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

NCT00792142 | Completed Phase 2 Results DMC

• 5 other identifiers: 06143P30CA033572CHNMC-06143MILLENNIUM-06143CDR0000624513
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm; Neurotoxicity

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Adverse Events

  All grade 3 and above treatment-related adverse events (AEs) during bortezomib/dexamethasone treatment cycles.

  After 4 months of maintenance therapy

• One Year Overall Survival

  One year overall survival estimated using the product-limit method of Kaplan and Meier. Defined as the percentage of patients alive at year one after starting treatment.

  From date of treatment initiation until death from any cause, assessed up to one year.

Secondary Outcomes (2)

• Count of Response in Patients Started on Maintenance Therapy

  Post-Thalidomide at 1 year.

• One Year Progression-free Survival (PFS)

  From start of treatment initiation until disease progression, relapse or death from any cause, assessed up to 1 year.

Study Arms (1)

Treatment (stem cell transplant, maintenance treatment)

EXPERIMENTAL

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.

Drug: bortezomib; Drug: dexamethasone; Drug: melphalan; Drug: thalidomide; Genetic: cytogenetic analysis; Genetic: fluorescence in situ hybridization; Other: laboratory biomarker analysis; Other: questionnaire administration; Procedure: autologous hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation

Interventions

bortezomib DRUG

Given IV

Treatment (stem cell transplant, maintenance treatment)

dexamethasone DRUG

Given orally

Treatment (stem cell transplant, maintenance treatment)

melphalan DRUG

Given IV

Treatment (stem cell transplant, maintenance treatment)

thalidomide DRUG

Given orally

Treatment (stem cell transplant, maintenance treatment)

cytogenetic analysis GENETIC

Performed on baseline and post transplant bone marrow specimens

Treatment (stem cell transplant, maintenance treatment)

fluorescence in situ hybridization GENETIC

Performed on baseline and post transplant bone marrow specimens

Treatment (stem cell transplant, maintenance treatment)

laboratory biomarker analysis 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.

Treatment (stem cell transplant, maintenance treatment)

questionnaire administration 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.

Treatment (stem cell transplant, maintenance treatment)

autologous hematopoietic stem cell transplantation PROCEDURE

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

Treatment (stem cell transplant, maintenance treatment)

peripheral blood stem cell transplantation PROCEDURE

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

Treatment (stem cell transplant, maintenance treatment)

Eligibility Criteria

• Age: Up to 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010-3000, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell; Neurotoxicity Syndromes

Interventions

Bortezomib; Dexamethasone; Melphalan; Thalidomide; Cytogenetic Analysis; In Situ Hybridization, Fluorescence; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Nervous System Diseases; Poisoning; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; In Situ Hybridization; Staining and Labeling; Histocytological Preparation Techniques; Histological Techniques; Nucleic Acid Hybridization; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Paul Frankel, Ph.D.
• Organization: City of Hope

pfrankel@coh.org

626-218-5265

Study Officials

• Firoozeh Sahebi, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2008
• First Posted: November 17, 2008
• Study Start: January 16, 2008
• Primary Completion: April 21, 2014
• Study Completion: April 21, 2014
• Last Updated: August 19, 2021
• Results First Posted: September 17, 2020

Record last verified: 2020-01

Locations

US (1)