Busulfan Plus Melphalan Conditioning Regimen for Lymphoid Malignancies or Multiple Myeloma

• Status: Completed
• Trial end date: 2010-11-01
• Target enrollment: 0
• Participant gender: All

Summary

Primary Objectives:

1. To determine the efficacy of administering multiple doses of intravenous (i.v.) busulfan at a dose of 130 mg/m2, to yield a systemic plasma drug exposure represented by a daily area under the plasma concentration versus time curve (AUC) of approximately 5,000 mMol-min for 4 days, followed by i.v. melphalan at a dose of 70 mg/m2 for 2 days in adult patients receiving autologous or allogeneic transplantation for lymphoid malignancies or myeloma.

2. To describe the plasma pharmacokinetic (PK) profiles of busulfan and melphalan in this regimen.

3. To determine the disease-free and overall survival of patients receiving this preparative regimen.

4. To determine the treatment-related morbidity and mortality of this combination of drugs.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Treatments: Busulfan; Melphalan

Criteria

Inclusion Criteria:

• Patients with lymphoid malignancies, including Hodgkin's and non-Hodgkin's lymphoma (primary refractory or recurrent), or multiple myeloma (beyond first complete remission or unresponsive to therapy. Complete remission for multiple myeloma defined by absence of detectable paraprotein in serum and/or urine by immunoelectrophoresis or immunofixation, and < 5% plasma cells in the bone marrow), not qualifying for treatment protocols of higher priority.

• Age 18 to 65 years of age.

• Adequate renal function as defined by estimated serum creatinine clearance > 50 ml/min and serum creatinine < 1.8 mg/dL.

• Adequate hepatic function, as defined by serum glutamic pyruvic transaminase (SGPT) < 3 * upper limit of normal; serum bilirubin and alkaline phosphatase < 2 * upper limit of normal, or considered not clinically significant.

• Adequate pulmonary function with Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and Capacity of the Lung for Carbon Monoxide (DLCO)> 50%. Exceptions may be allowed for patients with pulmonary involvement after discussing with principal investigator (PI).

• Adequate cardiac function with left ventricular ejection fraction >/= 40%. No uncontrolled arrhythmias or symptomatic cardiac disease.

• Zubrod performance score < 2.

• Patients receiving an allogeneic transplant must have an HLA matched, or one A, B, or DR mismatched related donor. Unrelated donor must be matched at A, B, and DR (defined as A, B serologic matched and DRB1 molecular matched). Donor must be willing to donate peripheral blood or bone marrow progenitor cells.

• Patient and donor should be willing to participate in the study by providing written consent.

• Female patient must not be pregnant and have negative pregnancy.

Exclusion Criteria:

• Patients with unresolved grade >/= 3 non-hematologic toxicity from previous therapy. Patients with grade 2 toxicity will be eligible at the discretion of the PI.

• Patients with active Central Nervous System (CNS) disease.

• Evidence of acute or chronic active hepatitis or cirrhosis. If positive hepatitis serology, discuss with Study Chairman and consider liver biopsy.

• Uncontrolled infection, including Human immunodeficiency virus (HIV) or Human T-lymphotropic virus Type I (HTLV-1) infection.

• Patients who have had a previous autologous or allogeneic stem cell transplant during the past year.