Previously Untreated Peripheral T-cell Lymphoma
Conditions
Keywords
Peripheral T-cell Lymphoma, Azacitidine, Lymphoma
Brief summary
This is a phase II, multi-center study to determine the efficacy and safety of first-line CC-486 plus CHOP in patients with PTCL who have received no prior systemic therapy. The study has a sample size of 20, and follows two-stage minimax design for primary efficacy analysis.
Detailed description
Study Summary: This is a phase II, multi-center study to determine the efficacy and safety of first-line CC-486 plus CHOP in patients with Peripheral T-cell Lymphoma (PTCL) who have received no prior systemic therapy. The main objective is to determine the complete response rate (CR) of CC486-CHOP in PTCL. CR rate after cycle 6 will be used for the purpose of interim efficacy analysis. * The study includes 6 cycles (\ 18 weeks) of treatment and 2 years of follow-up. The projected end date is 12/31/2022. Patients achieving complete remission will be evaluated every 6 months for 2 years or until disease progression. Patients who have disease progression will be contacted every 6 months to assess for survival status. * Standard dose CHOP will be provided on day 1 of each cycle and repeat every 3 weeks for a total of 6 cycles. * CC486 at 300 mg daily will be administered orally from day -6 to day 0 for cycle 1 priming, and on days 8-21 following cycles 1-5. * Patients in CR/PR following 6 cycles of treatment have the option to proceed to consolidative autologous stem cell transplant. * Will continue on treatment as long as they are responding to therapy and not experiencing unacceptable side effects.
Interventions
DRUGCC-486 Administration
CC-486 at 300 mg once daily is to be administered Cycle 1, Day -6 to 0 and Cycles 1 to 5, Day 8 to 21. Antiemetic prophylaxis is recommended before dosing. All efforts should be made to administer CC-486 on all scheduled days of the Cycle 1 priming dosing (7 days, Cycle 1 Day -6 to Cycle 1 Day 0) and the Cycle 1-5 dosing (14 days, Day 8-21). A dose missed earlier in a day can be administered later that day as long as it is taken at least 8 hours before the next scheduled dose. Any missed dose should not be taken beyond the last scheduled day of CC-486 administration for the cycle, but should be returned by the subject for CC 486 accountability. If vomiting occurs after a dose of CC-486 is administrated, that dose should not be made up later that day.
DRUGCHOP Administration
CHOP is to be administered on Days 1 to 5 of Cycles 1-6. Chemotherapy can be administer within +72h or -24h of Day 1 of each scheduled Cycle. Preparation and infusion rate are according to the package insert and local practice. The doses to be used are: Cyclophosphamide: 750 mg/m2 IV on day 1 Doxorubicin: 50 mg/m2 IV on day 1 Vincristine: 1.4 mg/m2 IV (not to exceed 2.0 mg total) on day 1 Prednisone: 100 mg PO days 1-5
Sponsors
Celgene Corporation
Weill Medical College of Cornell University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a phase II, multi-center study to determine the efficacy and safety of first-line CC-486 plus CHOP in patients with PTCL who have received no prior systemic therapy. The study has a sample size of 20, and follows two-stage minimax design for primary efficacy analysis.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
\- Histologically confirmed diagnosis of PTCL of the following subtypes: Nodal T-cell lymphoma with T-follicular helper (TFH) phenotype (tumor cells must express 2 or 3 TFH-related antigens, including PD1, CD10, BCL6, CXCL13, ICOS, SAP and CCR5)\* Angioimmunoblastic T-cell lymphoma Follicular T-cell lymphoma PTCL/NOS, T-follicular helper (TFH) variant PTCL-NOS Anaplastic large cell lymphoma, ALK negative Anaplastic large cell lymphoma, ALK positive with IPI \> 2 Adult T-cell leukemia / lymphoma * No prior systemic therapy for lymphoma * Measurable disease defined by a tumor mass ≥ 1.5 cm in one dimension and measurable in two dimensions * ECOG performance status ≤ 2
Exclusion criteria
* Known central nervous system (CNS) involvement by lymphoma * Active viral infection with HIV or hepatitis type B or C (seropositive HBV patients are eligible if they are negative for HBV DNA by PCR and receive concomitant antiviral therapy). * Prior history of malignancies other than PTCL unless the patient has been disease free for ≥ 5 years from the signing of the ICF.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate | After Cycle 6 at 18 weeks | Complete response rate (CR) of CC486-CHOP in PTCL by Lugano Criteria for target lesions, and the Deauville Criteria (5 point scale) assessed by PET or CT; CR (complete metabolic or radiologic response) defined as Deauville score of 1, 2 or 3 by PET or regression of all target lesions to \< 1.5cm in longest diameter by CT. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kaplan-Meier Overall Survival | 2 years | Overall Survival (OS) assessed by Kaplan-Meier survival analysis. The Kaplan-Meier overall survival estimate at 2 years (with 95% confidence interval) is reported. OS defined as the time from first treatment day until death (or until last follow-up if alive). |
| Kaplan-Meier Progression-Free Survival | 2 years | Progression-free survival (PFS) assessed by Kaplan-Meier survival analysis. The Kaplan-Meier progression-free survival estimate at 2 years (with 95% confidence interval) is reported. PFS defined as the time from first treatment day until objective or symptomatic progression or death (or date of last follow-up if no progression/death). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CC486 +CHOP CC486 +CHOP
CC-486 Administration: CC-486 at 300 mg once daily is to be administered Cycle 1, Day -6 to 0 and Cycles 1 to 5, Day 8 to 21. Antiemetic prophylaxis is recommended before dosing. All efforts should be made to administer CC-486 on all scheduled days of the Cycle 1 priming dosing (7 days, Cycle 1 Day -6 to Cycle 1 Day 0) and the Cycle 1-5 dosing (14 days, Day 8-21). A dose missed earlier in a day can be administered later that day as long as it is taken at least 8 hours before the next scheduled dose. Any missed dose should not be taken beyond the last scheduled day of CC-486 administration for the cycle, but should be returned by the subject for CC 486 accountability. If vomiting occurs after a dose of CC-486 is administrated, that dose should not be made up later that day.
CHOP Administration: CHOP is to be administered on Days 1 to 5 of Cycles 1-6. Chemotherapy can be administer within +72h or -24h of Day 1 of each scheduled Cycle. Preparation and infusion rate are according to the package insert and local practice. The doses to be used are:
Cyclophosphamide: 750 mg/m2 IV on day 1 Doxorubicin: 50 mg/m2 IV on day 1 Vincristine: 1.4 mg/m2 IV (not to exceed 2.0 mg total) on day 1 Prednisone: 100 mg PO days 1-5 | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Treatment Phase | Adverse Event | 1 |
| Treatment Phase | PD | 1 |
| Treatment Phase | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | CC486 +CHOP |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 12 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Region of Enrollment United States | 21 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 21 |
| other Total, other adverse events | 21 / 21 |
| serious Total, serious adverse events | 6 / 21 |
Outcome results
Primary
Complete Response Rate
Complete response rate (CR) of CC486-CHOP in PTCL by Lugano Criteria for target lesions, and the Deauville Criteria (5 point scale) assessed by PET or CT; CR (complete metabolic or radiologic response) defined as Deauville score of 1, 2 or 3 by PET or regression of all target lesions to \< 1.5cm in longest diameter by CT.
Time frame: After Cycle 6 at 18 weeks
Population: 3 of 21 participants did not complete treatment as outlined in the Participant Flow section; these subject were unevaluable and not included in analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CC486 +CHOP | Complete Response Rate | 75 percentage of participants |
95% CI: [46.5, 90.3]
Secondary
Kaplan-Meier Overall Survival
Overall Survival (OS) assessed by Kaplan-Meier survival analysis. The Kaplan-Meier overall survival estimate at 2 years (with 95% confidence interval) is reported. OS defined as the time from first treatment day until death (or until last follow-up if alive).
Time frame: 2 years
Population: 1 patient had missing overall survival information.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CC486 +CHOP | Kaplan-Meier Overall Survival | 68.0 percentage of participants |
Secondary
Kaplan-Meier Progression-Free Survival
Progression-free survival (PFS) assessed by Kaplan-Meier survival analysis. The Kaplan-Meier progression-free survival estimate at 2 years (with 95% confidence interval) is reported. PFS defined as the time from first treatment day until objective or symptomatic progression or death (or date of last follow-up if no progression/death).
Time frame: 2 years
Population: 1 participant had missing progression-free survival information.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CC486 +CHOP | Kaplan-Meier Progression-Free Survival | 65.8 percentage of participants |