Total Marrow Irradiation With High Dose Melphalan Prior to Autologous Transplant for Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Total Marrow Irradiation; Autologous Transplant; Melphalan; Filgrastim (G-CSF)
Intervention description: Subjects in this trial will receive total body irradiation (3Gy) per day for up to four days and as little as one day. Total IMT doses: 3Gy, 6Gy, 9Gy, or 12Gy.; Subjects will receive standard melphalan 200mg/m^2 (100mg/m^2 day-2 and day-1) conditioning with escalating doses of total marrow irradiation prior to autologous stem cell rescue.; Subjects will receive standard melphalan 200mg/m^2 (100mg/m^2 day-2 and day-1) conditioning therapy prior to transplant.; Subjects to begin GCSF 5 μg/kg/d SC or IV on Day 5 and continue until ANC > 1000/mm^3 over period of 3 days.
Intervention MeSH terms: Melphalan
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Multiple Myeloma; High Risk; Intermediate Risk; Symptomatic

Summary:

      In this phase I trial, patients with multiple myeloma will receive standard high dose
      melphalan with autologous stem cell rescue. In addition the pre-transplant conditioning will
      include targeted total marrow irradiation (TMI). This conventional 3+3 phase I trial will
      increase the dose of TMI until the maximum tolerated dose (MTD) is reached. Initial patients
      enrolled will receive the lowest possible dose of 3Gy. Maximum dose will be 12Gy.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients meeting criteria for symptomatic myeloma

          2. Patients must be high or intermediate risk of disease progression as defined by having
             one of the following criteria: 2.1 ISS stage 2 or 3 disease 2.2 Abnormal metaphase
             cytogenetics 2.3 Presence of FISH abnormalities aside from hyperdiploidy

          3. Patients who have received at least 2 cycles of systemic treatment of any kind in the
             preceding 12 months

          4. Patient age 18-75 years at time of enrollment

          5. Karnofsky performance status of ≥70

          6. Cardiac function: LVEF >40%

          7. Hepatic: Bilirubin <2x upper limit of normal and ALT and AST < 2.5x the upper limit of
             normal

          8. Renal: Creatinine clearance of ≥30mL/min, estimated or calculated

          9. Pulmonary: DLCO, FEV1, FVC >50% of predicted (after correction for hemoglobin)

        Exclusion Criteria:

          1. Patients with diagnosis of plasma cell leukemia

          2. Patients with myeloma who have had any disease progression prior to enrollment

          3. Patients with truly non secretory myeloma (patients with light chain disease are
             eligible)

          4. Pregnant or breast-feeding

          5. Uncontrolled viral, fungal or bacterial infection Note: Infection is permitted if
             there is evidence of response to medication. Eligibility of HIV infected patients will
             be determined on a case-by-case basis.

          6. Patients who have undergone prior allograft or autologous transplant

          7. Prior solid organ transplant

          8. Patients receiving prior radiation to more than 20% of bone marrow containing areas