Doxorubicin (Doxil) Combined With Rituxan, Cyclophosphamide, Vincristine and Prednisone in Newly Diagnosed Aggressive Non-Hodgkin's Lymphomas

Study Overview
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Brief Summary
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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.

Official Title
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A Phase II Study Of Pegylated Liposomal Doxorubicin (Doxil) In Combination With Rituxan, Cyclophosphamide, Vincristine and Prednisone (DR-COP) In Newly Diagnosed Aggressive Non-Hodgkin's Lymphomas

Conditions
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Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: Doxorubicin, Rituxan, Cyclophosphamide, Vincristine and Prednisone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DR-COP<br>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. | Drug: Doxorubicin, Rituxan, Cyclophosphamide, Vincristine and Prednisone<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | At completion of cycle 4, 6, and 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | At end of every cycle |