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UARK 98-026 TT II: Multiple Myeloma Evaluating Anti-Angiogenesis With Thalidomide and Post-Transplant Consolidation Chemotherapy

Primary Purpose

Multiple Myeloma

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Thalidomide
Ara-C
BCNU
Cisplatin
Cytoxan
Dexamethasone
Doxorubicin
Etoposide
Filgrastim
Recombinant GM-CSF
Interferon-alpha-2b
Melphalan
Vincristine
Sponsored by
University of Arkansas
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple Myeloma, Cancer, Therapy, Thalidomide, DTPACE, Transplant, VAD, DCEP, CAD, Consolidation, Melphalan

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Arkansas for Medical Sciences/MIRT

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Thalidomide

No Thalidomide

Arm Description

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

During induction, consolidation, and maintenance steps patient receives no thalidamide

Outcomes

Primary Outcome Measures

Overall Survival
Overall Survival at six years after initiating protocol therapy

Secondary Outcome Measures

Full Information

First Posted
May 25, 2004
Last Updated
October 21, 2015
Sponsor
University of Arkansas
Collaborators
Celgene Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT00083551
Brief Title
UARK 98-026 TT II: Multiple Myeloma Evaluating Anti-Angiogenesis With Thalidomide and Post-Transplant Consolidation Chemotherapy
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2015
Overall Recruitment Status
Completed
Study Start Date
August 1998 (undefined)
Primary Completion Date
August 2014 (Actual)
Study Completion Date
August 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Arkansas
Collaborators
Celgene Corporation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Multiple Myeloma, Cancer, Therapy, Thalidomide, DTPACE, Transplant, VAD, DCEP, CAD, Consolidation, Melphalan

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
668 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Thalidomide
Arm Type
Active Comparator
Arm Description
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
Arm Title
No Thalidomide
Arm Type
Active Comparator
Arm Description
During induction, consolidation, and maintenance steps patient receives no thalidamide
Intervention Type
Drug
Intervention Name(s)
Thalidomide
Other Intervention Name(s)
Thalomid
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Ara-C
Other Intervention Name(s)
Cytarabine
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
BCNU
Other Intervention Name(s)
Carmustine
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
cisplatinum, cis-diamminedichloroplatinum, Platinol, Platinol-AQ
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Cytoxan
Other Intervention Name(s)
Cyclophosphamide, Endoxan, Neosar, Procytox, Revimmune, cytophosphane
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Other Intervention Name(s)
Tobradex
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Other Intervention Name(s)
Adriamycin, hydroxydaunorubicin
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Etoposide
Other Intervention Name(s)
Eposin, Etopophos, Vepesid, VP-16
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Filgrastim
Other Intervention Name(s)
Neupogen, Grafeel, Religrast, Nugraf, Shilgrast, Neukine, Emgrast
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Recombinant GM-CSF
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Interferon-alpha-2b
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Melphalan
Other Intervention Name(s)
Alkeran
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Vincristine
Other Intervention Name(s)
Oncovin, leurocristine
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall Survival
Description
Overall Survival at six years after initiating protocol therapy
Time Frame
6 Years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bart Barlogie, M.D., Ph.D.
Organizational Affiliation
UAMS
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Arkansas for Medical Sciences/MIRT
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
16525139
Citation
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.
Results Reference
result
PubMed Identifier
27581518
Citation
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.
Results Reference
derived
PubMed Identifier
22689675
Citation
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.
Results Reference
derived
Links:
URL
http://myeloma.uams.edu
Description
Myeloma Institute for Research & Therapy website

Learn more about this trial

UARK 98-026 TT II: Multiple Myeloma Evaluating Anti-Angiogenesis With Thalidomide and Post-Transplant Consolidation Chemotherapy

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