Bortezomib, Thalidomide, and Dexamethasone After Melphalan and Stem Cell Transplant in Treating Patients With Stage I-III Multiple Myeloma

City of Hope

Status and phase

Completed

Phase 2

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Neurotoxicity

Treatments

Other: questionnaire administration

Genetic: cytogenetic analysis

Drug: melphalan

Other: laboratory biomarker analysis

Drug: bortezomib

Procedure: peripheral blood stem cell transplantation

Drug: thalidomide

Genetic: fluorescence in situ hybridization

Drug: dexamethasone

Procedure: autologous hematopoietic stem cell transplantation

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00792142

MILLENNIUM-06143

CDR0000624513 (Registry Identifier)

P30CA033572 (U.S. NIH Grant/Contract)

06143

CHNMC-06143

Details and patient eligibility

About

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-III multiple myeloma.

Full 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.

Enrollment

45 patients

Sex

All

Ages

Under 70 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Multiple Myeloma patients with symptomatic disease, stage II or III at diagnosis or progressive stage I requiring chemotherapy and/or radiation therapy (by Salmon-Durie classification), who are not eligible for tandem transplant study using TMI; because of previous radiation or eligibility criteria; documentation of disease staging by both Salmon-Durie classification and International Staging System (ISS) is required
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
A minimum of 4 x 10^6 of CD 34 Positive cell/kg has been harvested
A Karnofsky performance status (KPS) of >= 70% is required unless the KPS is impaired due to bone disease
No contraindication to the collection of a minimum of 4 x 10^6 CD34+ cells/kg by apheresis
All patients must have signed a voluntary, informed consent in accordance with institutional and federal guidelines
Bilirubin =< 1.5 mg/dl
Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvate transaminase (SGPT) < 2.5 x upper limits of normal
Creatinine clearance of >= 40cc/min
Absolute neutrophil count of > 1000/ul
Platelet count of > 100,000/ul
Cardiac ejection fraction >= 45% by multigated acquisition (MUGA) scan and/or by echocardiogram
Diffusing capacity of the lung for carbon monoxide (DLCO) >= 50% of predicted lower limit
Human immunodeficiency virus (HIV) antibody tests negative
No other medical, or psychosocial problems which in the opinion of the primary physician or principal investigator would place the patient at unacceptably high risk from this treatment regimen

Exclusion criteria

Presence of peripheral neuropathy >= grade II
Patients with evidence of disease progression (with >= 25% increase in M protein) on bortezomib and or thalidomide therapy prior to transplant
Pregnant or nursing women, as well as women of child bearing age, who are unwilling to use a dual method of contraception and men who are unwilling to use condom
Patients with history of hypersensitivity to bortezomib, boron or mannitol

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

45 participants in 1 patient group

Treatment (stem cell transplant, maintenance treatment)

Experimental group

Description:

Patients receive high-dose melphalan IV over 30 minutes on days -2 and -1 and undergo autologous peripheral blood stem cell transplantation on day 0. Patients receive filgrastim IV or SC beginning on day 5 and continuing until blood counts recover. Beginning 4 to 8 weeks after transplantation, patients receive maintenance therapy comprising 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 to 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.

Treatment: