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

November 14, 2008
July 10, 2014
January 2008
September 2014   (final data collection date for primary outcome measure)
  • 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 ]
  • Feasibility and toxicities of maintenance therapy [ Designated as safety issue: Yes ]
  • Overall survival [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00792142 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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 ]
Not Provided
Not Provided
 
Bortezomib, Thalidomide, and Dexamethasone After Melphalan and Stem Cell Transplant in Treating Patients With Stage I-III Multiple Myeloma
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

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.

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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Neurotoxicity
  • 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
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.
Interventions:
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
45
Not Provided
September 2014   (final data collection date for primary outcome measure)

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
Both
up to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00792142
06143, P30CA033572, CHNMC-06143, MILLENNIUM-06143, CDR0000624513
Yes
City of Hope Medical Center
City of Hope Medical Center
National Cancer Institute (NCI)
Principal Investigator: Firoozeh Sahebi, MD City of Hope Medical Center
City of Hope Medical Center
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP