-Lymphoma (ATLL). This combination appears particularly beneficial for patients with more severe forms of the disease. Belinostat can stop cancer cells from growing, and when used with AZT, it has effectively managed ATLL symptoms. Early results suggest this treatment could be a valuable option for those facing this challenging condition. ^{1 2 3 5 6}

Who Is on the Research Team?

Juan C Ramos, MD

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

Adults with Adult T-Cell Leukemia-Lymphoma (ATLL) who have had some treatment and a partial response can join. They must be over 18, have certain blood counts and liver/kidney function, not be pregnant or breastfeeding, agree to use birth control, and cannot have other serious health issues or another active cancer.

Inclusion Criteria

Creatinine clearance (CrCl) ≥ 40 mL/min

HIV+ patients eligible

I have been diagnosed with aggressive adult T-cell leukemia/lymphoma.

Exclusion Criteria

I do not have any other active cancers.

Conditions likely to interfere with study requirements/treatment

My liver issues are not caused by lymphoma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Consolidation Therapy

Participants receive Belinostat in combination with Zidovudine (AZT) as consolidation therapy

Up to 3 months

Maintenance Therapy

Participants receive standard Zidovudine (AZT)-based maintenance therapy with optional Interferon-Alfa-2b or Pegylated Interferon-Alfa-2b

Up to 9 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Belinostat
• Zidovudine

Trial Overview The trial is testing Belinostat combined with Zidovudine as a follow-up therapy for ATLL. Participants will already have received some treatment for ATLL and shown improvement without new disease progression.

How Is the Trial Designed?

Group I: Belinostat + Zidovudine Experimental Treatment 4 Interventions

Belinostat + Zidovudine (AZT) in combination as consolidation therapy, followed by standard zidovudine (AZT)-based maintenance therapy with optional Interferon-Alfa-2b (IFNalfa-2b) or Pegylated Interferon-Alfa-2b (PEG-IFN-alfa-2b)

Who Is Running the Clinical Trial?

University of Miami

Lead Sponsor

Trials

976

Recruited

423,000+

Published Research Related to This Trial

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]

The FDA has granted accelerated approval for Beleodaq, a histone deacetylase inhibitor, specifically for patients with relapsed or refractory peripheral T-cell lymphoma.

This approval indicates that Beleodaq has shown promising efficacy in treating this type of lymphoma, which is important for patients who have not responded to previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beleodaq approved for rare lymphomas. [2014]

Citations

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Belinostat Therapy With Zidovudine for Adult T-Cell ... The investigators propose to use Belinostat in combination with AZT as consolidation therapy for the treatment of ATLL. Official Title. A Phase II Trial of ...

2. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/9448/488540/Safety-and-Efficacy-of-Belinostat-Trial-with

Safety and Efficacy of Belinostat Trial with Zidovudine Plus ... Safety and Efficacy of Belinostat Trial with Zidovudine Plus Interferon for HTLV-1 Related Adult T-Cell Leukemia-Lymphoma: Interim Results ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124044677

Safety and Efficacy of AZT-Interferon-α with Belinostat (AI- ... AI-BEL can be efficacious in patients with aggressive ATL with circulating leukemic cells. Our results demonstrate that judicious use of HDAC inhibitors in ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6494249/

Revised Adult T-Cell Leukemia-Lymphoma International ... Preclinical efficacy of belinostat in combination with zidovudine in adult T-cell leukemia-lymphoma. Retrovirology. 2015;12(suppl 1):P73. [Google Scholar] ...

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Belinostat Therapy With Zidovudine for Adult T-Cell Leukemia A phase of research to describe clinical trials that gather more information about a drug's safety and effectiveness by studying different populations and ...

6. scholarship.miami.edu scholarship.miami.edu/esploro/outputs/journalArticle/Safety-and-Efficacy-of-Belinostat-Trial/991031785739102976

Safety and Efficacy of Belinostat Trial with Zidovudine Plus ... Safety and Efficacy of Belinostat Trial with Zidovudine Plus Interferon for HTLV-1 Related Adult T-Cell Leukemia-Lymphoma: Interim Results.