Diffuse Large-Cell Lymphoma
Conditions
Keywords
lymphoma, NHL, large cell, phase II, CHOP R, CPOP R, non Hodgkins
Brief summary
The purpose of this study is to compare the standard CHOP-R regimen of Cyclophosphamide, Doxorubicin, Vincristine, Prednisone, and Rituximab to CPOP-R (same regimen, but substituting Doxorubicin with Pixantrone). The objective is to show that CPOP-R is not inferior to CHOP-R.
Detailed description
In preclinical studies, pixantrone has shown significantly less cardiotoxicity than other anthracyclines or anthracenediones. In addition, patients with relapsed disease, who have received prior maximum doses of anthracyclines, have tolerated high doses of pixantrone with minimal added cardiotoxicity. Pixantrone is currently being studied in a Phase III study in 3rd line aggressive NHL.
Interventions
DRUGCPOP-R
Cyclophosphamide 750 mg/m2, pixantrone 150 mg/m2, vincristine 1.4 mg/m2, rituximab 375 mg.m2 on Day 1 of a 21 day cycle, for 8 cycles Prednisone 100 mg/day on Day 1-5 of a 21 day cycle for 8 cycles
DRUGCHOP-R
Cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, rituximab 375 mg.m2 on Day 1 of a 21 day cycle, for 8 cycles Prednisone 100 mg/day on Day 1-5 of a 21 day cycle for 8 cycles
Sponsors
CTI BioPharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Previously untreated and histologically confirmed diffuse large B-cell lymphoma according to REAL/WHO classification. 2. Stage II, III or IV disease 3. CD20+ 4. Age ≥ 18 years 5. ECOG performance status ≤ 2 6. At least one objectively bidimensionally measurable lesion as demonstrated by CT, spiral CT, or MRI that can be followed for response as target lesion. Patients with the following sites of disease are NOT eligible: * Patients with only skin lesions or only palpable lymph nodes. * Patients with spleen or bone marrow as only site of disease. 7. Life expectancy ≥ 3 months 8. Serum bilirubin ≤ 1.5 x the institution's upper limit normal (ULN) and creatinine ≤ 2.0 ULN and AST or ALT ≤ 2.0 x the institution's ULN. If hepatic involvement by lymphoma is present, AST or ALT may be ≤ 5.0 x the institution's ULN. 9. LVEF ≥ 50% determined by MUGA scan. 10. Ability to comply with the visit schedule and assessments required by the protocol. 11. Signed approved informed consent, with understanding of study procedures.
Exclusion criteria
1. Any prior chemotherapy (except intrathecal chemotherapy at diagnosis and pretreatment corticosteroid therapy) or radiotherapy: Patients may receive corticosteroid pretreatment therapy for up to 7 days after randomization, pending Investigator's decision to reduce tumor burden. 2. Histological diagnosis of T-cell lymphoma or any B-cell lymphoma other than diffuse large B-cell. 3. History of indolent lymphoma 4. Active CNS involvement based on clinical evaluation . 5. HIV-related lymphoma. 6. Major thoracic and/or abdominal surgery within the 4 weeks before randomization from which the patient has not fully recovered except for diagnosis of NHL. Patients who have had minor surgery may be enrolled after a ≥ 1 week recovery period except for diagnosis of NHL. 7. Clinically significant cardiovascular abnormalities 8. Serious (NCI CTCAE grade 3-4) intercurrent infection at randomization or deep seated or systemic mycotic infections. 9. Clinical symptoms suggesting unresolved HIV, HBV or HCV infection. Patients with seropositivity presumed to be due to prior vaccination against Hepatitis B virus or resolved infection will not be excluded. 10. Active or history of another malignancy except cured basal cell carcinoma of skin or carcinoma in situ of uterine cervix. Patients who have been in remission from another previous malignancy for \>5 years will be considered eligible. 11. Known hypersensitivity to the excipients or the study drugs that the patient will receive. 12. Any contraindications to the study drugs as described in the Summary of Product Characteristics or package inserts. 13. Neurological contraindication to vincristine (e.g. peripheral neuropathy). 14\. Any condition which, in the judgment of the Investigator, would place the subject at undue risk, interfere with the results of the study, or make the subject otherwise unsuitable. 15. General status that, in the opinion of the Investigator does not permit the administration of eight courses of CHOP-R/CPOP-R. 16. Treatment with any other investigational study drug within 30 days before randomization. Patient must have recovered from all side effects of other investigational therapy. 17. Potentially fertile men and women and their sexual partners not willing to use adequate contraception as defined by the Investigator during the study and for 6 months after the last day of study drug administration. 18\. Any circumstance at the time of study entry that would preclude completion of the study or the required follow-up.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Response Rate | Subjects followed for 5 years post treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | The interval between the date of randomization and death due to any cause (up to 100 weeks) | Overall Survival time frame is from the interval between the date of randomization and death due to any cause and measures the total number of deaths. |
| Median Progression Free Survival (PFS) | From the date of randomization to the first documented disease progression or death (up to 100 weeks) | The interval between the date of randomization and the event of disease progression or relapse, institution of a new anticancer treatment or death. |
| Overall Objective Response Rate | Subjects followed for 5 years post treatment | — |
| Time to Treatment Failure | Subjects followed for 5 years post treatment | — |
Countries
Canada, France, Germany, Italy, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CPOP-R CPOP-R: Cyclophosphamide 750 mg/m2, pixantrone 150 mg/m2, vincristine 1.4 mg/m2, rituximab 375 mg.m2 on Day 1 of a 21 day cycle, for 8 cycles Prednisone 100 mg/day on Day 1-5 of a 21 day cycle for 8 cycles | 61 |
| CHOP-R CHOP-R: Cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, rituximab 375 mg.m2 on Day 1 of a 21 day cycle, for 8 cycles Prednisone 100 mg/day on Day 1-5 of a 21 day cycle for 8 cycles | 63 |
| Total | 124 |
Baseline characteristics
| Characteristic | CHOP-R | CPOP-R | Total |
|---|---|---|---|
| Age, Customized ≤ 65 Years | 29 Participants | 26 Participants | 55 Participants |
| Age, Customized >65 Years | 34 Participants | 35 Participants | 69 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Caucasian | 58 Participants | 51 Participants | 109 Participants |
| Race/Ethnicity, Customized Hispanic | 2 Participants | 6 Participants | 8 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Female | 34 Participants | 29 Participants | 63 Participants |
| Sex: Female, Male Male | 29 Participants | 32 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 18 / 59 | 9 / 63 |
| other Total, other adverse events | 59 / 59 | 63 / 63 |
| serious Total, serious adverse events | 28 / 59 | 26 / 63 |
Outcome results
Primary
Response Rate
Time frame: Subjects followed for 5 years post treatment
Population: Intent to Treat Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CPOP-R | Response Rate | Complete Response | 24 Participants |
| CPOP-R | Response Rate | Complete Response Unconfirmed | 20 Participants |
| CPOP-R | Response Rate | Response Rate | 44 Participants |
| CHOP-R | Response Rate | Complete Response | 28 Participants |
| CHOP-R | Response Rate | Complete Response Unconfirmed | 22 Participants |
| CHOP-R | Response Rate | Response Rate | 50 Participants |
Secondary
Median Progression Free Survival (PFS)
The interval between the date of randomization and the event of disease progression or relapse, institution of a new anticancer treatment or death.
Time frame: From the date of randomization to the first documented disease progression or death (up to 100 weeks)
Population: Intent to Treat Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CPOP-R | Median Progression Free Survival (PFS) | NA months |
| CHOP-R | Median Progression Free Survival (PFS) | 17.3 months |
Secondary
Overall Objective Response Rate
Time frame: Subjects followed for 5 years post treatment
Population: Intent to Treat Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CPOP-R | Overall Objective Response Rate | 50 Participants |
| CHOP-R | Overall Objective Response Rate | 55 Participants |
Secondary
Overall Survival
Overall Survival time frame is from the interval between the date of randomization and death due to any cause and measures the total number of deaths.
Time frame: The interval between the date of randomization and death due to any cause (up to 100 weeks)
Population: Intent to Treat (ITT) Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CPOP-R | Overall Survival | 18 Participants |
| CHOP-R | Overall Survival | 9 Participants |
Secondary
Time to Treatment Failure
Time frame: Subjects followed for 5 years post treatment
Population: Intent to Treat Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CPOP-R | Time to Treatment Failure | 30.3 Months |
| CHOP-R | Time to Treatment Failure | 40.1 Months |