S0204 Thalidomide, Chemotherapy, and Peripheral Stem Cell Transplant in Treating Patients With Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00040937
First received: July 8, 2002
Last updated: June 12, 2013
Last verified: June 2013

July 8, 2002
June 12, 2013
June 2002
October 2008   (final data collection date for primary outcome measure)
Overall Survival [ Time Frame: 4-7 years ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00040937 on ClinicalTrials.gov Archive Site
Assess Toxicity of Thalidomide/Dexamethasone as a Pre-transplant Induction Regimen. [ Time Frame: Induction ] [ Designated as safety issue: Yes ]
To assess Grade 3-5 AE related to thalidomide/dexamethasone when administered as a pre-transplant induction regimen.
Not Provided
Not Provided
Not Provided
 
S0204 Thalidomide, Chemotherapy, and Peripheral Stem Cell Transplant in Treating Patients With Multiple Myeloma
A Phase II Trial Of Thalidomide/Dexamethasone Induction Followed By Tandem Melphalan Transplant And Prednisone/Thalidomide Maintenance (A BMT Study)

RATIONALE: Thalidomide may stop the growth of cancer cells by stopping blood flow to the cancer. Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplant may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Giving thalidomide before and after peripheral stem cell transplant may be effective in treating newly diagnosed multiple myeloma.

PURPOSE: This phase II trial is studying how well giving thalidomide with chemotherapy and peripheral stem cell transplant work in treating patients with newly diagnosed multiple myeloma.

OBJECTIVES:

  • Determine the efficacy and toxicity of thalidomide and dexamethasone as a pre-transplantation induction regimen in patients with multiple myeloma.
  • Determine, preliminarily, the safety and efficacy of prednisone and thalidomide maintenance therapy in these patients.
  • Correlate chromosome 13 abnormalities with therapeutic response in patients treated with this regimen.
  • Correlate specific subsets of chromosome aberrations with event-free and overall survival of patients treated with this regimen.
  • Evaluate immune reconstitution and recovery after first and second transplantation in these patients.

OUTLINE: This is a multicenter study.

  • Induction chemotherapy: Patients receive oral thalidomide once daily on days 1-35 and oral dexamethasone once daily on days 1-4, 9-12, and 17-20. Treatment repeats every 35 days for 3 courses in the absence of disease progression or unacceptable toxicity.
  • Stem cell mobilization and collection: Beginning 5-7 days, but no more than 3 weeks, after completion of induction chemotherapy, patients receive cyclophosphamide IV over 45-60 minutes on day 0, filgrastim (G-CSF) subcutaneously (SC) on days 1-10, and sargramostim (GM-CSF) SC beginning on day 1 and continuing until completion of peripheral blood stem cell (PBSC) collection. Patients begin PBSC collection on day 11 or as soon as blood counts recover.
  • First transplantation: Within 3-6 weeks after cyclophosphamide administration, patients receive melphalan IV over 20 minutes on day -1. Patients undergo PBSC infusion on day 0. Patients receive GM-CSF SC or IV beginning on day 6 and continuing until blood counts recover.
  • Second transplantation: Between 2-4 months after first transplantation, patients undergo a second tandem melphalan and PBSC transplantation with GM-CSF support as above.
  • Maintenance therapy: Beginning 70-90 days post-transplantation, patients receive oral prednisone every other day and oral thalidomide once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 12 months for 10 years.

PROJECTED ACCRUAL: Approximately 99 patients will be accrued for this study within 18 months.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Multiple Myeloma
  • Biological: filgrastim
    PBSC collection: 10 mcg/kg SQ days 1-10
    Other Name: G-CSF
  • Biological: sargramostim

    PBSC collection: 500 mcg/m2 SQ day 1 through last apheresis

    1st and 2nd trans: 500 mcg SC or IV days 6-WBC recovery

    Other Name: GM-CSF
  • Drug: cyclophosphamide
    PBSC collection: 1 mg/m2 IV over 45-60 mins day 0
    Other Name: cytoxan
  • Drug: dexamethasone
    40 mg/d PO days 1-4, 9-12, 17-20
    Other Name: decadron
  • Drug: melphalan
    1. st trans: 140 mg/m2 IV over 20 mins day -1
    2. nd trans: 200mg/m2 IV over 20 mins day -1
    Other Name: melphalan
  • Drug: prednisone
    maint: 50 mg/d PO every other day until progression
    Other Name: steroid
  • Drug: thalidomide
    ind: 50 mg increased by 50 mg every week to max 400 mg PO qhs for 35 days maint: 50 mg/d increased by 50 mg every week to 200 mg PO daily until progression
    Other Name: thalomid
  • Procedure: peripheral blood stem cell transplantation
    2-4 x 10^6/kg IV day 0
    Other Name: stem cell transplant
Experimental: treatment arm
thalidomide/dexamethasone followed by tandem melphalan peripheral blood stem cell transplantation (with cyclophosphamide and filgrastim or sargramostim support) and prednisone/thalidomide maintenance
Interventions:
  • Biological: filgrastim
  • Biological: sargramostim
  • Drug: cyclophosphamide
  • Drug: dexamethasone
  • Drug: melphalan
  • Drug: prednisone
  • Drug: thalidomide
  • Procedure: peripheral blood stem cell transplantation

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
147
October 2015
October 2008   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Newly diagnosed multiple myeloma requiring treatment

    • Smoldering myeloma with evidence of progressive disease requiring chemotherapy

      • More than 25% increase in M component levels and/or Bence-Jones excretion or symptom development
    • Non-secretory patients with at least 30% bone marrow plasmacytosis
  • No IgM peaks unless there is evidence of more than 30% bone marrow plasmacytosis or more than 3 lytic lesions

PATIENT CHARACTERISTICS:

Age

  • 18 to 65

Performance status

  • Zubrod 0-2 OR
  • Zubrod 3-4 based solely on bone pain

Life expectancy

  • Not specified

Hematopoietic

  • No untreated, unresolved symptomatic hyperviscosity

Hepatic

  • Hepatitis B negative

Renal

  • Creatinine no greater than 3 mg/dL if in renal failure and on dialysis (after hydration and/or correction of hypercalcemia)

Cardiovascular

  • No history of chronic cerebrovascular accident
  • No myocardial infarction within the past 6 months
  • No unstable angina
  • No congestive heart failure that is difficult to control
  • No uncontrollable hypertension
  • No cardiac arrhythmia that is difficult to control

Pulmonary

  • No history of chronic obstructive or chronic restrictive pulmonary disease
  • No untreated, unresolved pneumonia
  • Pulmonary function tests (PFTs) at least 50% of predicted
  • DLCO at least 50% of predicted
  • Arterial partial pressure of oxygen greater than 70 if unable to complete PFTs due to bone pain or fracture

Other

  • HIV negative
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
  • No untreated, unresolved pathologic fractures
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use at least 2 highly effective methods of contraception for 4 weeks before, during, and for at least 4 weeks after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No more than 8 weeks of prior thalidomide therapy

Chemotherapy

  • No prior chemotherapy for this disease

Endocrine therapy

  • Prior steroid therapy allowed provided treatment duration was no more than 2 weeks

Radiotherapy

  • No prior radiotherapy to more than 50% of the pelvis

Surgery

  • Not specified
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00040937
CDR0000069421, S0204, U10CA032102
Yes
Southwest Oncology Group
Southwest Oncology Group
National Cancer Institute (NCI)
Study Chair: Mohamad A. Hussein, MD The Cleveland Clinic
Southwest Oncology Group
June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP