- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00083551
UARK 98-026 TT II: Multiple Myeloma Evaluating Anti-Angiogenesis With Thalidomide and Post-Transplant Consolidation Chemotherapy
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
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
Arkansas
-
Little Rock, Arkansas, United States, 72205
- University of Arkansas for Medical Sciences/MIRT
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Thalidomide
Thalidomide 400 qod during induction.100
mg qd between transplants, post transplant pat.
200 mg qd.
During year one of maintenance therapy pt will take 100mg of Thal qod and 50 mg of thal qod during second year of maintenance
|
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:
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:
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:
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:
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.
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
Other Names:
|
Active Comparator: No Thalidomide
During induction, consolidation, and maintenance steps patient receives no thalidamide
|
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:
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:
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:
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.
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
Other Names:
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:
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:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival
Time Frame: 6 Years
|
Overall Survival at six years after initiating protocol therapy
|
6 Years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Bart Barlogie, M.D., Ph.D., UAMS
Publications and helpful links
General Publications
- Vatsveen TK, Sponaas AM, Tian E, Zhang Q, Misund K, Sundan A, Borset M, Waage A, Brede G. Erythropoietin (EPO)-receptor signaling induces cell death of primary myeloma cells in vitro. J Hematol Oncol. 2016 Aug 31;9(1):75. doi: 10.1186/s13045-016-0306-x.
- Usmani SZ, Heuck C, Mitchell A, Szymonifka J, Nair B, Hoering A, Alsayed Y, Waheed S, Haider S, Restrepo A, Van Rhee F, Crowley J, Barlogie B. Extramedullary disease portends poor prognosis in multiple myeloma and is over-represented in high-risk disease even in the era of novel agents. Haematologica. 2012 Nov;97(11):1761-7. doi: 10.3324/haematol.2012.065698. Epub 2012 Jun 11.
- Barlogie B, Tricot G, Anaissie E, Shaughnessy J, Rasmussen E, van Rhee F, Fassas A, Zangari M, Hollmig K, Pineda-Roman M, Lee C, Talamo G, Thertulien R, Kiwan E, Krishna S, Fox M, Crowley J. Thalidomide and hematopoietic-cell transplantation for multiple myeloma. N Engl J Med. 2006 Mar 9;354(10):1021-30. doi: 10.1056/NEJMoa053583.
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Autonomic Agents
- Peripheral Nervous System Agents
- Antiviral Agents
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Anti-Bacterial Agents
- Leprostatic Agents
- Antibiotics, Antineoplastic
- Dexamethasone
- Interferons
- Interferon-alpha
- Cyclophosphamide
- Etoposide
- Cisplatin
- Thalidomide
- Interferon alpha-2
- Melphalan
- Doxorubicin
- Cytarabine
- Vincristine
- Carmustine
Other Study ID Numbers
- 5226
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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