Bortezomib, Thalidomide, and Dexamethasone After Melphalan and Stem Cell Transplant in Treating Patients With 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:	NCT00792142

Purpose

RATIONALE: Bortezomib and thalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. Bortezomib may also stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving bortezomib together with thalidomide and dexamethasone may kill any cancer cells that remain after high-dose melphalan and stem cell transplant in patients with multiple myeloma.

PURPOSE: This phase II trial is studying the side effects of giving bortezomib together with thalidomide and dexamethasone after melphalan and stem cell transplant and to see how well it works in treating patients with stage I, stage II, or stage III multiple myeloma.

Condition	Intervention	Phase
Cancer-Related Problem/Condition Multiple Myeloma and Plasma Cell Neoplasm	Drug: bortezomib Drug: dexamethasone Drug: melphalan Drug: thalidomide Procedure: autologous hematopoietic stem cell transplantation Procedure: cytogenetic analysis Procedure: fluorescence in situ hybridization Procedure: laboratory biomarker analysis Procedure: peripheral blood stem cell transplantation Procedure: questionnaire administration	Phase II

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Multiple Myeloma

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

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase II Study of Maintenance Treatment With Sequential Bortezomib, Thalidomide and Dexamethasone Following Autologous Peripheral Blood Stem Cell Transplant in Patients With Multiple Myeloma

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

Primary Outcome Measures:

Feasibility and toxicities of maintenance therapy [ Designated as safety issue: Yes ]
Overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Complete response rate [ Designated as safety issue: No ]
Duration of response [ Designated as safety issue: No ]
3-year progression-free survival [ Designated as safety issue: No ]

Estimated Enrollment:	45
Study Start Date:	January 2008
Estimated Primary Completion Date:	September 2012 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

To assess the feasibility and toxicities of maintenance therapy with sequential bortezomib, thalidomide, and dexamethasone after high-dose melphalan and autologous peripheral blood stem cell transplantation in patients with multiple myeloma.
To assess whether administration of sequential bortezomib, thalidomide, and dexamethasone can improve progression-free survival of these patients.

Secondary

To assess whether administration of sequential bortezomib, thalidomide, and dexamethasone can increase complete remission rate and duration of response in these patients.
To assess the impact of maintenance therapy with sequential bortezomib, thalidomide, and dexamethasone after transplantation on overall survival of these patients.
To evaluate the influence of cytogenetic abnormalities (e.g., chromosome 13 deletion, 14 q32 abnormality, t [4;14], chromosome 1 q21 amplification, and chromosome 17 deletion) on outcome by performing conventional cytogenetic study and fluorescence in situ hybridization (FISH) studies on baseline and post-transplant bone marrow specimens.

OUTLINE:

High-dose melphalan and autologous peripheral blood stem cell transplantation (PBSCT): Patients receive high-dose melphalan IV over 30 minutes on days -2 and -1 and undergo autologous PBSCT on day 0. Patients receive filgrastim (G-CSF) IV or subcutaneously beginning on day 5 and continuing until blood counts recover.
Maintenance therapy: Beginning 4-8 weeks after transplantation, patients receive bortezomib IV on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive oral dexamethasone on days 1-4; treatment with dexamethasone repeats every month for 12 months in the absence of disease progression or unacceptable toxicity. Beginning 2 weeks after completion of bortezomib, patients receive oral thalidomide once daily until disease progression.

Patients complete the FACT-GOG neurotoxicity questionnaire periodically. Bone marrow samples are collected at baseline and post-transplant for cytogenetic analysis by FISH.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of symptomatic multiple myeloma
- Stage II or III disease OR progressive stage I disease requiring chemotherapy and/or radiation therapy
- Diagnosis confirmed by both Salmon-Durie classification and International Staging System
Patients with non-secretory myeloma should have measurable serum free-light chain protein by the Free-lite test OR measurable disease such as a soft tissue myeloma
Not eligible for tandem transplant study using total marrow irradiation because of previous radiation or eligibility criteria
No evidence of disease progression (with ≥ 25% increase in M protein) on bortezomib and or thalidomide therapy before transplantation
A minimum of 4 x 10^6 of CD 34 + cells/kg has been harvested
- No contraindication to collection by apheresis

PATIENT CHARACTERISTICS:

Karnofsky performance status 70-100% (unless impaired due to bone disease)
Bilirubin ≤ 1.5 mg/dL
SGOT and SGPT < 2.5 times upper limit of normal
Creatinine clearance ≥ 40 mL/min
Absolute neutrophil count > 1,000/mm³
Platelet count > 100,000/mm³
Cardiac ejection fraction ≥ 45% by MUGA scan and/or echocardiogram
DLCO ≥ 50% of predicted lower limit
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective dual-method contraception
HIV negative
No other medical or psychosocial problems that, in the opinion of the primary physician or principal investigator, would place the patient at unacceptably high risk from this treatment regimen
No peripheral neuropathy ≥ grade 2
No history of hypersensitivity to bortezomib, boron, or mannitol

PRIOR CONCURRENT THERAPY:

See Disease Characteristics

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00792142

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)

Investigators

Principal Investigator:

Firoozeh Sahebi, MD

Beckman Research Institute

More Information

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

Responsible Party:	Kaiser Permanente Medical Center - Los Angeles ( Firoozeh Sahebi )
Study ID Numbers:	CDR0000624513, CHNMC-06143, MILLENNIUM-06143
Study First Received:	November 14, 2008
Last Updated:	December 9, 2008
ClinicalTrials.gov Identifier:	NCT00792142
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Dexamethasone
Melphalan
Immunoproliferative Disorders
Thalidomide
Neurotoxicity Syndromes
Blood Protein Disorders
Hematologic Diseases
Blood Coagulation Disorders
Bortezomib
Neurotoxicity syndromes

Vascular Diseases
Paraproteinemias
Hemostatic Disorders
Multiple Myeloma
Hemorrhagic Disorders
Multiple myeloma
Lymphoproliferative Disorders
Dexamethasone acetate
Neoplasms, Plasma Cell

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Anti-Infective Agents
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Hormones
Anti-Bacterial Agents
Therapeutic Uses
Cardiovascular Diseases
Growth Inhibitors
Angiogenesis Modulating Agents
Alkylating Agents

Neoplasms by Histologic Type
Immune System Diseases
Antineoplastic Agents, Hormonal
Growth Substances
Gastrointestinal Agents
Enzyme Inhibitors
Angiogenesis Inhibitors
Glucocorticoids
Immunosuppressive Agents
Pharmacologic Actions
Protease Inhibitors
Neoplasms
Autonomic Agents
Myeloablative Agonists
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on January 15, 2009