DTPACE Followed by Tandem Transplant With Melphalan (MEL) 200 Versus MEL/Dexamethasone/Thalidomide (DT) Platinol/Adriamycin/Etoposide (PACE) Hybrid and DTPACE Consolidation
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Cisplatin; Cyclophosphamide; Adriamycin; Etoposide; Melphalan; Thalidomide; Dexamethasone
Intervention description: 20mg/m2 continuous infusion days -3 and -2.; 800 mg/m2 continuous infusion days -3 and -2.; 20mg/m2 continuous infusion -3 and -2.; 80mg/m2 continuous infusion -3 and -2.; 200 mg/m2 IV over <20 minutes on -1 on Arm 1. 50mg/m2 IV over 20 minutes days -3 and -2 on Arm 2.; 200mg PO Continuing to Day +5, then hold until platelets >50 thousand (K).; 40 mg po days 1 - 4 (4 days)
Intervention MeSH terms: Thalidomide; Dexamethasone; Cyclophosphamide; Melphalan; Cisplatin; Doxorubicin; Etoposide; Liposomal doxorubicin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 97.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Multiple Myeloma; DTPACE; Tandem Transplant; Cisplatin; Cyclophosphamide; Dexamethasone; Doxorubicin; Etoposide; Sargramostim; Thalidomide; Melphalan

Summary:

      The purpose of this study is to find out if transplant with a new regimen of chemotherapy
      called DT PACE-Melphalan is better than transplant with Melphalan alone. DT-PACE refers to a
      chemotherapy regimen for multiple myeloma consisting of Dexamethasone, Thalidomide, Cisplatin
      or Platinol, Adriamycin or doxorubicin, Cyclophosphamide, and Etoposide. Another purpose of
      this study is to find out if there will be fewer side effects with the new regimen of DT
      PACE-Melphalan, compared to melphalan alone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have 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, unless
             the left ventricular ejection fraction is > 55% on Multi-gated Acquisition Scan (MUGA)
             or Echocardiogram (ECHO). If the patient has had > 450 mg/m2 of prior adriamycin, the
             LVEF must be evaluated prior to every cycle of DT PACE and it must be > 55% for
             patient to continue to receive adriamycin.

          -  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 Southwest Oncology Group
             (SWOG) criteria. Patients with a poor performance status (3-4), based solely on bone
             pain, will be eligible.

          -  Patients must have a platelet count greater than or equal to 100,000/microliters.
             Patients with platelet count <100,000/microliters may be enrolled if it is felt to be
             due to extensive marrow plasmacytosis.

          -  Patients must have a creatinine <3 mg/dl and a creatinine clearance greater than or
             equal to 30 ml/minute. Patients with a creatinine clearance of 30-50 ml will only
             receive a 50% cisplatin dose.

          -  Patients must have adequate hepatic function defined as serum transaminases < 2 x
             Upper limit of normal (ULN) and direct bilirubin < 2.0 mg/dl.

          -  Patients must be able to receive full doses of DT PACE, in the opinion of the treating
             investigator, with some exception of: Patients that have received prior adriamycin >
             450 mg/m2 and left ventricular ejection fraction (LVEF) < 55% or patients with a
             creatinine clearance 30 - 50 ml/minute, who will receive 50% of the cisplatin dose.

          -  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 significant co-morbid medical conditions or uncontrolled life
             threatening infection.

          -  Patients must not have received a prior autotransplant or allograft.

          -  Patients with recent (less than or equal to 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
             must be greater than or equal to 50% and must be performed within 60 days prior to
             registration, unless the patient has received chemotherapy within that period of time
             (dexamethasone and thalidomide excluded), in which case the LVEF must be repeated.

          -  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.

          -  Pregnant or nursing women may not participate.

          -  Patients must not have significant co-morbid medical conditions or uncontrolled life
             threatening infection.

          -  Patients must not have a history of chronic obstructive or chronic restrictive
             pulmonary disease. Patients must have adequate pulmonary function studies greater than
             or equal to 50% of predicted on mechanical aspects (FEV1, forced vital capacity (FVC)
             and diffusion capacity (DLCO) greater than or equal to 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.