Peripheral T-cell Lymphoma
Conditions
Keywords
PTCL, Maximum Tolerated Dose, Belinostat
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.
Interventions
DRUGBelinostat
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
DRUGCHOP
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.
Sponsors
Acrotech Biopharma Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Overall Response Rate | 126 days | Overall response rate (ORR) after 6 cycles of BelCHOP regimen |
| Effectiveness of study drug | 126 days | Pharmacokinetics of belinostat when co-administered with CHOP regimen. The concentration of Belinostat to assess the effectiveness. |
Countries
United States
Outcome results
None listed