Intensity Modulated Total Marrow Irradiation for Acute Leukemia and MDS

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This clinical trial evaluates the effectiveness of intensity-modulated total marrow irradiation (IM-TMI) as part of the pre-transplant conditioning regimen for patients with acute leukemia or myelodysplastic syndromes (MDS). Participants will receive a combination of fludarabine, cyclophosphamide, and total body irradiation, along with targeted TMI at a dose of 6Gy. The study aims to improve outcomes by using a haploidentical hematopoietic stem cell transplant (HSCT) approach, with specific graft-versus-host disease prophylaxis measures in place. It is a single-arm phase II trial, focusing on a defined patient population with specific genetic matching criteria for donors.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. Patient age 18-75 years
2. Related donor who is, at minimum, Human Leukocyte Antigen (HLA) haploidentical or mismatched unrelated donor.

   * Haploidentical: The donor and recipient must be identical in at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1. A minimum match of 4/8 if using HLA-A,-B,-DRB1,-Cw, or 5/10 if using HLA-A,-B,-Cw ,-DRB1, and -DQB1, will be considered evidence that the donor and recipient share one HLA haplotype.
   * Unrelated donors: unrelated donors who are mismatched in one or more of the following loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1,HLA-DQB1- can be included with a maximum of 4/8 or 5/10 mismatches.
3. Eligible diagnoses are listed below. Patient must have one of the following:

   1. Relapsed or refractory acute leukemia (including AML or ALL in CR2 and primary refractory leukemia).
   2. Poor-risk AML in first remission:

      * AML arising from MDS or a myeloproliferative disorder, or secondary AML
      * Poor risk molecular features including but not limited to presence of FLT3 internal tandem duplication mutation.
      * Poor-risk cytogenetics: Monosomal karyotype, complex karyotype (\> 3 abnormalities), inv(3), t(3;3), t(6;9), MLL rearrangement with the exception of t(9;11), or abnormalities of chromosome 5 or 7
   3. Poor risk ALL in first remission:

      * Poor risk cytogenetics: Philadelphia Chromosome, t(4;11), KMT2A translocation, t(8;14), complex karyotype (⩾ 5 chromosomal abnormalities) and low hypodiploidy (30-39 chromosomes)/near triploidy (60-78 chromosomes)
      * Philadelphia-like ALL
      * Presentation WBC \>30 × 109 for B-ALL or \>100 109 for T-ALL
      * Age\>35
      * Poor MRD clearance, defined as levels \>1 × 10-3 after induction and levels \>5 × 10-4 after early consolidation by flow cytometry
   4. Myelodysplastic syndromes (MDS) with at least one of the following poor-risk features:

      * i. Poor-risk cytogenetics (including but not limited to 7/7q minus or complex cytogenetics)
      * ii. IPSS score of INT-2 or greater
      * iii. Treatment-related or Secondary MDS
      * iv. MDS diagnosed before age 21 years
      * v. Progression on or lack of response to standard DNA-methyltransferase inhibitor therapy
      * vi. Life-threatening cytopenias, including those generally requiring greater than weekly transfusions
      * vii. Poor risk molecular features including but not limited to the presence of BCOR, ASXL1, p53 or RUNX1 mutations
   5. Mixed lineage and biphenotypic leukemia
4. Adequate end-organ function as measured by:

   * a. Left ventricular ejection fraction ≥ 40%
   * b. Bilirubin ≤ 2.0 mg/dL (unless due to Gilbert's syndrome or hemolysis), and ALT and AST \< 5 x ULN
   * c. FEV1 and FVC \> 50% of predicted

Exclusion Criteria:

1. Presence of significant co morbidity as shown by:

   * a. Left ventricular ejection fraction \< 40%
   * b. Bilirubin \> 2.0 mg/dL (unless due to Gilbert's syndrome or hemolysis), and ALT and AST \> 5 x ULN
   * c. FEV1 and FVC \< 50% of predicted or DLCO \<50% of predicted once corrected for anemia
   * d. Karnofsky score \<70
   * e. History of cirrhosis
2. Patients unable to sign informed consent
3. Patient who have previously received radiation to \>20% of bone marrow containing areas (assessed by radiation oncology physician)

Where it's running

• University of Illinois Cancer Center
  Chicago, Illinois, United States Recruiting

Study contacts

• Principal investigator: Rondelli Damiano, MD — University of Illinois Chicago
• Study coordinator: Rondelli Damiano, MD
• Email: drond@uic.edu
• Phone: 312-996-6179

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.