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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00792142
First received: November 14, 2008
Last updated: July 10, 2014
Last verified: July 2014
  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-III multiple myeloma.


Condition Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Neurotoxicity
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
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: 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

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Feasibility and toxicities of maintenance therapy [ Time Frame: After 4 months of maintenance therapy ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: 3 years after completion of maintenance therapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Complete response rate [ Time Frame: After 4 months of maintenance therapy ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: 3 years after completion of maintenance therapy ] [ Designated as safety issue: No ]
  • 3-year progression-free survival [ Time Frame: 3 years after completion of maintenance therapy ] [ Designated as safety issue: No ]

Estimated Enrollment: 45
Study Start Date: January 2008
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: bortezomib
Given IV
Drug: dexamethasone
Given orally
Drug: melphalan
Given IV
Drug: thalidomide
Given orally
Genetic: cytogenetic analysis
Performed on baseline and post transplant bone marrow specimens
Genetic: fluorescence in situ hybridization
Performed on baseline and post transplant bone marrow specimens
Other: 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.
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.
Procedure: autologous hematopoietic stem cell transplantation
Minimum dose of 2 X 10(6) CD34 + cells/kg day 0 after two days of treatment with Melphalan
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

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010-3000
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Firoozeh Sahebi, MD City of Hope Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT00792142     History of Changes
Other Study ID Numbers: 06143, P30CA033572, CHNMC-06143, MILLENNIUM-06143, CDR0000624513
Study First Received: November 14, 2008
Last Updated: July 10, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by City of Hope Medical Center:
neurotoxicity
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma

Additional relevant MeSH terms:
Neoplasms
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Neurotoxicity Syndromes
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Nervous System Diseases
Poisoning
Substance-Related Disorders
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Bortezomib
Melphalan
Thalidomide
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics

ClinicalTrials.gov processed this record on July 24, 2014