Clinical trial NCT02737046: Belinostat Therapy With Zidovudine for Adult T-Cell Leukemia-Lymphoma
Official title: A Phase II Trial of Belinostat as Consolidation Therapy With Zidovudine for Adult T-Cell Leukemia-Lymphoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Adult T-cell Leukemia-Lymphoma
ATLL
Lead sponsor: University of Miami
Sponsor class: OTHER
First posted: 2016-04-13
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


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.

Primary outcomes:
measure: Proportion of Participants achieving Complete Molecular Response (CMR)
timeFrame: From End of Cycle 3 to End of Maintenance Therapy, Up to 12 Months
measure: Proportion of Participants with Minimal Residual Disease (MRD)
timeFrame: From End of Cycle 3 to End of Maintenance Therapy, Up to 12 Months
measure: Proportion of Participants Experiencing Treatment-Related Serious Adverse Events and Adverse Events
timeFrame: Up to 13 months
Secondary outcomes:
measure: Rate of Participants Achieving Clinical Response
timeFrame: Up to 12 months
measure: One Year Rate of Failure-Free Survival (FFS)
timeFrame: Up to 24 months
measure: One Year Rate of Overall Survival (OS)
timeFrame: Up to 24 months
measure: Proportion of participants exhibiting a cytotoxic T-cell response
timeFrame: Up to 13 months
measure: HTLV-1 pro-viral load
timeFrame: Up to 13 months
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
Study officials:
affiliation: University of Miami
name: Juan C Ramos, MD
role: PRINCIPAL_INVESTIGATOR
References: