MT2025-35 Allogeneic Hematopoietic Stem Cell Transplantation Using Reduced Intensity Conditioning Treosulfan and Fludarabine, With Post-Transplant Cytoxan (PTCy) for the Treatment of Hematological Diseases

Purpose

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.

Conditions

  • AML
  • MDS
  • Acute Leukemia
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes

Eligibility

Eligible Ages
Between 2 Years and 75 Years
Eligible Sex
All
Accepts 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

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Treo/Flu with PTCy 		Subjects treated with Treosulfan and Fludarabine preparative regimen with TBI for AML and MDS patients followed by a related or unrelated donor stem cell infusion utilizing PTCy, tacrolimus and MMF as GVHD prophylaxis.
  • Drug: Treosulfan
    12 g/m2 administered intravenously over 2 hours on days -4, -3, and -2.
  • Drug: Fludarabine
    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 .
  • Radiation: Total Body Irradiation
    TBI 200 cGy will be administered as a single treatment on day -1 per current institutional guidelines.
    Other names:
    • TBI
  • Drug: Tacrolimus
    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.
  • Drug: Mycophenolate Mofetil
    All patients begin mycophenolate mofetil (MMF) day +5 through day +35 if no acute GVHD or 7 days after engraftment, whichever is later.
    Other names:
    • MMF
  • Drug: Cyclophosphamid
    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).
  • Biological: Stem Cell Infusion
    Given on day 0.

Recruiting Locations

Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota 55455

More Details

Status
Recruiting
Sponsor
Masonic Cancer Center, University of Minnesota

Study Contact

Christopher Graham, MD
612-625-3051
grah0329@umn.edu