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

• Sponsor: Acrotech Biopharma LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01839097
• Collaborator: (none)
• Enrollment: 23
• Locations: 8
• Arm: 1
• Duration (Months): 32
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Peripheral T-cell Lymphoma	Drug: Belinostat; Drug: CHOP	Phase 1

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Study Start Date: May 1, 2013
• Actual Primary Completion Date: Jan 1, 2016
• Actual Study Completion Date: Jan 1, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Dose Finding Phase 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; 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; Other Names: PXD101 ; Drug: CHOP; 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.; Other Names: Cyclophosphamide Vincristine Doxorubicin Prednisone

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose (MTD) [up to 5 days]

   To determine the MTD for belinostat when combined with CHOP regimen and establish the Phase 3 recommended belinostat dose.

Secondary Outcome Measures

1. Safety and tolerance [up to 5 days]

   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.

2. Overall Response Rate [126 days]

   Overall response rate (ORR) after 6 cycles of BelCHOP regimen

3. Effectiveness of study drug [126 days]

   Pharmacokinetics of belinostat when co-administered with CHOP regimen. The concentration of Belinostat to assess the effectiveness.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale University	New Haven	Connecticut	United States	06511
2	Northeast Georgia Cancer Care, LLC	Athens	Georgia	United States	30607
3	Mayo Clinic	Rochester	Minnesota	United States	55905
4	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
5	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
6	Hematology - Oncology Associates of Northern NJ P.A	Morristown	New Jersey	United States	07962
7	Columbia University Medical Center/Center for Lymphiod Malignancies	New York	New York	United States	10019
8	Duke University Medical Center	Durham	North Carolina	United States	27705

Sponsors and Collaborators

• Acrotech Biopharma LLC

Investigators

• Study Director: Mi Rim Choi, MD, Spectrum Pharmaceuticals, Inc

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Acrotech Biopharma LLC
• ClinicalTrials.gov Identifier: NCT01839097
• Other Study ID Numbers: SPI-BEL-12-104
• First Posted: Apr 24, 2013
• Last Update Posted: Jan 3, 2020
• Last Verified: Dec 1, 2019

• Keywords provided by Acrotech Biopharma LLC: PTCL; Maximum Tolerated Dose; Belinostat
• Additional relevant MeSH terms: Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Prednisone; Cyclophosphamide; Doxorubicin; Vincristine; Belinostat

Study Results

No Results Posted as of Jan 3, 2020