Study: Treatment of Relapsed Lymphoid Malignancies With an Anti-Angiogenic Approach
1.1 To determine the efficacy of a combination treatment of VP-16, chlorambucil, dexamethasone, and vincristine in patients with relapsed/refractory hematological malignancies.
1.2 To determine the toxicity profile of the above regimen in this patient population.
1.3 Evaluate the effect of low dose administration of chemotherapy on angiogenesis, and correlate this with tumor responses.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study: Treatment of Relapsed Lymphoid Malignancies With an Anti-angiogenic Approach|
- Overall Response Rate (ORR), the Sum of Complete and Partial Responses [ Time Frame: Up to 6 months after first on-study treatment ] [ Designated as safety issue: Yes ]
Solid tumor response is per Response Evaluation Criteria in Solid Tumors (RECIST) (ver 1.0).
For CLL: complete remission (CR) requires the following for>=2 months 1) no symptoms attributable to CLL, 2) normal physical examination, 3) absolute lymphocyte count<4,000/µL, 4) ANC>1,500/µL, 5) platelets>100,000/µL, 6) hemoglobin>11 g/dL, 7) bone marrow lymphocytosis<30%, 8) no nodules in bone marrow. Partial response (PR) requires the following for >=2 months 1) decrease in previously enlarged nodes, spleen, and liver by >=50%, 2) ANC>=1,500/µL or platelets>=100,000/µL, 3) hemoglobin>=11 g/dL, 4) 50% improvement over pre-therapy reductions in hemoglobin and/or platelets.
For MM, CR is no monoclonal protein (M-protein) in blood and urine and <5% plasma cells in bone marrow on >=2 determinations >=6 wk apart & stable bone disease & calcium levels. PR is>50% and >90% decreases in serum & urine M-protein, respectively, on >=2 occasions for >=6 wk, stable bone disease & calcium.
- Toxicity [ Time Frame: End of 2 cycles (cycle = 28 days) ] [ Designated as safety issue: Yes ]
|Study Start Date:||October 2004|
|Study Completion Date:||May 2014|
|Primary Completion Date:||November 2008 (Final data collection date for primary outcome measure)|
Experimental: Arm 1 Combination Treatment
Treatment with combination therapy as follows:
VP-16 at 50 mg/day, orally for 14 days every 28 days; Chlorambucil at 0.1 mg/kg/day orally for 14 days every 28 days; Vincristine at 2 mg intravenously every 14 days; Dexamethasone at 200 mg intravenously every 24 days; Rituxan (rituximab) at 375 mg/m2 intravenously every 14 day; Levofloxacin at 500 mg orally daily; Diflucan at 200 mg orally daily
At least 2 courses, but no more than 8 courses total, will be administered to each patient
Vincristine should be administered intravenously through a freely-running IV.
Other Name: OncovinDrug: VP-16
The VP-16 is optional for the first cycle if the patient has delays in obtaining the drug.
Other Names:Drug: Rituximab
The total amount of rituximab needed for a patient's entire infusions (one course) will be determined at study entry. A single dose of 375 mg/m2 will be based upon the patient's actual body surface area calculated during the baseline evaluation. The dose level of rituximab will not be adjusted.
Patients will only receive rituximab if their tumors are CD20 positive CLL or NHL.
Rituximab will only be administered to patients if they have previously had less than 8 doses. If a patient is treated with rituxan they should have at least 4 doses
Other Name: RituxanDrug: Dexamethasone
Dexamethasone will be administered at 200mg q 14 days. Dexamethasone should be administered over a 1 hour infusion.
Other Name: decadronDrug: Levofloxacin
Levofloxacin will be administered at 500 mg PO qd.
The purpose of the study is to see how effective the combination of chemotherapy drugs VP-16, chlorambucil, dexamethasone, and vincristine is for patients who have blood cancers that have returned or not responded to prior treatment. Some patients may also receive a medication called rituximab if their doctor thinks it is appropriate. This drug combination will be given to study participants in a low dose continuous basis. The study will also collect information about the side effects of the above drug combination on patients with these types of cancers. Previous studies on patients with non-Hodgkin's lymphoma indicate that some patients treated with this drug combination achieved a high response. The aim of this study is to test this drug combination in a controlled setting.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00250718
|United States, New Mexico|
|University of New Mexico Cancer Center|
|Albuquerque, New Mexico, United States, 87131|
|Principal Investigator:||Dulcinea Quintana, MD||UNM Cancer Center|
|Study Chair:||Robert Hromas, MD||University of Florida|