Busulfan Plus Melphalan Conditioning Regimen for Lymphoid Malignancies or Multiple Myeloma
Condition: Multiple Myeloma; Lymphoma
MeSH terms: Lymphoma; Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Busulfan; Melphalan
Intervention description: Test Dose = 32 mg/m^2 IV for 1 Day; 130 mg/m^2 IV for 4 Days; 70 mg/m^2 IV for 2 Days
Intervention MeSH terms: Melphalan; Busulfan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 168.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Multiple Myeloma; Hodgkin's Disease; Non-Hodgkin's Lymphoma; Leukemia; Lymphoma; Busulfan; Melphalan; Autologous bone marrow; BMT; Peripheral blood stem cell transplant; PBSCT

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.
    

Eligibility 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.