Belinostat Therapy With Zidovudine for Adult T-Cell Leukemia-Lymphoma

NCT02737046 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 20150567
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators propose to use Belinostat in combination with AZT as consolidation therapy for the treatment of ATLL.

Conditions

Adult T-cell Leukemia-Lymphoma; ATLL

Outcome Measures

Primary Outcomes (2)

• Number of Participants Achieving Complete Molecular Response in Blood Compartment (CMR)

  Number of participants achieving Complete Molecular Response after receiving protocol therapy will be reported. Complete Molecular Response (CMR) is defined as the disappearance of malignant clone(s), as proven by negative T-cell receptor gene rearrangement studies of peripheral blood DNA and bone marrow. CMR will be evaluated based upon T-cell clonality studies to be conducted while subjects are on Belinostat, and while subjects are receiving Zidovudine (AZT)-based maintenance treatment (after Belinostat completion).

  From end of cycle 3 until at least end of month 12

• Number of Participants Experiencing Treatment-Related Serious Adverse Events and Adverse Events

  Number of participants experiencing treatment-related serious adverse events (SAEs), and adverse events (AEs). SAEs and AEs will be assessed by and assigned severity and treatment attribution using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03.

  Up to 13 months

Secondary Outcomes (6)

• Number of Participants Achieving Clinical Response

  Up to 12 months

• Failure-Free Survival (FFS) Rate at 12 Months Using Kaplan-Meier Method

  12 months

• Overall Survival (OS) Rate at 12 Months Using Kaplan-Meier Method

  12 months

• Number of Participants Exhibiting Disruption of HTLV-1 Latency in Vivo

  Up to 13 months

• Number of Participants Exhibiting Cytotoxic T-Cell Response in Vivo

  Up to 13 months

Study Arms (1)

Belinostat + Zidovudine

EXPERIMENTAL

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)

Drug: Belinostat; Drug: Zidovudine; Drug: Interferon-Alfa-2b; Drug: Pegylated Interferon-Alfa-2b; Drug: Lymphodepleting Therapy

Interventions

Belinostat DRUG

Belinostat will be administered as 1,000 mg/m2 IV infusion over 30 minutes on Days 1- 5 every 21 days (Exception as per FDA-approved Package Insert: In patients known to be homozygous for the UGT1A1\*28 allele, the starting belinostat dose must be 750mg/m2) for up to 8 cycles.

Also known as: PXD101, Beleodaq®

Belinostat + Zidovudine

Zidovudine DRUG

Zidovudine shall be administered in the outpatient setting as 300 mg tablets orally (PO), three times daily (TID) for 21 days on cycles 1 to 8, followed by maintenance therapy (+/- IFN-alfa) up to the end of Month 12.

Also known as: AZT

Belinostat + Zidovudine

Interferon-Alfa-2b DRUG

OPTIONAL: For subjects receiving interferon therapy at baseline, continue Interferon alfa-2b 5 million IU daily or pegylated interferon alfa-2b 1.5 μg/kg once weekly, subcutaneously (SQ) for up to 12 months.

Also known as: IFN-α-2b

Belinostat + Zidovudine

Pegylated Interferon-Alfa-2b DRUG

OPTIONAL: For subjects receiving interferon therapy at baseline, continue Interferon alfa-2b 5 million IU daily or pegylated interferon alfa-2b 1.5 μg/kg once weekly, subcutaneously (SQ) for up to 12 months.

Also known as: PEG-IFN-α-2b

Belinostat + Zidovudine

Lymphodepleting Therapy DRUG

OPTIONAL: For subjects with any increase in lymphocyte count. Cyclophosphamide administered as 375 mg/m2 via intravenous infusion once during Cycle 1 after Day 5 of Belinostat therapy.

Also known as: Cyclophosphamide

Belinostat + Zidovudine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically documented adult T-cell leukemia/lymphoma (ATLL) with the following characteristics:
• Any stage of disease,
• Aggressive types (for definition of ATLL subtypes see Appendix H),
• Documented presence of ATLL cells in peripheral blood by either morphology, histology, flow cytometry or gene rearrangement studies.
• One of the following:
• Initiated AZT/IFNα therapy prior or at the time of enrollment. OR;
• Received chemotherapy or other antineoplastic drug therapy ≥ 2 weeks prior to enrollment with the exception of dose-reduced vincristine/and or cyclophosphamide, or high dose steroids, administered for cytoreductive purpose. (Note: Continuation of zidovudine and interferon therapy is allowed.).
• Presence of ATLL based on morphology, histology, flow cytometry, or T-cell clonality in peripheral blood during screening period prior enrollment.
• Documented Human T-cell lymphotropic virus type 1 (HTLV-1) infection: Documentation may be serologic assay (ELISA) confirmed by Western blot or polymerase chain reaction (PCR).
• Measurable or evaluable disease, including presence of ATLL by immunophenotyping from either histology or flow cytometry studies, or molecular disease as evidence by T-cell clonality detected by gene rearrangement studies.
• years of age or older.
• Karnofsky performance status (KPS) ≥ 50% or Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3
• Patients must have adequate end organ and bone marrow function as defined below:
• absolute neutrophil count (ANC) ≥ 1,000 cells/mm3 \[Exception: Unless cytopenias are secondary to ATLL\]
• platelets (PLT) ≥ 50,000 cells/mm3 \[Exception: Unless cytopenias are secondary to ATLL\]

You may not qualify if:

• Patients with progressive disease (after previous chemotherapy or AZT/IFNα) at the time of enrollment.
• Patients with chronic leukemia with favorable features, or smoldering type ATLL.
• Patients receiving any other investigational agents within 14 days prior to initiation of study therapy. (Exception: Patients actively receiving IFN-alfa-2b, PEG-IFN-alfa-2b, or similar forms of IFN-alfa are permitted).
• Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (CHF), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that are likely in the judgment of the Investigator(s) to interfere or limit compliance with study requirements/treatment.
• Pregnant or breast-feeding women.
• Known hypersensitivity to histone deacetylases (HDACs), zidovudine, belinostat or any component of the formulation(s).
• Acute hepatitis or decompensated liver disease unless due to lymphoma. Chronic hepatitis will be required to be on prophylactic treatment during the study if provided liver function test meet criteria listed above without evidence of cirrhosis to be eligible.
• Concurrent active malignancies, with the exception of in situ carcinoma of the cervix, non-metastatic, non-melanomatous skin cancer, or Kaposi's sarcoma not requiring systemic chemotherapy.
• Known New York Heart Association (NYHA) Class 3 or 4 heart disease as per Appendix D.
• Known ejection fraction \< 45% or institutional limit of normal range
• Psychological, familial, sociological or geographical conditions likely in the judgment of the Investigator(s) to interfere or limit compliance with study requirements/treatment.

Sponsors & Collaborators

• University of Miami: lead

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

Location

MeSH Terms

Conditions

Leukemia-Lymphoma, Adult T-Cell

Interventions

belinostat; Zidovudine; Introns; peginterferon alfa-2b; Cyclophosphamide

Condition Hierarchy (Ancestors)

Leukemia, T-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; DNA, Intergenic; Genome Components; Genome; Genetic Structures; Genetic Phenomena; Gene Components; Genes; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Juan Carlos Ramos MD
• Organization: University of Miami

jramos2@med.miami.edu

305-243-4860

Study Officials

• Juan C Ramos, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 10, 2016
• First Posted: April 13, 2016
• Study Start: December 12, 2016
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2025
• Last Updated: March 10, 2026
• Results First Posted: March 10, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)