Combination High Dose Melphalan and Autologous Peripheral Blood Stem Cell (PBSC) Transplant With Bortezomib for Multiple Myeloma: A Dose and Schedule Finding Study

NCT ID: NCT00793650

Last Updated: 2012-08-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-05-31
• Study Completion Date: 2011-09-30

Brief Summary

The goal of this study is to evaluate the safety of melphalan and autologous PBSCT (peripheral blood stem cell transplantation - stem cells that come from your own body) in combination with bortezomib, a new FDA approved drug used to treat myeloma.

Conditions

Cancer; Multiple Myeloma

Keywords

Cancer; Multiple Myeloma; Peripheral Blood Stem Cell Transplant

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bortezomib before Melphalan

Enrolled patients were randomized to receive a single escalating dose of bortezomib (1.0, 1.3, or 1.6 mg/m2) 24 hours before melphalan.

Group Type: ACTIVE_COMPARATOR

Bortezomib

Intervention Type: DRUG

Escalating doses of bortezomib 1.0, 1.3, or 1.6 mg/m2 in Arm A and Arm B.

Melphalan

Intervention Type: DRUG

All patients received melphalan (100 mg/m^2/day × 2; days

-3 and -2), for a total dose of 200 mg/m^2.

Autologous PBSC Transplant

Intervention Type: PROCEDURE

Day 0 consists of the stem cell infusion.

Bortezomib after Melphalan

Enrolled patients were randomized to receive a single escalating dose of bortezomib (1.0, 1.3, or 1.6 mg/m2) 24 hours after melphalan.

Group Type: ACTIVE_COMPARATOR

Bortezomib

Intervention Type: DRUG

Escalating doses of bortezomib 1.0, 1.3, or 1.6 mg/m2 in Arm A and Arm B.

Melphalan

Intervention Type: DRUG

All patients received melphalan (100 mg/m^2/day × 2; days

-3 and -2), for a total dose of 200 mg/m^2.

Autologous PBSC Transplant

Intervention Type: PROCEDURE

Day 0 consists of the stem cell infusion.

Interventions

Bortezomib

Escalating doses of bortezomib 1.0, 1.3, or 1.6 mg/m2 in Arm A and Arm B.

Intervention Type: DRUG

Melphalan

All patients received melphalan (100 mg/m^2/day × 2; days

-3 and -2), for a total dose of 200 mg/m^2.

Intervention Type: DRUG

Autologous PBSC Transplant

Day 0 consists of the stem cell infusion.

Intervention Type: PROCEDURE

Other Intervention Names

Bortezomib or Velcade; Bortezomib or Velcade

Eligibility Criteria

Inclusion Criteria

• Patients with multiple myeloma who are eligible for an autologous peripheral blood progenitor transplant
• Male and female subjects between the age of 18 and 70 years.
• Patient has given informed consent prior to any study related procedures with the knowledge that consent can be withdrawn at anytime without prejudice to future medical care
• Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements
• Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
• Male subjects agrees to use an acceptable method for contraception for the duration of the study.
• Biopsy proven diagnosis of multiple myeloma from bone marrow aspirate and biopsy prior to study initiation
• Patient has achieved less than 90% disease reduction from previous treatment prior to transplant (as measured by serum or urine protein electrophoresis) and has more than 5% plasma cells in the bone marrow, or patient has progressed and has more than 5% plasma cells in the bone marrow.
• Karnofsky Performance Status score of ≥ 60%
• Patient has met the following laboratory requirements prior to Day -4
• Platelet count ≥ 50, 000/mm3
• Absolute Neutrophil Count ≥ 500/mm3
• Hemoglobin ≥ 10 g/dL (transfusion allowed to meet this criterion)
• Calculated creatinine clearance ≥ 30mL/min
• Toxic effects of previous therapy or surgery resolved to Grade 2 or better

Exclusion Criteria

• Unsupportable anemia with < 10b/dL
• Patient has a calculated or measured creatinine clearance of < 30mL/min within 14 days before enrollment
• Patient has ≥ Grade 2 peripheral neuropathy within 14 days before enrollment
• Patient has hypersensitivity to bortezomib, boron or mannitol
• Patient has had an allergic reaction to melphalan or chlorambucil
• Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
• Patient has received other investigational drugs with 14 days before enrollment
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study
• Cardiac or pulmonary dysfunction such that patients do not meet institutional pre-transplant evaluation criteria
• Known central nervous system involvement or suspicion of involvement with Myeloma
• Other active malignancies (with the exception of basal and squamous cell skin cancer) within 5 years of study entry. Patients with treated prostate or cervical cancer in situ who are 2 or more years from therapy and remain free of disease may be entered into the study at the investigator's discretion.
• Known to be HIV positive, HIV-1 positive

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Sagar Lonial

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sagar Lonial, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University Winship Cancer Institute

Locations

Emory University Winship Cancer Institute

Atlanta, Georgia, United States

Countries

United States

Other Identifiers

080-2005

Identifier Type: -

Identifier Source: org_study_id