Total Marrow Irradiation and High-dose Melphalan for Double Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate if the use total marrow irradiation (TMI) as a sole preparation for the first autologous hematopoietic stem cell transplantation (autoHSCT) followed by high-dose melphalan used prior to second autoHSCT is safe and effective in patients with multiple myeloma (MM).

Detailed Description
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AutoHSCT is a standard treatment of patients with MM. According to soem clinical evidence double autoHSCT provides survival advantage compared to a single procedure. Most frequently used conditioning regimen consists pf high doses of melphalan (HD-MEL). In some studies it was used in combination with total body irradiation (TBI), which, however was associated with significant toxicity. In our center the standard procedure includes TBI as a single treatment at 1st autoHSCT and HD-Mel at 2nd autoHSCT. As in MM malignant plasma cells are localized almost exclusively in bone marrow there is rationale to limit irradiation to bones. For this purpose in the current study we substitute TBI with TMI. Additional boosts are provided for active sites of disease based on PET/CT imaging. Our intention is to minimize toxicity while maintaining the treatment efficacy.

Official Title
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Efficacy and Safety of Double Autologous Hematopoietic Stem Cell Transplantation With Sequential Use of Total Marrow Irradiation and High-dose Melphalan in Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Radiation: Total marrow irradiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-65 years Diagnosis of multiple myeloma PR, VGPR or CR at inclusion Performance status WHO 0-1 Written informed consent Exclusion Criteria: Organ dysfunction: elevated ALT, AST, bilirubin, AF; creatinine >1.5 upper normal limit; LVEF <45% Active infection Unstable diabetes Psychiatric diseases History of high-dose chemotherapy or irradiation Second malignancy Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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>Double autologous hematopoietic stem cell transplantation using TMI and HD-Mel | Radiation: Total marrow irradiation<br>* Mobilization of stem cells with the use of cytarabine 1.6 g/m2 followed by filgrastim 480 ug/d. Conditioning for the 1st autoHSCT: total marrow irradiation 4 Gy on days -3,-2,-1 (total 12 Gy). Conditioning for 2nd autoHSCT performed 3-4 months after the 1st one: melphalan 100 mg/m2 on days -2,-3 (total 200 mg/m2)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | three years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of complete and very good partial responses |  | six months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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autologous hematopoietic stem cell transplantation, total marrow irradiation, melphalan, multiple myeloma