This study has been designed to evaluate whether "anti-angiogenesis" therapy with thalidomide and whether additional chemotherapy after transplant will be beneficial. Another objective is to find out what kinds of side effects occur with this combination of treatment and how often they occur.
Treatment will be given in 4 phases or steps: Induction, Transplant 1 and 2, Consolidation, and maintenance. Induction is designed to induce (or bring about) myeloma into remission. Each patient enrolled on this study will be randomly assigned to receive the above treatment alone or in combination with a drug called thalidomide. Some patients may be eligible to receive the transplant as an outpatient, based on general health and other factors.After recovery from the transplant phase of the study (approximately 6 weeks), patients originally assigned to thalidomide will resume taking it and will continue taking it throughout the rest of the study treatment. All patients will receive post-transplant consolidation treatment, which in earlier studies has been found to be helpful in maintaining patients response after transplant. Therefore, all patients will receive a combination of drugs called "D PACE" which consists of Dexamethasone, Cis-Platinum, Adriamycin, Cyclophosphamide, and Etoposide. If you are also taking thalidomide, you will continue taking it throughout, and the treatment is called "DT PACE" to include the thalidomide. No sooner than 4 weeks, and no later than 12 weeks after consolidation and if your myeloma remains in remission after consolidation therapy is complete, you will begin the last phase of the study, which is maintenance. Maintenance is designed to keep your myeloma in remission long-term.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
668
All patients will be randomly assigned to receive thalidomide 400 mg as an oral, once daily dose throughout induction and 100mg between transplants after platelets are greater than 50,000μl and 200 mg post transplant consolidation, and a reduced dose of 100 mg on alternating days during the first year of maintenance and 50 mg qod thereafter versus no thalidomide. Thalidomide will be held during conditioning, transplant procedure, and recovery following transplant. It may be resumed once plateletrecovery is complete after each transplant
Cytarabine (Ara-C) 400 mg/m2 in 250 ml D5W over one hour daily for four days (on days -5, -4, -3, -2). Start infusion 30 minutes after completion of BCNU on day -5.
Carmustine (BCNU) 300 mg/m2 in 1 liter of D5W in glass bottle (protect from light) to infuse over 2 hours on day -5. Check blood pressure every 15 minutes during infusion and 30 minutes after completion
University of Arkansas for Medical Sciences/MIRT
Little Rock, Arkansas, United States
Overall Survival
Overall Survival at six years after initiating protocol therapy
Time frame: 6 Years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Cisplatin\* 15 mg/m2/day Continuous infusion 1-4 (DCEP CYCLE 2) Cisplatin\* 7.5 mg/m2 Continuous infusion 1-4 (DPACE cycle) \*Cisplatin doses will be modified for renal insufficiency as follows: Cisplatin dose Creatinine 15 mg/m2 (full dose) \< 1.5 mg/dl 10 mg/m2 1.6 - 2.0 mg/dl 7.5 mg/m2 2.1 - 3.0 mg/dl 0 mg (hold Cisplatin) \> 3.0 mg/dl
Cycle 2 - DCEP Cyclophosphamide 400 mg/m2/day Continuous infusion 1-4 Cycle 3 - CAD and PBSC Collection #1 Cyclophosphamide 750 mg/m2/day Continuous infusion 1-4 Cycle 4 - DCEP Cyclophosphamide 400 mg/m2/day Continuous infusion 1-4 Cytoxan/VP-16 and PBSC Collection-Cyclophosphamide 2 grams/m2 (Total dose 4 gm/m2) IV by CI 1 and 2 Post-Transplant Consolidation-Cyclophosphamide 300 mg/m2 Continuous infusion 1-4
Induction cycle 1 VAD Dexamethasone 40 mg/day PO 1-4, 9-12, 17-20 Cycle 2 - DCEP Dexamethasone 40 mg/day PO 1-4 Cycle 3 - CAD and PBSC Collection #1 Dexamethasone 40 mg/day PO 1-4 Cycle 4 - DCEP and PBSC Collection #2 Dexamethasone 40 mg/day PO 1-4 Post-Transplant Consolidation Dexamethasone 40 mg PO 1-4 Dexamethasone Consolidation Patients that do not achieve adequate platelet recovery (defined as \< 80,000/μl) will receive consolidation with Dexamethasone 40 mg x 4 days every 28 days for 1 year Maintenance year one Dexamethasone 40 mg PO q 3 months, day 1-4, 9-12, 17-20
Doxorubicin may be further diluted in 5% dextrose or sodium chloride injection and should be administered slowly into tubing of a freely flowing intravenous infusion with great care taken to avoid extravasation.
Etoposide (VP16) 200 mg/m2 in 500 ml D5W over one hour daily for four days (on days -5, -4, -3, -2). Start infusion 30 minutes after completion of BCNU on day -5. Start infusion at completion of cytarabine on following three days
G-CSF will be administered at a dose of 10mcg/kg or GM-CSF at a dose of 10 mcg/kg. G-CSF or GM-CSF will begin one day after completion of chemotherapy and continued during repeated apheresis and discontinued upon completion of apheresis.
GM-CSF at a dose of 10 μg/kg SC, divided in 2 doses each day, will begin one day after completion of chemotherapy and continued during repeated apheresis and discontinued upon completion of apheresis.
AGENT DOSE ROUTE DAYS Intron-A 3 million units/m2 SQ TIW Thalidomide (for those randomized at initial registration) 50 mg QOD PO Every other day (qod
Etoposide (VP16) 200 mg/m2 in 500 ml D5W over one hour daily for four days (on days -5, -4, -3, -2). Start infusion 30 minutes after completion of BCNU on day -5. Start infusion at completion of cytarabine on following three days
Formulation: 1 mg/1 ml, 2 mg/2 ml, and 5 mg/ 5 ml vials. Vincristine should be administered intravenously through a freely-running IV. If it extravasates, it produces a severe local reaction with skin slough. FATAL IF GIVEN INTRATHECALLY, FOR INTRAVENOUS USE ONLY.