Phase 1 Dose Finding Study of Belinostat for Treatment of Patients With Peripheral T-cell Lymphoma (PTCL)
Primary Purpose
Peripheral T-cell Lymphoma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Belinostat
CHOP
Sponsored by
About this trial
This is an interventional treatment trial for Peripheral T-cell Lymphoma focused on measuring PTCL, Maximum Tolerated Dose, Belinostat
Eligibility Criteria
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
Sites / Locations
- Yale University
- Northeast Georgia Cancer Care, LLC
- Mayo Clinic
- Washington University School of Medicine
- John Theurer Cancer Center at Hackensack University Medical Center
- Hematology - Oncology Associates of Northern NJ P.A
- Columbia University Medical Center/Center for Lymphiod Malignancies
- Duke University Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Dose Finding Phase
Arm Description
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.
Outcomes
Primary Outcome Measures
Maximum Tolerated Dose (MTD)
To determine the MTD for belinostat when combined with CHOP regimen and establish the Phase 3 recommended belinostat dose.
Secondary Outcome Measures
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.
Overall Response Rate
Overall response rate (ORR) after 6 cycles of BelCHOP regimen
Effectiveness of study drug
Pharmacokinetics of belinostat when co-administered with CHOP regimen. The concentration of Belinostat to assess the effectiveness.
Full Information
NCT ID
NCT01839097
First Posted
April 9, 2013
Last Updated
December 31, 2019
Sponsor
Acrotech Biopharma Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01839097
Brief Title
Phase 1 Dose Finding Study of Belinostat for Treatment of Patients With Peripheral T-cell Lymphoma (PTCL)
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 Type
Interventional
2. Study Status
Record Verification Date
December 2019
Overall Recruitment Status
Completed
Study Start Date
May 2013 (undefined)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
January 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Acrotech Biopharma Inc.
4. Oversight
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peripheral T-cell Lymphoma
Keywords
PTCL, Maximum Tolerated Dose, Belinostat
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dose Finding Phase
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Belinostat
Other Intervention Name(s)
PXD101
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
CHOP
Other Intervention Name(s)
Cyclophosphamide, Vincristine, Doxorubicin, Prednisone
Intervention Description
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.
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD)
Description
To determine the MTD for belinostat when combined with CHOP regimen and establish the Phase 3 recommended belinostat dose.
Time Frame
up to 5 days
Secondary Outcome Measure Information:
Title
Safety and tolerance
Description
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.
Time Frame
up to 5 days
Title
Overall Response Rate
Description
Overall response rate (ORR) after 6 cycles of BelCHOP regimen
Time Frame
126 days
Title
Effectiveness of study drug
Description
Pharmacokinetics of belinostat when co-administered with CHOP regimen. The concentration of Belinostat to assess the effectiveness.
Time Frame
126 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mi Rim Choi, MD
Organizational Affiliation
Spectrum Pharmaceuticals, Inc
Official's Role
Study Director
Facility Information:
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06511
Country
United States
Facility Name
Northeast Georgia Cancer Care, LLC
City
Athens
State/Province
Georgia
ZIP/Postal Code
30607
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
John Theurer Cancer Center at Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Hematology - Oncology Associates of Northern NJ P.A
City
Morristown
State/Province
New Jersey
ZIP/Postal Code
07962
Country
United States
Facility Name
Columbia University Medical Center/Center for Lymphiod Malignancies
City
New York
State/Province
New York
ZIP/Postal Code
10019
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
33602316
Citation
Johnston PB, Cashen AF, Nikolinakos PG, Beaven AW, Barta SK, Bhat G, Hasal SJ, De Vos S, Oki Y, Deng C, Foss FM. Belinostat in combination with standard cyclophosphamide, doxorubicin, vincristine and prednisone as first-line treatment for patients with newly diagnosed peripheral T-cell lymphoma. Exp Hematol Oncol. 2021 Feb 18;10(1):15. doi: 10.1186/s40164-021-00203-8.
Results Reference
derived
Learn more about this trial
Phase 1 Dose Finding Study of Belinostat for Treatment of Patients With Peripheral T-cell Lymphoma (PTCL)
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