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D.T. PACE Versus High Dose Melphalan and Autologous Transplant in Patients With Previously Treated Multiple Myeloma

Primary Purpose

Multiple Myeloma

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Thalidomide
Sponsored by
University of Arkansas
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple Myeloma, D.T. PACE, Melphalan, Transplant, Thalidomide, Dexamethasone, Cisplatin, Cyclophosphamide, Doxorubicin, Etoposide, Filgrastim, Interferon-alpha 2b, Sargramostim

Eligibility Criteria

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

Inclusion Criteria: Patients must have previously treated (> 1 cycle prior therapy), active multiple myeloma requiring treatment. Patients that have received >450 mg/m2 of prior Adriamycin therapy are eligible, however, Adriamycin will be deleted from the DT PACE regimen in these patients. Patients must have measurable disease defined as one of the following: serum monoclonal protein >/= 1.0 mg/dl, OR urine monoclonal protein >/= 1.0 grams/24 hour, OR >/= 20% bone marrow plasmacytosis. All necessary baseline studies for determining eligibility must be obtained within 35 days prior to registration. 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 must have a platelet count > or = 100,000/microliters. Patients with platelet count < 100,000/microliters may be enrolled if it is felt to be due to extensive marrow plasmacytosis. The study coordinator must be consulted and dose modifications may apply. 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. Exclusion Criteria: Patients must not have received a prior autotransplant or allograft. Patients must not have significant co-morbid medical conditions or uncontrolled life threatening infection. Patients with recent (< o= 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.Patients must have adequate pulmonary function studies > or = 50% of predicted on mechanical aspects (FEV1, FVC, etc) and diffusion capacity (DLCO) > or = 50% of predicted. Patients unable to complete pulmonary function tests due to myeloma related pain or fracture must have a high resolution CT scan of the chest and must also have acceptable arterial blood gases defined as P02 greater than 70. 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 childbearing 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 an effective contraceptive method.

Sites / Locations

  • University of Arkansas for Medical Sciences/MIRT

Outcomes

Primary Outcome Measures

1.1 To evaluate, in a randomized phase III clinical trial in previously treated multiple myeloma patients whether angio-chemotherapy with D.T. PACE may be equivalent or superior to tandem transplant.

Secondary Outcome Measures

Full Information

First Posted
June 2, 2004
Last Updated
July 1, 2010
Sponsor
University of Arkansas
Collaborators
Celgene Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT00083876
Brief Title
D.T. PACE Versus High Dose Melphalan and Autologous Transplant in Patients With Previously Treated Multiple Myeloma
Official Title
UARK 98-035, A Phase III Study of D.T. PACE Versus High Dose Melphalan and Autologous Transplant in Patients With Previously Treated Multiple Myeloma
Study Type
Interventional

2. Study Status

Record Verification Date
July 2010
Overall Recruitment Status
Completed
Study Start Date
September 1998 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
November 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
University of Arkansas
Collaborators
Celgene Corporation

4. Oversight

5. Study Description

Brief Summary
This study has been designed to evaluate whether combination chemotherapy and "anti-angiogenesis" therapy with thalidomide is equal or superior to autologous transplantation for the treatment of multiple myeloma.
Detailed Description
All patients will receive two cycles, 4-6 weeks apart, of a combination of chemotherapy drugs (a regimen called D.T. PACE) and collection of peripheral blood stem cells. D.T. PACE consists of 6 chemotherapy drugs (Dexamethasone, Thalidomide, CisPlatin, Adriamycin, Cyclophoshamide, and Etoposide). Four to six weeks after the last cycle of D.T. PACE, each patient with no evidence of myeloma progression will be randomly assigned to receive 1) Autologous Transplant as described below or 2) Additional cycles of D.T. PACE. Since it is not known at this time which treatment is the best, patients will be placed by chance in one of the two groups. If tests show that myeloma is in remission at the time of randomization, 2 additional cycles of D.T. PACE will be given. If myeloma is not in remission, 2 additional cycles of D.T. PACE will be given, then the myeloma will be re-assessed. If the patients myeloma protein has decreased by 90% since baseline or better, 2 more cycles are given. If it has not decreased that much or has gotten worse, the patient will be offered autologous transplantation. Patients with no financial coverage for transplant, or those that have inadequate stem cell collections to support two transplants, will not be randomized and will proceed directly to treatment 2, continued D.T. PACE. If it is determined that the myeloma did not respond adequately to the first 2 cycles of D.T. PACE, then the patient will not be randomized and will proceed directly to autologous transplant. Between 2 and 4 months after the first PBSC transplant, the patient will undergo a second course of high-dose Melphalan and PBSC transplant. In order for all patients to receive the maximum possible benefit, patients may "cross-over" to the other treatment arm if the myeloma does not go into complete remission or at any time myeloma progresses after randomization. When the physician feels that the maximum benefit from chemotherapy has been received (best partial or complete remission) the last phase of the study will start, which is maintenance. Patients will be randomly assigned to receive either low dose (50 mg) or higher dose (200 mg) thalidomide with the dexamethasone.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Multiple Myeloma, D.T. PACE, Melphalan, Transplant, Thalidomide, Dexamethasone, Cisplatin, Cyclophosphamide, Doxorubicin, Etoposide, Filgrastim, Interferon-alpha 2b, Sargramostim

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
500 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Thalidomide
Primary Outcome Measure Information:
Title
1.1 To evaluate, in a randomized phase III clinical trial in previously treated multiple myeloma patients whether angio-chemotherapy with D.T. PACE may be equivalent or superior to tandem transplant.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have previously treated (> 1 cycle prior therapy), active multiple myeloma requiring treatment. Patients that have received >450 mg/m2 of prior Adriamycin therapy are eligible, however, Adriamycin will be deleted from the DT PACE regimen in these patients. Patients must have measurable disease defined as one of the following: serum monoclonal protein >/= 1.0 mg/dl, OR urine monoclonal protein >/= 1.0 grams/24 hour, OR >/= 20% bone marrow plasmacytosis. All necessary baseline studies for determining eligibility must be obtained within 35 days prior to registration. 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 must have a platelet count > or = 100,000/microliters. Patients with platelet count < 100,000/microliters may be enrolled if it is felt to be due to extensive marrow plasmacytosis. The study coordinator must be consulted and dose modifications may apply. 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. Exclusion Criteria: Patients must not have received a prior autotransplant or allograft. Patients must not have significant co-morbid medical conditions or uncontrolled life threatening infection. Patients with recent (< o= 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.Patients must have adequate pulmonary function studies > or = 50% of predicted on mechanical aspects (FEV1, FVC, etc) and diffusion capacity (DLCO) > or = 50% of predicted. Patients unable to complete pulmonary function tests due to myeloma related pain or fracture must have a high resolution CT scan of the chest and must also have acceptable arterial blood gases defined as P02 greater than 70. 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 childbearing 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 an effective contraceptive method.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Barthel 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
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

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D.T. PACE Versus High Dose Melphalan and Autologous Transplant in Patients With Previously Treated Multiple Myeloma

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