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

NCT ID: NCT02737046

Last Updated: 2025-09-02

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-12
• Study Completion Date: 2025-12-31

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Belinostat + Zidovudine

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)

Group Type: EXPERIMENTAL

Belinostat

Intervention Type: 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.

Zidovudine

Intervention Type: 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.

Interferon-Alfa-2b

Intervention Type: 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.

Pegylated Interferon-Alfa-2b

Intervention Type: 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.

Interventions

Belinostat

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.

Intervention Type: DRUG

Zidovudine

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.

Intervention Type: DRUG

Interferon-Alfa-2b

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.

Intervention Type: DRUG

Pegylated Interferon-Alfa-2b

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.

Intervention Type: DRUG

Other Intervention Names

PXD101; Beleodaq®; AZT; IFN-α-2b; PEG-IFN-α-2b

Eligibility Criteria

Inclusion Criteria

1. 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.

2. One of the following:

• Received prior AZT/IFNα therapy for ≥ 2 weeks and achieved at least partial hematological response defined as > 50% reduction in absolute lymphocyte count) without evidence of new disease lesions or disease progression (defined as 50% increase in measurable disease from nadir as in section 14.5 if imaging is performed) at the time of enrollment. OR;
• Received chemotherapy for ≥ 2 weeks prior, followed by at least a partial hematologic response ((defined as > 50% reduction in absolute lymphocyte count), and without evidence of new disease lesions or disease progression (defined as 50% increase in absolute lymphocyte count or measurable disease from nadir as specified in section 14.5 if imaging is performed) at the time of enrollment. OR;
• Received high-dose steroids (prednisone, methylprednisolone, or dexamethasone) followed by at least a stable partial hematologic response without evidence of new disease lesions or disease progression (defined as 50% increase in absolute lymphocyte count or measurable disease from nadir as specified in section 14.5 if imaging is performed) within 2 weeks of enrollment.

3. Presence of residual ATLL in peripheral blood either by morphology, histology, flow cytometry or gene rearrangement studies (T-cell clonality) during screening prior to enrollment.

4. 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).

5. Measurable or evaluable disease, including presence of molecular disease as evidence by T-cell clonality detected by gene rearrangement studies.

6. 18 years of age or older.

7. Karnofsky performance status (KPS) ≥ 50% or Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3

8. 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]
• Adequate hepatic function:

• transaminase ≤ 2.5 the institutional upper limit of normal (ULN),
• total bilirubin ≤ 1.5 x the institutional upper limit of normal (ULN), [Exception: Unless secondary to hepatic infiltration with lymphoma. If the elevated bilirubin is felt to be secondary to Indinavir or Atazavinir therapy (or anti-HIV medications), patients will be allowed to enroll.]
• Creatinine clearance (CrCl) ≥ 40 mL/min, [Exception: Unless secondary to renal involvement by lymphoma is suspected.]

9. Patients who are human immunodeficiency virus positive (HIV+) are also eligible.

10. Females of childbearing potential (CBP) must have a negative serum pregnancy test within one week of enrollment. Women should avoid pregnancy while receiving study treatment. Males and females must agree to use adequate birth control during participation in this trial and for 3 months after completing therapy.

11. Patients receiving erythropoietin or Granulocyte-colony stimulating factor (G-CSF) from baseline are eligible.

Exclusion Criteria

1. Patients with progressive disease (after previous chemotherapy or AZT/IFNα) at the time of enrollment.

2. Patients with chronic leukemia with favorable features, or smoldering type ATLL.

3. 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).

4. 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.

5. Pregnant or breast-feeding women.

6. Known hypersensitivity to histone deacetylases (HDACs), zidovudine, belinostat or any component of the formulation(s).

7. 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.

8. 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.

9. Known New York Heart Association (NYHA) Class 3 or 4 heart disease as per Appendix D.

10. Known ejection fraction < 45% or institutional limit of normal range

11. Psychological, familial, sociological or geographical conditions likely in the judgment of the Investigator(s) to interfere or limit compliance with study requirements/treatment.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Miami

OTHER

Sponsor Role: lead

Responsible Party

Juan C. Ramos, MD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Juan C Ramos, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

University of Miami

Miami, Florida, United States

Countries

United States

Other Identifiers

20150567

Identifier Type: -

Identifier Source: org_study_id