Cyclophosphamide as Graft-versus-host Prophylaxis After Allogeneic Stem Cell Transplantation for Multiple Myeloma

Study Overview
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Brief Summary
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The present study is a multicenter, prospective phase II-study to evaluate the chronic GvHD and progression-free survival at 2 years after after allogeneic stem cell transplantation for patients with multiple myeloma.

Detailed Description
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The present study is a multicenter, prospective Phase II-study to evaluate the incidence of acute and chronic graft-versus-host disease at 2-years, the 2-year risk of non-relapse mortality, the 2-year progressive-free, and overall survival in patients with multiple myeloma who received a toxicity-reduced conditioning regimen combined of thiotepa and busulfan followed by allogeneic stem cell transplantation from matched or mismatched, related/unrelated and haploidentical donor, and cyclophosphamide as post-transplant GvHD prophylaxis in comparision to a historical group. In this study will further determine toxicity and safety of cyclophosphamide as GvHD prophylaxis.

Official Title
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Cyclophosphamide as Graft-versus-host Prophylaxis After Allogeneic Stem Cell Transplantation for Multiple Myeloma. A Phase II Study (Allo-MM-PostCy-Study)

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Multiple myeloma newly diagnosed with deletion 17p or translocation 4;14 or multiple myelo-ma with 1. or 2. relapse after autologous stem cell transplantation Patients age: 18 - 65 years at time of inclusion (female and male) Performance status ECOG < 2 Availability of haploidentical, matched or mismatched relative or unrelated donor Patients understand and voluntarily sign an informed consent The study population includes female of childbearing potential (FOCP). FOCP have to agree to comply with the applicable contraceptive requirements of the protocol as named below for the duration of the study and 6 months after end of study or having post-menopausal status or be permanently sterilized (at least 6 weeks post-sterilization). Men who are sexually active with FOCP must be instructed to use male contraception (condom) in order to avoid exposure of an existing embryo/fetus. Contraception should be continued until 6 months after end of study. Exclusion Criteria: Severe active infection or other uncontrolled severe conditioning Severe renal, hepatic, pulmonary or cardiac disease, such as: Total bilirubin, SGPT or SGOT > 3 times upper the normal level Left ventricular ejection fraction < 30 % Creatinine clearance < 30 ml/min DLCO < 35 % and/or receiving supplementary continuous oxygen Positive serology for HIV Pregnant or lactating women (positive serum pregnancy test) Women of child-bearing potential with unclear contraception Age < 18 and > 65 years. Uncontrolled invasive fungal infection at time of screening (baseline) Serious psychiatric or psychological disorders Participation in another study with ongoing use of unlicensed investigational product from 28 days before study enrollment

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
Interventional Model Description: All patients will receive on day 3 and 4 after allogeneic stem cell transplan-tation 50 mg/kg BW cyclophosphamide
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cyclophosphamid post Tranplant<br>Patients will receive on day 3 and 4 after allogeneic stem cell transplantation 50 mg/kg BW cyclophosphamide | Drug: Cyclophosphamide<br>* Patients will receive on day 3 and 4 after allogeneic stem cell transplantation 50 mg/kg BW cyclophosphamide<br>* Other names: Endoxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chronic GvHD | Chronic GvHD at 2 years after allogeneic SCT | 2 years | 
| Progression-free survival | Progression-free survival at 2 years after allogeneic SCT | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-relapsed mortality | Non-relapsed mortality at 2 years after allogeneic SCT | 2 years | 
| Acute GvHD | Incidence of acute GvHD on Day +100 after allogeneic SCT | Day +100 after allogeneic SCT | 
| Chronic GvHD | Incidence of chronic GvHD at 1 and 2 years after allogeneic SCT | 1 and 2 years after allogeneic SCT | 
| Toxicity | Toxicity scored according to NCI CTCAE, Version 4.0 | till 2 years | 
| Remission | Complete remission rate (including sCR and MRD negativity) | till 2 years | 
| Overall Survival | Overall survival at 2 years | 2 years | 
| Progression-free Survival | Progression-free survival at 2 years | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Without detection of deletion 17p or translocation 4;14;, Post Cyclophosphamide, GvHD Prophylaxis, Allogeneic SCT