Graft Versus Host Disease
Conditions
Keywords
anti thymocyte globulin, cyclophospamide, graft-versus-host disease, stem cell transplantation
Brief summary
Investigators hypothesize that combination of ATLG with PTCy in matched or mismatched unrelated hematopoietic stem cell transplantation will reduce acute and chronic GVHD incidence. Furthermore it will allow shortening of the length of post-transplantation immunosuppression with calcineurin inhibitor (CNI) administration (currently administrated in addition to ATG as GVHD prophylaxis in daily common practice)
Interventions
DRUGCyclophosphamide
In the first phase escalated doses of post-transplant cyclophosphamide up to a maximal dose of 50 mg/kg , the second phase will use the MTD cyclophosphamide dose identified in the first phase.
DRUGanti-human T-lymphocyte immunoglobulin (ATLG)
15mg/kg total (5mg/kg day) on days -3 to -1 pre transplantation
Sponsors
Sheba Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The patients will get conventional GVHD prophylaxis consisting of ATLG 15mg/kg total (5mg/kg day) on days -3 to -1 pre transplantation. Cyclophosphamide at 25mg/kg dose will be administrated at day +3 post infusion of the stem cell (SC) graft to the first 3 patients. If no \> grade II toxicity\* occurs, the next 3 patients will receive cyclophosphamide at 25mg/kg dose at day +3 and +4 post SC graft infusion. If no \> grade II toxicity\*occurs, the next 3 patients will receive cyclophosphamide at 37.5 mg/kg dose at day +3 and +4 post SC graft infusion. If no \> grade II toxicity\* occurs, the next 3 patients will receive the target dose of cyclophosphamide at 50 mg/kg dose on day +3 and +4 post SC graft infusion. The residual 18 patients will receive cyclophosphamide at the maximal tolerated dose (MTD) established in the first part of the study. Patients will also receive GVHD prophylaxis consisting of a cyclosporine and cellcept starting on day +5 after transplantation.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with MDS/AML 2. 18 years or older and willing and able to comply with the protocol requirements. 3. LVEF ≥ 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated Acquisition Scan (MUGA) is acceptable if ECHO is not available. 4. Patients undergoing 8-10/10 HLA matched unrelated and unmanipulated PBSC transplantation 5. Patients conditioned with reduced intensity or reduced toxicity conditioning of fludarabine with reduced dose (2 days) or myeloabalative doses (4 days) of busulfan or with treosulfan. 6. Patients must sign written informed consent. 7. Adequate birth control in fertile patients.
Exclusion criteria
1. Patients undergoing other type of transplantation or with other type of basic disease other than AML or MDS. 2. Patients with respiratory failure (DLCO \< 30%). 3. Active congestive heart failure (New York Heart Association \[NYHA\] Class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention. 4. Psychiatric conditions/disease that impair the ability to give informed consent or to adequately co-operate 5. Bilirubin \> 3.0 mg/dl, transaminases \> 3 times upper normal limit 6. Creatinine \> 2.0 mg/dl 7. ECOG-Performance status \> 2 8. Uncontrolled infection 9. Pregnancy or lactation 10. CNS disease involvement 11. Pleural effusion or ascites \> 1 liter.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overal survival | 24 months | Overall survival will be calculated from the day of SCT until death or last follow-up. OS will be determined using Kaplan-Meyer product limit method. |
| Disease-free survival | 24 months | Disease-free survival will be calculated from the day of SCT until relapse, death of any cause, or last follow-up. DFS will be determined using Kaplan-Meyer product limit method. |
Countries
Israel
Contacts
Primary ContactArnon Nagler, MD
Backup ContactAvichai Shimoni, MD
Outcome results
None listed