BMT-06: Study of Intensity Modulated Total Marrow Irradiation (IM-TMI)

BMT-06: Phase II Study of Intensity Modulated Total Marrow Irradiation (IM-TMI) in Addition to Fludarabine/Cyclophosphamide and Post-Transplant Cyclophosphamide Conditioning for Partially HLA Mismatched Allogeneic Transplantation in Patients With Acute Leukemia and Myelodysplastic Syndrome (MDS)

This study is being done to see if the addition of a targeted form of radiation to standard conditioning regimen will increase the amount of cancer cells that are killed off in the bone marrow and reduce the chances that your disease may return. This description is called Intensity Modulated Total Marrow Irradiation (IM-TMI).

Study Overview

• Status: Recruiting
• Conditions: Acute Leukemia; MDS
• Intervention / Treatment: Radiation: Conditioning regimen with half-matched (haploidentical) stem cell transplant; Drug: Conditioning regimen with half-matched (haploidentical) stem cell transplant; Drug: Conditioning regimen with half-matched (haploidentical) stem cell transplant; Device: Conditioning regimen with half-matched (haploidentical) stem cell transplant; Other: Conditioning regimen with half-matched (haploidentical) stem cell transplant; Drug: Conditioning regimen with half-matched (haploidentical) stem cell transplant; Drug: Conditioning regimen with half-matched (haploidentical) stem cell transplant; Drug: Conditioning regimen with half-matched (haploidentical) stem cell transplant; Drug: Conditioning regimen with half-matched (haploidentical) stem cell transplant; Drug: Conditioning regimen with half-matched (haploidentical) stem cell transplant

Detailed Description

This is a single arm phase II clinical trial. The usual conditioning regimen for haploidentical transplant is the use of chemotherapy (fludarabine/cyclophosphamide) before the transplant and further chemotherapy with cyclophosphamide after the transplant. In addition, a small dose of radiation is also given.

Patients will receive a standard conditioning regimen with fludarabine, cyclophosphamide and total body irradiation (Flu/Cy/TBI) prior to haploidentical hematopoietic stem cell transplant (HSCT). Graft-versus-host disease prophylaxis will include cyclophosphamide 50 mg/kg on Day +3 and 4 along with tacrolimus and mycophenolate mofetil.

• Study Type: Interventional
• Enrollment (Estimated): 27
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Rondelli Damiano, MD; Phone Number: 312-996-6179; Email: drond@uic.edu
• Study Contact Backup: Name: Marisol Vega, MS; Phone Number: 312-335-5035; Email: vegam35@uic.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • University of Illinois Cancer Center
      • Contact: Rondelli Damiano, MD; Phone Number: 312-996-6179; Email: drond@uic.edu
      • Contact: Marisol Vega, MS; Phone Number: 312-355-5035; Email: vegam35@uic.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Conditioning regimen with half-matched (haploidentical) stem cell transplant

Radiation: Conditioning regimen with half-matched (haploidentical) stem cell transplant; Experimental: Total marrow irradiation 1.5 Gray (Gy) twice a daily on days -3 and -2; Other Names: Total Marrow Irradiation; Drug: Conditioning regimen with half-matched (haploidentical) stem cell transplant; All patients will receive the following standard conditioning regimen: Fludarabine 30 mg/m2 IVPB daily from Day -6 (6 days before stem cell infusion) through Day -2; Other Names: Fludarabine; Drug: Conditioning regimen with half-matched (haploidentical) stem cell transplant; Cyclophosphamide 14.5 mg/kg intravenously prior to transplant on Days -6 and -5; Other Names: Cyclophosphamide; Device: Conditioning regimen with half-matched (haploidentical) stem cell transplant; Total body irradiation 2Gy on Day -1.; Other Names: Total body irradiation; Other: Conditioning regimen with half-matched (haploidentical) stem cell transplant; Stem cell infusion on Day 0.; Other Names: Stem cell transplant; Drug: Conditioning regimen with half-matched (haploidentical) stem cell transplant; Mesna 14.5 mg/kg IV starting 30 minutes prior to cyclophosphamide on Days -6 and -5 and continuing for at least 12 hours after end of cyclophosphamide; Other Names: Mesna; Drug: Conditioning regimen with half-matched (haploidentical) stem cell transplant; Cyclophosphamide 50 mg/kg IV on Days 3 and 4 after transplant at a dose of 50mg/kg per day; Other Names: Cyclophosphamide; Drug: Conditioning regimen with half-matched (haploidentical) stem cell transplant; Mesna 10 mg/kg IV every 4 hours for 10 doses starting 1 hour prior to cyclophosphamide on Days 3 and 4; Other Names: Mesna; Drug: Conditioning regimen with half-matched (haploidentical) stem cell transplant; Tacrolimus 0.03 mg/kg IBW Q24H starting on Day 5; Other Names: Tacrolimus; Drug: Conditioning regimen with half-matched (haploidentical) stem cell transplant; Mycophenolate mofetil (MMF) 15 mg/kg PO TID (maximum daily dose of 3g/day) starting on Day 5; Other Names: Mycophenolate mofetil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of 1 year Graft-Versus-Host Disease (GVHD) free, relapse free survival (GRFS) survival	To evaluate the number of patients with acute leukemia or MDS who are GVHD-free, relapse free (GRFS) after 1 year of undergoing undergoing a treatment regimen of haploidentical stem cell transplant with conditioning and total marrow irradiation.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of patients with greater than or equal to grade 4 non-hematologic toxicities	Evaluate the incidence of greater than or equal to grade 4 non-hematologic toxicities	1 year post-stem cell transplant
Engraftment rates	Engraftment rates at Day 30	30 days post-stem cell transplant
Rates of incidence of full donor chimerism	Rates of incidence of full donor chimerism at Day 30	30 days post-stem cell transplant
The rate of overall survival (OS)	The rate of overall survival (OS)	1 year post-stem cell transplant
The rate of event free-survival (EFS)	The rate of event free-survival (EFS)	1 year post-stem cell transplant
The rate of Grade II-IV and III-IV acute GVHD and limited/extensive chronic GVHD	The rate of Grade II-IV and III-IV acute GVHD and limited/extensive chronic GVHD	1 year post-stem cell transplant
The rate of progression at 1 year post transplant	The rate of progression at 1 year post transplant	1 year post-stem cell transplant
The rate of relapse at 1 year post transplant	The rate of relapse at 1 year post transplant	1 year post-stem cell transplant
The rate of non-morality (NRM) at 1 year post transplant	The rate of non-morality (NRM) at 1 year post transplant	1 year post-stem cell transplant

Collaborators and Investigators

• Sponsor: University of Illinois at Chicago
• Investigators: Principal Investigator: Rondelli Damiano, MD, University of Illinois at Chicago

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2020
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: November 11, 2019
• First Submitted That Met QC Criteria: December 3, 2019
• First Posted (Actual): December 5, 2019

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Stem Cell Transplant; Half-matched (haploidentical) stem cell transplant
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia; Sulfur Compounds; Organic Chemicals; Investigative Techniques; Therapeutics; Fatty Acids; Lipids; Surgical Procedures, Operative; Hydrocarbons, Acyclic; Hydrocarbons; Acids, Acyclic; Carboxylic Acids; Transplantation; Alkanes; Alkanesulfonates; Alkanesulfonic Acids; Sulfonic Acids; Sulfur Acids; Macrolides; Lactones; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Radiotherapy; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Immunologic Techniques; Caproates; Sulfhydryl Compounds; Immunomodulation; Immunotherapy; Immunosuppression Therapy; Cyclophosphamide; Mycophenolic Acid; Tacrolimus; Mesna; fludarabine; Stem Cell Transplantation; Whole-Body Irradiation; Transplantation Conditioning
• Other Study ID Numbers: 2019-1149

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes