Melphalan and Radiation Therapy Followed By Dexamethasone and Thalidomide in Treating Patients Who Are Undergoing Autologous Stem Cell Transplant for Stage I, Stage II, or Stage III Multiple Myeloma - Full Text View

Sponsors and Collaborators:	Beckman Research Institute National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00112827

Purpose

RATIONALE: Drugs used in chemotherapy, such as melphalan and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill cancer cells. Thalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy. Giving chemotherapy together with radiation therapy, thalidomide, and autologous stem cell transplant may allow more chemotherapy to be given so that more cancer cells are killed.

PURPOSE: This phase I/II trial is studying the side effects and best dose of radiation therapy when given together with high-dose melphalan followed by dexamethasone and thalidomide and to see how well they work in treating patients who are undergoing autologous stem cell transplant for stage I, stage II, or stage III multiple myeloma.

Condition	Intervention	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Biological: filgrastim Drug: cyclophosphamide Drug: dexamethasone Drug: melphalan Drug: thalidomide Procedure: autologous-autologous tandem hematopoietic stem cell transplantation Radiation: total marrow irradiation	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Tandem High-Dose Therapy With Melphalan & Total Marrow Irradiation (TMI) With PBPC Support & Dexamethasone/Thalidomide Maintenance

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Multiple Myeloma Radiation Therapy

Drug Information available for: Dexamethasone Cyclophosphamide Thalidomide Dexamethasone acetate Doxiproct plus Filgrastim Melphalan Sarcolysin Dexamethasone Sodium Phosphate Melphalan hydrochloride

U.S. FDA Resources

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

Primary Outcome Measures:

Feasibility at 3 years [ Designated as safety issue: No ]
Response rate at 3 years [ Designated as safety issue: No ]
Progresssion-free survival at 3 years [ Designated as safety issue: No ]
Overall survival at 3 years [ Designated as safety issue: No ]

Secondary Outcome Measures:

Assessment of cell biology [ Designated as safety issue: No ]

Estimated Enrollment:	86
Study Start Date:	October 2004
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the feasibility and toxic effects of tandem ablative therapy comprising high-dose melphalan and total marrow irradiation using helical tomotherapy in patients with stage I, II, or III multiple myeloma.
Determine the maximum tolerated dose of total marrow irradiation using helical tomotherapy in these patients.
Determine the response rate, progression-free survival, and overall survival of these patients after treatment with ablative therapy comprising high-dose melphalan and total marrow irradiation using helical tomotherapy followed by autologous peripheral blood stem cell transplantation and maintenance therapy comprising dexamethasone and thalidomide.
Determine the feasibility of maintenance therapy comprising dexamethasone and thalidomide in these patients.

Secondary

Correlate treatment outcome with cytogenetic, gene rearrangement, and fluorescence in situ hybridization studies of baseline and post-treatment bone marrow and blood specimens in these patients.

OUTLINE: This is a dose-escalation study of total marrow irradiation (TMI).

Priming and apheresis: Patients receive cyclophosphamide IV over 2 hours. Patients also receive filgrastim (G-CSF) IV or subcutaneously (SC) daily beginning 24 hours after the administration of cyclophosphamide and continuing until apheresis is complete. Patients undergo apheresis until an adequate number of peripheral blood stem cells (PBSC) are collected.
Ablative therapy:
- Course 1: Patients receive high-dose melphalan IV over 30 minutes on days -2 and -1. Patients then undergo autologous PBSC transplantation on day 0 and receive G-CSF IV or SC beginning on day 5 and continuing until blood counts recover.
- Course 2: Beginning 6-18 weeks later, patients undergo TMI once or twice daily on days -6 to -2. Patients then undergo autologous PBSC transplantation and receive G-CSF as in course 1. Cohorts of 3-6 patients receive escalating doses of TMI until the maximum tolerated dose (MTD) is determined.

The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.

Maintenance therapy: Beginning at least 30 days after day 0 of course 2 of ablative therapy, patients receive oral dexamethasone daily for 4 days and oral thalidomide daily for 28 days. Courses repeat every 28 days for approximately 12 months. Patients achieving a complete remission (CR) receive maintenance therapy for at least 6 months after achievement of CR. After completion of study treatment, patients are followed at 30 days, every 6 months for 1 year, and then annually for at least 2 years.

PROJECTED ACCRUAL: A total of 3-86 patients (3-36 for the phase I portion and 28-50 for the phase II portion) will be accrued for this study within approximately 3 years.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of multiple myeloma within the past 18 months
- Stage I-III disease
- Responsive disease OR stable disease
- Smoldering myeloma allowed provided there is evidence of progressive disease requiring therapy, as indicated by any of the following:
  - At least 25% increase in M protein levels or Bence Jones excretion
  - Hemoglobin ≤ 10.5 g/dL
  - Frequent infections
  - Hypercalcemia
  - Rise in serum creatinine above normal on two separate occasions
Non-quantifiable monoclonal proteins allowed provided other criteria for multiple myeloma or smoldering myeloma are met AND there is measurable or evaluable disease by radiographic means
No Waldenström's macroglobulinemia

PATIENT CHARACTERISTICS:

Age

18 to 70

Performance status

Karnofsky 70-100%

Life expectancy

Not specified

Hematopoietic

See Disease Characteristics
Absolute neutrophil count ≥ 1,000/mm^3
Platelet count ≥ 100,000/mm^3

Hepatic

Bilirubin ≤ 1.5 mg/dL
SGOT and SGPT < 2.5 times upper limit of normal
Hepatitis B antigen negative
Hepatitis C RNA negative

Renal

See Disease Characteristics
Creatinine clearance ≥ 50 mL/min

Cardiovascular

Ejection fraction ≥ 50% by MUGA and/or echocardiogram

Pulmonary

FEV1 > 60%
DLCO > 50% of predicted lower limit

Other

Not pregnant
Negative pregnancy test
Fertile patients must use effective double-method contraception for ≥ 4 weeks before, during, and for ≥ 4 weeks after study participation
Able to lie supine in a full-body cast for approximately 30 minutes
Able to undergo collection of ≥ 4 x 10^6 CD34+ cells/kg by apheresis
No other medical or psychosocial problem that would preclude study treatment
No other malignancy within the past 3 years except nonmelanoma skin cancer, carcinoma in situ of the cervix, or other cancer in complete remission for ≥ 2 years
No known hypersensitivity to filgrastim (G-CSF) or E. coli-derived proteins

PRIOR CONCURRENT THERAPY:

Biologic therapy

At least 3 weeks since prior thalidomide

Chemotherapy

At least 3 weeks since prior chemotherapy

Endocrine therapy

At least 3 weeks since prior steroids

Radiotherapy

At least 3 weeks since prior radiotherapy
No prior radiotherapy to > 20% of bone marrow or to any area exceeding 2,000 cGy

Surgery

Not specified

Other

At least 2 weeks since prior bisphosphonates
- Bisphosphonates may be resumed within 30-60 days after day 0 of study course 2

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00112827

Locations

United States, California
City of Hope Comprehensive Cancer Center	Recruiting
Duarte, California, United States, 91010-3000
Contact: Clinical Trials Office - City of Hope Comprehensive Cancer Cen 800-826-4673 becomingapatient@coh.org

Sponsors and Collaborators

Beckman Research Institute

National Cancer Institute (NCI)

More Information

Additional Information:

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

No publications provided

Responsible Party:	City of Hope Comprehensive Cancer Center ( George Somlo )
Study ID Numbers:	CDR0000428410, CHNMC-04064
Study First Received:	June 2, 2005
Last Updated:	June 30, 2009
ClinicalTrials.gov Identifier:	NCT00112827 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Anti-Inflammatory Agents
Dexamethasone
Anti-Infective Agents
Melphalan
Thalidomide
Immunologic Factors
Blood Protein Disorders
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Paraproteinemias
Cyclophosphamide
Hemostatic Disorders
Hormones
Anti-Bacterial Agents

Hemorrhagic Disorders
Alkylating Agents
Dexamethasone acetate
Immunoproliferative Disorders
Antineoplastic Agents, Hormonal
Hematologic Diseases
Blood Coagulation Disorders
Vascular Diseases
Angiogenesis Inhibitors
Immunosuppressive Agents
Glucocorticoids
Multiple Myeloma
Antineoplastic Agents, Alkylating
Peripheral Nervous System Agents
Lymphoproliferative Disorders

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Dexamethasone
Anti-Infective Agents
Melphalan
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
Growth Substances

ClinicalTrials.gov processed this record on August 30, 2009