TT II: Multiple Myeloma Evaluating Anti-Angiogenesis With Thalidomide and Post-Transplant Consolidation Chemotherapy
Overview[ - collapse ][ - ]
| Purpose | 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. |
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| Condition | Multiple Myeloma |
| Intervention | Drug: Thalidomide Drug: Ara-C Drug: BCNU Drug: Cisplatin Drug: Cytoxan Drug: Dexamethasone Drug: Doxorubicin Drug: Etoposide Drug: Filgrastim Drug: Recombinant GM-CSF Drug: Interferon-alpha-2b Drug: Melphalan Drug: Vincristine |
| Phase | Phase 3 |
| Sponsor | University of Arkansas |
| Responsible Party | University of Arkansas |
| ClinicalTrials.gov Identifier | NCT00083551 |
| First Received | May 25, 2004 |
| Last Updated | November 5, 2013 |
| Last verified | November 2013 |
Tracking Information[ + expand ][ + ]
| First Received Date | May 25, 2004 |
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| Last Updated Date | November 5, 2013 |
| Start Date | August 1998 |
| Estimated Primary Completion Date | December 2014 |
| Current Primary Outcome Measures | Determine the beneficial role of anti-angiogenesis therapy with thalidomide and to determine the role of dose consolidation during consolidation therapy following tandem autotransplants with melphalan 200 mg/m2. [Time Frame: Overall event free survival time] [Designated as safety issue: No] |
| Current Secondary Outcome Measures | 1.1 Evaluate whether the addition of thalidomide during remission induction and with consolidation chemotherapy after two transplants and during maintenance can improve event free survival from 40 to 50% after 5 years. [Time Frame: Overall event free survival time] [Designated as safety issue: No] |
Descriptive Information[ + expand ][ + ]
| Brief Title | TT II: Multiple Myeloma Evaluating Anti-Angiogenesis With Thalidomide and Post-Transplant Consolidation Chemotherapy |
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| Official Title | UARK 98-026, Total Therapy II - A Phase III Study for Newly Diagnosed Multiple Myeloma Evaluating Anti-Angiogenesis With Thalidomide and Post-Transplant Consolidation Chemotherapy |
| Brief Summary | 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. |
| Detailed Description | 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 |
| Study Phase | Phase 3 |
| Study Design | Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment |
| Condition | Multiple Myeloma |
| Intervention | Drug: Thalidomide 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 Other Names: ThalomidDrug: Ara-C 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. Other Names: CytarabineDrug: BCNU 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 Other Names: CarmustineDrug: Cisplatin 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 Other Names:
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 Other Names:
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 Other Names: TobradexDrug: Doxorubicin 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. Other Names:
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 Other Names:
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. Other Names:
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. Drug: Interferon-alpha-2b 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 Drug: Melphalan 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 Other Names: AlkeranDrug: Vincristine 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. Other Names:
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Recruitment Information[ + expand ][ + ]
| Recruitment Status | Active, not recruiting |
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| Estimated Enrollment | 673 |
| Estimated Completion Date | December 2014 |
| Estimated Primary Completion Date | December 2014 |
| Eligibility Criteria | Inclusion Criteria: - Patients must have newly diagnosed active multiple myeloma requiring treatment. Patients with a previous history of smoldering myeloma will be eligible if there is evidence of progressive disease requiring chemotherapy. - Protein criteria must be present in order to evaluate response.Non-secretory patients are eligible provided the patient has > or = 20% plasmacytosis or multiple (>3) focal plasmacytomas on MRI or diffuse hyperintense signal on STIR images in the absence of hematopoietic growth factors is seen. - All necessary baseline studies for determining stage, bloodwork, and bone marrow must be obtained within 35 days prior to registration. - Patients must have received no more than one cycle of prior chemotherapy including one month of Dexamethasone and Thalidomide for this disease. Patients may have received prior radiotherapy provided approval has been obtained by one of the study coordinators. - Patients must have a performance status of 0-2 based on SWOG criteria. Patients with a poor performance status (3-4), based solely on bone pain, will be eligible. - Patients with renal failure, even if on dialysis, are eligible if it is felt to be due to myeloma and if the duration of renal failure does not exceed two months - Patients must be 75 years of age or less at the time of registration - All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines. - If medically appropriate, patients with pathologic fractures, pneumonia at diagnosis or hyperviscosity with shortness of breath should have these conditions attended to prior to registration. Exclusion Criteria: - Patients must not have significant co-morbid medical conditions or uncontrolled life threatening infection - Patients must not have uncontrolled diabetes - Patients with recent (< or =6 months) myocardial infarction, unstable angina, difficult to control congestive heart failure, uncontrolled hypertension, or difficult to control cardiac arrythmias are ineligible. Ejection fraction by ECHO or MUGA should be within the institutional normal range and must be performed within 42 days prior to registration. - Patients must not have a history of chronic obstructive or chronic restrictive pulmonary disease. - No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for at least three years.Prior malignancy is acceptable provided there has been no evidence of disease within the three-year interval and there must be no prior treatment with cytotoxic drugs that could potentially be assigned on this treatment protocol. - Pregnant or nursing women may not participate. Women of child-bearing potential must have a negative pregnancy documented within one week of registration. Women/men of reproductive potential may not participate unless they have agreed to use two forms of effective contraceptive method. |
| Gender | Both |
| Ages | 18 Years |
| Accepts Healthy Volunteers | No |
| Contacts | Not Provided |
| Location Countries | United States |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT00083551 |
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| Other Study ID Numbers | UARK 98-026 |
| Has Data Monitoring Committee | Yes |
| Information Provided By | University of Arkansas |
| Study Sponsor | University of Arkansas |
| Collaborators | Celgene Corporation |
| Investigators | Principal Investigator: Bart Barlogie, M.D., Ph.D. UAMS |
| Verification Date | November 2013 |
Locations[ + expand ][ + ]
| University of Arkansas for Medical Sciences/MIRT | Little Rock, Arkansas, United States, 72205 |
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