Acute Leukemia, Acute Myeloid Leukemia, AML, MDS, Myelodysplastic Syndromes
Conditions
Brief summary
This is a Phase II study following subjects proceeding with Treosulfan (36g/m2) preparative regimen followed by a related, unrelated, or partially matched family donor stem cell infusion, with post-transplant cyclophosphamide (PTCy) at 40mg/kg, tacrolimus and MMF for GVHD prophylaxis.
Interventions
DRUGTreosulfan
12 g/m2 administered intravenously over 2 hours on days -4, -3, and -2.
DRUGFludarabine
Fludarabine will be administered intravenously over 1 hour, every 24 hours on days -6 to -2. The daily dose of fludarabine will be determined by model-based dosing utilizing Bayesian methodology .
RADIATIONTotal Body Irradiation
TBI 200 cGy will be administered as a single treatment on day -1 per current institutional guidelines.
DRUGTacrolimus
Tacrolimus may be initiated on day +5 either PO or IV gtt , with a goal trough level of 5-10mg/mL and avoiding higher levels for the first two weeks post-transplant, as recent evidence demonstrated increased adverse events for levels over 10 mg/mL.
DRUGMycophenolate Mofetil
All patients begin mycophenolate mofetil (MMF) day +5 through day +35 if no acute GVHD or 7 days after engraftment, whichever is later.
DRUGCyclophosphamid
Cyclophosphamide 40 mg/kg will be given as an IV infusion over 1-2 hours (depending on volume) on Days +3 post-transplant (between 60 and 72 hours after stem cell infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide).
BIOLOGICALStem Cell Infusion
Given on day 0.
Sponsors
Masonic Cancer Center, University of Minnesota
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients 2-75 years of age * ≤7 5 years of age: Karnofsky score ≥ 70% (≥ 16 years) or Lansky play score ≥ 50 (\< 16 years) with appropriate organ criteria as below (in other inclusion criteria) * 5/6 or 6/6 related donor, OR a 5-8/8 HLA-A, B, C, DRB1 allele match unrelated donor, OR a haplotype (at least 5/10) related donor * adequate liver (no decompensated liver failure, Child Pugh A, AST/ALT \<5X ULN) and renal function (creatinine \<2.0) * absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction ≥ 40% * DLCO FEV1, FVC ≥ 40% predicted, and absence of O2 requirement
Exclusion criteria
* Pregnant or breastfeeding * Evidence of untreated/uncontrolled HIV infection * Untreated active serious infection * Active CNS malignancy * CML in blast crisis not in a complete remission by abnormal blast count. * Less than 3 months since prior myeloablative transplant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Day 100 | Evaluate rates of overall survival at 100 days after transplant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Transplant Related Mortality | Day 100 and 1 year | ● Estimate transplant related mortality (TRM) at 100 days and 1 year with this conditioning and GVHD prophylaxis combination |
| Overall Survival | 1 and 2 years | Estimate overall survival at 1 and 2 years |
Countries
United States
Contacts
CONTACTChristopher Graham, MD
Outcome results
None listed