Thalidomide, Chemotherapy, and Peripheral Stem Cell Transplant in Treating Patients With Multiple Myeloma - Full Text View

Sponsor:	Southwest Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00040937

Purpose

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.

Condition	Intervention	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Biological: filgrastim Biological: sargramostim Drug: cyclophosphamide Drug: dexamethasone Drug: melphalan Drug: prednisone Drug: thalidomide Procedure: peripheral blood stem cell transplantation	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase II Trial Of Thalidomide/Dexamethasone Induction Followed By Tandem Melphalan Transplant And Prednisone/Thalidomide Maintenance (A BMT Study)

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Efficacy [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]
Safety [ Designated as safety issue: Yes ]
Correlation of chromosome 13 abnormalities with therapeutic response [ Designated as safety issue: No ]
Correlation of chromosome aberrations with event-free survival and overall survival [ Designated as safety issue: No ]
Immune reconstitution and recovery [ Designated as safety issue: No ]

Study Start Date:

June 2002

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00040937

Show 141 Study Locations

Sponsors and Collaborators

Southwest Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Mohamad A. Hussein, MD

The Cleveland Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Hussein MA, Bolejack V, Zonder JA, Durie BG, Jakubowiak AJ, Crowley JJ, Barlogie B. Phase II Study of Thalidomide Plus Dexamethasone Induction Followed by Tandem Melphalan-Based Autotransplantation and Thalidomide-Plus-Prednisone Maintenance for Untreated Multiple Myeloma: A Southwest Oncology Group Trial (S0204). J Clin Oncol. 2009 Jun 22; [Epub ahead of print]

Hussein MA, Jakubowiak AJ, Bolejack V, et al.: S0204: melphalan (MEL)-based tandem autotransplants (TAT) for multiple myeloma (MM) with thalidomide/dexamethasone (TD) induction and thalidomide/prednisone (TP) maintenance: a phase II trial of the Southwest Oncology Group. [Abstract] Blood 108 (11): A-3088, 2006.

Study ID Numbers:	CDR0000069421, SWOG-S0204
Study First Received:	July 8, 2002
Last Updated:	July 10, 2009
ClinicalTrials.gov Identifier:	NCT00040937 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Dexamethasone
Anti-Infective Agents
Melphalan
Prednisone
Molecular Mechanisms of Pharmacological Action
Thalidomide
Immunologic Factors
Antineoplastic Agents
Blood Protein Disorders
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Paraproteinemias
Cyclophosphamide

Hemostatic Disorders
Hormones
Anti-Bacterial Agents
Hemorrhagic Disorders
Therapeutic Uses
Cardiovascular Diseases
Growth Inhibitors
Angiogenesis Modulating Agents
Alkylating Agents
Dexamethasone acetate
Immunoproliferative Disorders
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Hematologic Diseases

ClinicalTrials.gov processed this record on November 27, 2009