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

NCT ID: NCT04187105

Last Updated: 2024-12-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

27 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-01-27

Study Completion Date

2026-12-31

Brief Summary

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Pre-transplant conditioning will include targeted total marrow irradiation (TMI) at a dose of 6Gy. Graft-versus-host disease prophylaxis will include cyclophosphamide 50 mg/kg on Day +3 and 4 along with tacrolimus and mycophenolate mofetil

Detailed Description

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This is a single arm phase II clinical trial. 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). In addition the pre-transplant conditioning will include targeted total marrow irradiation (TMI) at a dose of 6Gy. Graft-versus-host disease prophylaxis will include cyclophosphamide 50 mg/kg on Day +3 and 4 along with tacrolimus and mycophenolate mofetil.

Conditions

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Acute Leukemia MDS

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Single group assignment to Arm 1
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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Arm1

Experimental: Total marrow irradiation 1.5 Gray (Gy) twice a daily on days -3 and -2

Intervention Type DEVICE

Arm1

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

Intervention Type DRUG

Arm1

IV cyclophosphamide 14.5 mg/kg intravenously prior to transplant on Days -6 and -5.

Intervention Type DRUG

Arm 1

Total body irradiation 2Gy on day -1.

Intervention Type DEVICE

Arm1

Stem cell infusion on day 0.

Intervention Type OTHER

Arm1

Tacrolimus IV initially in doses of 0.15 mg/kg/day for 3 days, followed by conversion to oral therapy (0.15 mg/kg twice daily)

Intervention Type DRUG

Arm1

Cyclophosphamide on days 3 and 4 after transplant at a dose of 50mg/kg per day

Intervention Type DRUG

Other Intervention Names

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Fludarabine Cyclophosphamide Total body irradiation Stem cell transplant Tacrolimus Cyclophosphamide

Eligibility Criteria

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Inclusion Criteria

1. Patient age 18-75 years
2. Related donor who is, at minimum, Human Leukocyte Antigen (HLA) haploidentical. The donor and recipient must be identical 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 5/10 is therefore required, and will be considered sufficient evidence that the donor and recipient share one HLA haplotype. In addition, unrelated donors who are mismatched at least one of the following loci: HLA-A, HLA-B, HLA-Cw, HLA-or DRB1.
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 e. Mixed lineage and biphenotypic leukemia
4. Adequate end-organ function as measured by:

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

Exclusion Criteria

1. Presence of significant co morbidity as shown by:

1. Left ventricular ejection fraction \< 40%
2. Bilirubin \> 2.0 mg/dL (unless due to Gilbert's syndrome or hemolysis), and ALT and AST \> 5 x ULN
3. FEV1 and FVC \< 50% of predicted or DLCO \<50% of predicted once corrected for anemia
4. Karnofsky score \<70
5. 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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Illinois at Chicago

OTHER

Sponsor Role lead

Responsible Party

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Damiano Rondelli, MD

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Rondelli Damiano, MD

Role: PRINCIPAL_INVESTIGATOR

University of Illinois at Chicago

Locations

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University of Illinois Cancer Center

Chicago, Illinois, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Rondelli Damiano, MD

Role: CONTACT

Phone: 312-996-6179

Email: [email protected]

Marisol Vega, MS

Role: CONTACT

Phone: 312-335-5035

Email: [email protected]

Facility Contacts

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Rondelli Damiano, MD

Role: primary

Marisol Vega, MS

Role: backup

Other Identifiers

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2019-1149

Identifier Type: -

Identifier Source: org_study_id