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

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

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.

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.

Inclusion Criteria:

1. Multiple myeloma newly diagnosed with deletion 17p or translocation 4;14 or multiple myeloma with 1. or 2. relapse after autologous stem cell transplantation
2. Patients age: 18 - 65 years at time of inclusion (female and male)
3. Performance status ECOG < 2
4. Availability of haploidentical, matched or mismatched related or unrelated donor
5. Patients understand and voluntarily sign an informed consent
6. 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).
7. 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:

1. Severe active infection or other uncontrolled severe conditioning

2. 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

3. Positive serology for HIV

4. Pregnant or lactating women (positive serum pregnancy test)

5. Women of child-bearing potential with unclear contraception

6. Age < 18 and > 65 years.

7. Uncontrolled invasive fungal infection at time of screening (baseline)

8. Serious psychiatric or psychological disorders

9. Participation in another study with ongoing use of unlicensed investigational product from 28 days before study enrollment