Total Marrow Irradiation With High Dose Melphalan Prior to Autologous Transplant for Relapsed or Refractory Multiple Myeloma (BMT-03)

Study Overview
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Brief Summary
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In this phase I trial, patients with relapsed or refractory 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 9Gy.

Official Title
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BMT-03: A Phase I Trial of Total Marrow Irradiation in Addition to High Dose Melphalan Conditioning Prior to Autologous Transplant for Patients With Relapsed or Refractory Multiple Myeloma

Conditions
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Multiple Myeloma, Relapsed, Multiple Myeloma, Refractory to Standard Treatment

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients meeting criteria for symptomatic myeloma Patients who have progressive myeloma following initial induction (patients may have received any number of treatment regimens including prior autologous transplant) 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 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 allogeneic stem cell 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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Increasing doses of Total Marrow Irradiation (TMI), 3 Gy, 6 Gy, and 9 Gy.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1Total Marrow Irradiation (TMI) 3Gy<br>3Gy with standard high dose melphalan prior to autologous stem cell rescue | Radiation: Total Marrow Irradiation<br>* Subjects in this trial will receive total marrow irradiation 3Gy per day for up to four days and as little as one day<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®;Procedure: Autologous transplant<br>* Subjects will receive standard melphalan 200mg/m^2 (100mg/m^2 day-2 and day-1) conditioning with autologous stem cell rescue<br>|
| Experimental: Cohort 2 Total Marrow Irradiation (TMI) 6Gy<br>6Gy with standard high dose melphalan prior to autologous stem cell rescue | Radiation: Total Marrow Irradiation<br>* Subjects in this trial will receive total marrow irradiation 6Gy per day for up to four days and as little as one day<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®;Procedure: Autologous transplant<br>* Subjects will receive standard melphalan 200mg/m^2 (100mg/m^2 day-2 and day-1) conditioning with autologous stem cell rescue<br>|
| Experimental: Cohort 3 Total Marrow Irradiation (TMI) 9Gy<br>9Gy with standard high dose melphalan prior to autologous stem cell rescue | Radiation: Total Marrow Irradiation<br>* Subjects in this trial will receive total marrow irradiation 9Gy per day for up to four days and as little as one day<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®;Procedure: Autologous transplant<br>* Subjects will receive standard melphalan 200mg/m^2 (100mg/m^2 day-2 and day-1) conditioning with autologous stem cell rescue<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose of TMI | 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 for relapsed/ refractory myeloma. | Up to 60 days post-transplant. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | To evaluate progression free survival (PFS) and in patients with multiple myeloma (relapsed or refractory) 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, Relapsed, Refractory, Progressive Disease, Symptomatic