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

This study has been completed.
Sponsor:
Collaborator:
Celgene Corporation
Information provided by:
University of Arkansas
ClinicalTrials.gov Identifier:
NCT00083876
First received: June 2, 2004
Last updated: July 1, 2010
Last verified: July 2010
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: Thalidomide
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of Arkansas:

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.

Estimated Enrollment: 500
Study Start Date: September 1998
Study Completion Date: November 2007
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00083876

Locations
United States, Arkansas
University of Arkansas for Medical Sciences/MIRT
Little Rock, Arkansas, United States, 72205
Sponsors and Collaborators
University of Arkansas
Celgene Corporation
Investigators
Principal Investigator: Barthel Barlogie, M.D., Ph.D. UAMS
  More Information

Additional Information:
No publications provided by University of Arkansas

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Edwina Mosby, CRA, University_of_Arkansas
ClinicalTrials.gov Identifier: NCT00083876     History of Changes
Other Study ID Numbers: UARK 98-035
Study First Received: June 2, 2004
Last Updated: July 1, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Arkansas:
Multiple Myeloma
D.T. PACE
Melphalan
Transplant
Thalidomide
Dexamethasone
Cisplatin
Cyclophosphamide
Doxorubicin
Etoposide
Filgrastim
Interferon-alpha 2b
Sargramostim

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Melphalan
Thalidomide
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors

ClinicalTrials.gov processed this record on September 14, 2014