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

NCT ID: NCT00792142

Last Updated: 2021-08-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-16
• Study Completion Date: 2014-04-21

Brief Summary

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.

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.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm; Neurotoxicity

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (stem cell transplant, maintenance treatment)

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.

Group Type: EXPERIMENTAL

bortezomib

Intervention Type: DRUG

Given IV

dexamethasone

Intervention Type: DRUG

Given orally

melphalan

Intervention Type: DRUG

Given IV

thalidomide

Intervention Type: DRUG

Given orally

cytogenetic analysis

Intervention Type: GENETIC

Performed on baseline and post transplant bone marrow specimens

fluorescence in situ hybridization

Intervention Type: GENETIC

Performed on baseline and post transplant bone marrow specimens

laboratory biomarker analysis

Intervention Type: OTHER

Baseline, post transplant and prior to start of bortezomib, every 3 months post transplant for the first year, after 6 cycles of bortezomib, every year after transplant for 2-4 years.

questionnaire administration

Intervention Type: OTHER

Completed at baseline (within 6 weeks prior to enrollment) and at 2 months post transplant and once a month after that for the first year. For the second year the questionnaire will be completed every 3 months as long as on thalidomide for the duration of the study.

autologous hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

Minimum dose of 2 X 10(6) CD34 + cells/kg day 0 after two days of treatment with Melphalan

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Minimum dose of 2 X 10(6) CD34 + cells/kg day 0 after two days of treatment with Melphalan

Interventions

bortezomib

Given IV

Intervention Type: DRUG

dexamethasone

Given orally

Intervention Type: DRUG

melphalan

Given IV

Intervention Type: DRUG

thalidomide

Given orally

Intervention Type: DRUG

cytogenetic analysis

Performed on baseline and post transplant bone marrow specimens

Intervention Type: GENETIC

fluorescence in situ hybridization

Performed on baseline and post transplant bone marrow specimens

Intervention Type: GENETIC

laboratory biomarker analysis

Baseline, post transplant and prior to start of bortezomib, every 3 months post transplant for the first year, after 6 cycles of bortezomib, every year after transplant for 2-4 years.

Intervention Type: OTHER

questionnaire administration

Completed at baseline (within 6 weeks prior to enrollment) and at 2 months post transplant and once a month after that for the first year. For the second year the questionnaire will be completed every 3 months as long as on thalidomide for the duration of the study.

Intervention Type: OTHER

autologous hematopoietic stem cell transplantation

Minimum dose of 2 X 10(6) CD34 + cells/kg day 0 after two days of treatment with Melphalan

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Minimum dose of 2 X 10(6) CD34 + cells/kg day 0 after two days of treatment with Melphalan

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Firoozeh Sahebi, MD

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Locations

City of Hope Medical Center

Duarte, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CHNMC-06143

Identifier Type: -

Identifier Source: secondary_id

MILLENNIUM-06143

Identifier Type: -

Identifier Source: secondary_id

CDR0000624513

Identifier Type: REGISTRY

Identifier Source: secondary_id

06143

Identifier Type: -

Identifier Source: org_study_id