Total Marrow Irradiation With High Dose Melphalan Prior to Autologous Transplant for Multiple Myeloma

Study Overview
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Brief Summary
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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.

Detailed Description
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To establish the maximal tolerated dose of total marrow irradiation which can be added to high dose melphalan conditioning in patients with multiple myeloma undergoing autologous stem cell transplant.

Official Title
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BMT-02: A Phase I Trial of Total Marrow Irradiation in Addition to High Dose Melphalan Conditioning Prior to Autologous Transplant for Multiple Myeloma Following Initial Induction Therapy

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Radiation: Total Marrow Irradiation
* Procedure: Autologous Transplant
* Drug: Melphalan
* Drug: Filgrastim (G-CSF)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients meeting criteria for symptomatic myeloma 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 Patients who have received at least 2 cycles of systemic treatment of any kind in the preceding 12 months Patient age 18-75 years at time of enrollment Karnofsky performance status of ≥70 Cardiac function: LVEF >40% Hepatic: Bilirubin <2x upper limit of normal and ALT and AST < 2.5x the upper limit of normal Renal: Creatinine clearance of ≥30mL/min, estimated or calculated Pulmonary: DLCO, FEV1, FVC >50% of predicted (after correction for hemoglobin) Exclusion Criteria: Patients with diagnosis of plasma cell leukemia Patients with myeloma who have had any disease progression prior to enrollment Patients with truly non secretory myeloma (patients with light chain disease are eligible) Pregnant or breast-feeding 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. Patients who have undergone prior allograft or autologous transplant Prior solid organ transplant Patients receiving prior radiation to more than 20% of bone marrow containing areas

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Total Marrow Irradiation<br>Escalating doses of total marrow irradiation (3Gy, 6Gy, 9Gy, or 12Gy) with standard high dose melphalan prior to autologous stem cell rescue. | Radiation: Total Marrow Irradiation<br>* 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.<br>Procedure: Autologous Transplant<br>* 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.<br>Drug: Melphalan<br>* Subjects will receive standard melphalan 200mg/m^2 (100mg/m^2 day-2 and day-1) conditioning therapy prior to transplant.<br>* Other names: Alkeran ®;Drug: Filgrastim (G-CSF)<br>* 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.<br>* Other names: Neupogen®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival No Results Due to 1 Subject Came Off Treatment Within 7 Days and 1 Subject Came Off Treatment Within 5 Days. Not Enough Data to Analyze | To evaluate progression free survival (PFS) and in patients with multiple myeloma undergoing autologous stem cell transplant using the combination of high dose melphalan and total marrow irradiation. | Up to 1 year post-transplant. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma, High Risk, Intermediate Risk, Symptomatic