Phase 1 Dose Finding Study of Belinostat for Treatment of Patients With Peripheral T-cell Lymphoma (PTCL)

Study Overview
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Brief Summary
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The primary objective of this study is to determine the Maximum Tolerated Dose (MTD) for belinostat when combined with CHOP regimen and establish the recommended belinostat dose for the Phase 3 study.

Detailed Description
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This is a Phase 1 dose finding study using the traditional escalation rule of 3+3 design to evaluate the Maximum Tolerated Dose (MTD) of belinostat when administered in combination with CHOP.

Official Title
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Phase 1 Dose Finding Study of Belinostat Plus Cyclophosphamide/Vincristine/Doxorubicin/Prednisone (CHOP) Regimen (BelCHOP) for Treatment of Patients With Peripheral T-cell Lymphoma(PTCL)

Conditions
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Peripheral T-cell Lymphoma

Intervention / Treatment
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* Drug: Belinostat
* Drug: CHOP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or above Life Expectancy > 3 months Histologically confirmed diagnosis of PTCL Patients with transformed CTCL eligible for CHOP regimen Measurable disease based on Cheson 2007 criteria Eastern Cooperative Oncology Group (ECOG) performance status < 2 Exclusion Criteria: Known active Hepatitis B/ Hepatitis C/ HIV infection Known, uncontrolled CNS metastases or primary CNS lymphoma Deep vein thrombosis diagnosed within 3 months Ongoing treatment for pre-existing cardiovascular disease Neuropathy Grade 3 or more Previous extensive radiotherapy except limited field RT for locally advanced nasal NK PTCL or for pain palliation Prior therapy with severely myelotoxic regimens, including autologous and allogenic stem cell transplantation Prior therapy with HDAC inhibitors (except for CTCL) Inadequate hematological, hepatic, or renal function

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Finding Phase<br>This is a Phase 1 dose finding study using the traditional escalation rule of 3+3 design to evaluate the Maximum Tolerated Dose of Belinostat when administered in combination with CHOP. In Part A of the study, up to three sequential dose cohorts will enroll a maximum of 6 patients each. Enrollment will begin with the enrollment of patients into Cohort 3. On Day 1 of each 21-day treatment cycle, the study treatment will start with belinostat followed by CHOP regimen. | Drug: Belinostat<br>* Belinostat will be administered by intravenous infusion once daily for up to 5 days depending on the dose cohort as follows: Cohort 1: belinostat 1000 mg/m2 IV on Day 1 Cohort 2: belinostat 1000 mg/m2 IV on Day 1-2 Cohort 3: belinostat 1000 mg/m2 IV on Day 1-3 Cohort 4: belinostat 1000 mg/m2 IV on Day 1-4 Cohort 5: belinostat 1000 mg/m2 IV on Day 1-5<br>* Other names: PXD101;Drug: CHOP<br>* Cyclophosphamide - 750 mg/m2 - IV - Day 1 Vincristine - 1.4 mg/m2 - IV - Day 1 Doxorubicin - 50mg/m2 - IV - Day 1 Prednisone 100mg PO - On Day 1 Prednisone will be administered after chemotherapy part of CHOP, and on Day 2-5 after belinostat.<br>* Other names: Prednisone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) | To determine the MTD for belinostat when combined with CHOP regimen and establish the Phase 3 recommended belinostat dose. | up to 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerance | To assess safety and tolerance of belinostat when given in combination with CHOP regimen. Safety and tolerance will be mainly characterized by the number and severity of treatment emergent adverse events, and treatment related AEs that occur or worsen after the first dose of study treatment. | up to 5 days | 
| Overall Response Rate | Overall response rate (ORR) after 6 cycles of BelCHOP regimen | 126 days | 
| Effectiveness of study drug | Pharmacokinetics of belinostat when co-administered with CHOP regimen. The concentration of Belinostat to assess the effectiveness. | 126 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PTCL, Maximum Tolerated Dose, Belinostat