Non-Hodgkin's Lymphoma
Conditions
Brief summary
The current standard treatment for non-Hodgkin's lymphoma involves drugs called cyclophosphamide, doxorubicin, vincristine, prednisone and rituxan in a regimen called R-CHOP. Using R-CHOP therapy, complete disappearance of disease is expected in over 50% of people. One of the active drugs in the R-CHOP regimen, doxorubicin, has previously been reformulated and been placed in a fatty bubble called a liposome. The reason for placing the drug in the liposome is that there is evidence that the liposome is better taken up by tumors. This liposomally encapsulated form of doxorubicin called Doxil has shown similar or better anti-tumor against certain tumors with reduced side effects. Doxil is FDA approved for ovarian cancer. However its use in non-Hodgkin's lymphoma is still investigational. By substituting Doxil for doxorubicin in the R-CHOP regimen, it is hoped this treatment will be better at shrinking tumors and with reduced side effects. The purpose of this study is to see how well the combination of Doxil, rituximab, cyclophosphamide, vincristine and prednisone (DR-COP) are in shrinking tumors in patients with non-Hodgkin's lymphoma.
Interventions
DRUGDoxorubicin, Rituxan, Cyclophosphamide, Vincristine and Prednisone
Cycle 1 Doxil 40 mg/m2 iv day 1 over a minimum of 60 min. Cyclophosphamide 750 mg/m2 iv day 1 over a minimum of 60 min. Vincristine 1.4 mg/m2 iv bolus day 1 (2.0 mg maximum). Prednisone 100 mg po days 1-5. Cycle 2 until study completion Doxil 40 mg/m2 iv day 1 Rituxan 375 mg/m2 iv day 1 Cyclophosphamide 750 mg/m2 iv day 1 Vincristine 1.4 mg/m2 iv bolus day 1 (2.0 mg maximum) Prednisone 100 mg po days 1-5 * 1 cycle = 21 days. * Continue treatment until 2 cycles beyond documentation of CR for a maximum of 8 cycles.
Sponsors
Ortho Biotech, Inc.
University of Southern California
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
* Pathologic diagnosis of Non-Hodgkin's lymphoma of B-cell origin: follicular large cell, diffuse large cell (including all B-cell variants), Burkitt or Burkitt-like lymphoma * All stages of disease * Measurable or evaluable tumor parameter(s) * Age greater than 17 years old * Karnofsky performance status greater or equal to 50% * AGC greater or equal to 1.0; platelets greater or equal to 75,000(unless abnormal because of lymphoma) * Bilirubin less or equal to 2.0; SGOT less or equal to 3 times upper limit of normal (unless abnormal because of lymphoma) * Creatinine less or equal to 2.0 or creatinine clearance greater or equal to 60 ml/min (unless abnormal because of lymphoma) * LVEF greater or equal to 45% * Concurrent RT with or without steroids for emergency conditions secondary to lymphoma (i.e., CNS tumor, cord compression)are permitted * Men and women of childbearing potential must agree to use adequate birth control for the duration of the therapy and for 3 months after completion of therapy * Signed informed consent
Exclusion criteria
* Prior systemic cytotoxic therapy or RT for lymphoma * Second active tumor, other than non-melanomatous skin ca and in-situ cervical cancer * HIV seropositive * Primary CNS lymphoma * Pregnant or nursing women * Unable to comply with the requirements of the protocol, or unable to provide adequate informed consent, in the opinion of the PI
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Complete Response to the Combination Chemotherapy | At completion of cycle 4, 6, and 8 | Initial disease response tests will be performed after cycle 4 on all patients. Subsequent assessments after cycles 6 and/or 8 will depend on response. If after 4 cycles of therapy complete response or partial response has been documented, therapy will continue. If stable or progressive disease has been documented, the patient will be withdrawn from the study. Response to the study treatment will be determined according to the criteria proposed in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al (23). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Serious Adverse Events as a Measure of Safety and Tolerability | At end of every cycle | Summary of grade 3 or higher toxicities (per Common Toxicity Criteria version 2.0) which generally is described as severe adverse reaction or symptom. |
Countries
United States
Participant flow
Recruitment details
The study began recruiting in January 2003 and ended in December 2007. All subjects were seen and treated either at USC Norris Comprehensive Cancer Center or at LAC+USC Medical Center.
Pre-assignment details
There were no pre-assignment criteria. All subjects were given the same treatment.
Participants by arm
| Arm | Count |
|---|---|
| DR-COP On cycle 1 patients receive Doxil 40 mg/m2 iv day 1 over a minimum of 60 min., Cyclophosphamide 750 mg/m2 iv day 1 over a minimum of 60 min., Vincristine 1.4 mg/m2 iv bolus day 1 (2.0 mg maximum) and Prednisone 100 mg po days 1-5.
On cycle 2 until study completion patients receive Doxil 40 mg/m2 iv day 1, Rituxan 375 mg/m2 iv day 1, Cyclophosphamide 750 mg/m2 iv day 1, Vincristine 1.4 mg/m2 iv bolus day 1 (2.0 mg maximum) and Prednisone 100 mg po days 1-5
* 1 cycle = 21 days.
* Continue treatment until 2 cycles beyond documentation of CR for a maximum of 8 cycles.
Doxorubicin, Rituxan, Cyclophosphamide, Vincristine and Prednisone: Cycle 1 Doxil 40 mg/m2 iv day 1 over a minimum of 60 min.
Cyclophosphamide 750 mg/m2 iv day 1 over a minimum of 60 min.
Vincristine 1.4 mg/m2 iv bolus day 1 (2.0 mg maximum).
Prednisone 100 mg po days 1-5.
Cycle 2 until study completion
Doxil 40 mg/m2 iv day 1
Rituxan 375 mg/m2 iv day 1
Cyclophosphamide 750 mg/m2 iv day 1 | 68 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 9 |
| Overall Study | Death | 3 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | DR-COP |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 60 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 48 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 48 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Region of Enrollment United States | 68 participants |
| Sex: Female, Male Female | 39 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 68 |
| other Total, other adverse events | 27 / 68 |
| serious Total, serious adverse events | 35 / 68 |
Outcome results
Primary
Percentage of Patients With Complete Response to the Combination Chemotherapy
Initial disease response tests will be performed after cycle 4 on all patients. Subsequent assessments after cycles 6 and/or 8 will depend on response. If after 4 cycles of therapy complete response or partial response has been documented, therapy will continue. If stable or progressive disease has been documented, the patient will be withdrawn from the study. Response to the study treatment will be determined according to the criteria proposed in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al (23).
Time frame: At completion of cycle 4, 6, and 8
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DR-COP | Percentage of Patients With Complete Response to the Combination Chemotherapy | Complete Response | 75.0 Percentage of participants |
| DR-COP | Percentage of Patients With Complete Response to the Combination Chemotherapy | Partial Response | 23.0 Percentage of participants |
Secondary
Number of Patients With Serious Adverse Events as a Measure of Safety and Tolerability
Summary of grade 3 or higher toxicities (per Common Toxicity Criteria version 2.0) which generally is described as severe adverse reaction or symptom.
Time frame: At end of every cycle
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DR-COP | Number of Patients With Serious Adverse Events as a Measure of Safety and Tolerability | 35 Participants |