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)

Plain English Summary

BMT-06: Study of Intensity Modulated Total Marrow Irradiation (IM-TMI) is a Phase 2 clinical trial sponsored by University of Illinois at Chicago studying Acute Leukemia, MDS. This trial tests a new radiation method called Intensity Modulated Total Marrow Irradiation (IM-TMI) combined with standard chemotherapy and stem cell transplant. It is for adults (18-75 years) with specific types of acute leukemia or myelodysplastic syndromes (MDS) who need a stem cell transplant from a partially matched donor. Participation involves receiving the new radiation technique along with standard treatments before a stem cell transplant. Standard treatment for these conditions typically involves chemotherapy and a stem cell transplant, but this trial explores adding a targeted radiation approach. The trial aims to enroll 27 participants.

Official Summary

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).

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are between 18 and 75 years old and have been diagnosed with certain types of acute leukemia or MDS. You must have a stem cell donor who is a close family member (haploidentical) or an unrelated donor with some genetic differences. Your leukemia or MDS should be relapsed, refractory, or considered high-risk even in first remission. You need to have adequate organ function, including heart, liver, and lung function, and a good performance status. This trial is studying Acute Leukemia, MDS, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The main goal is to see if patients are alive and free from their disease and graft-versus-host disease (a complication of transplant) one year after the transplant. The specific primary outcome measures are: Rate of 1 year Graft-Versus-Host Disease (GVHD) free, relapse free survival (GRFS) survival (1 year). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial aims to improve outcomes for patients with high-risk leukemia and MDS by using a more targeted radiation therapy to kill cancer cells before a stem cell transplant, potentially reducing dis Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Acute Leukemia, MDS, where improved treatment options are needed.

Investor Insight

This trial addresses a critical need for improved outcomes in high-risk blood cancers, potentially expanding the use of stem cell transplants with partially matched donors and representing a significa Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific risks and benefits of IM-TMI compared to standard radiation or no radiation. Understand the full schedule of treatments, including chemotherapy, radiation, and the stem cell transplant process. Be prepared for potential side effects and the need for close monitoring during and after the transplant. This trial is currently recruiting participants. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 27 participants

Interventions

• 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
• 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
• DRUG: Conditioning regimen with half-matched (haploidentical) stem cell transplant — Cyclophosphamide 14.5 mg/kg intravenously prior to transplant on Days -6 and -5
• DEVICE: Conditioning regimen with half-matched (haploidentical) stem cell transplant — Total body irradiation 2Gy on Day -1.
• OTHER: Conditioning regimen with half-matched (haploidentical) stem cell transplant — Stem cell infusion on Day 0.

Primary Outcomes

• Rate of 1 year Graft-Versus-Host Disease (GVHD) free, relapse free survival (GRFS) survival (1 year)

Secondary Outcomes

• The number of patients with greater than or equal to grade 4 non-hematologic toxicities (1 year post-stem cell transplant)
• Engraftment rates (30 days post-stem cell transplant)
• Rates of incidence of full donor chimerism (30 days post-stem cell transplant)
• The rate of overall survival (OS) (1 year post-stem cell transplant)
• The rate of event free-survival (EFS) (1 year post-stem cell transplant)

Full Eligibility Criteria

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)

Trial Locations

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

Frequently Asked Questions

Related Conditions

• Acute Myeloid Leukemia (AML)
• Acute Lymphoblastic Leukemia (ALL)
• Myelodysplastic Syndromes (MDS)
• Hematopoietic Stem Cell Transplantation
• Bone Marrow Transplantation
• Leukemia
• Blood Cancers
• Graft-versus-Host Disease (GVHD)
• Refractory Leukemia
• Relapsed Leukemia

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