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

Emory University

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Multiple Myeloma; Cancer

Treatments: Procedure: Autologous PBSC Transplant; Drug: Bortezomib; Drug: Melphalan

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00793650

080-2005

Details and patient eligibility

About

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.

Enrollment: 39 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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• Patient has given informed consent prior to any study related procedures with the knowledge that consent can be withdrawn at anytime without prejudice to future medical care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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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39 participants in 2 patient groups

Bortezomib before Melphalan

Active Comparator group

Description:

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.

Treatment:

Drug: Bortezomib

Drug: Melphalan

Procedure: Autologous PBSC Transplant

Bortezomib after Melphalan

Active Comparator group

Description:

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.

Treatment:

Drug: Bortezomib

Drug: Melphalan

Procedure: Autologous PBSC Transplant