Clinical Trials /

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

NCT04187105

Description:

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

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 2019-1149
  • NCT ID: NCT04187105

Conditions

  • Acute Leukemia
  • MDS

Interventions

DrugSynonymsArms
Arm1Fludarabine
Arm1Cyclophosphamide
Arm1Tacrolimus
Arm1Cyclophosphamide

Purpose

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

      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.
    

Trial Arms

NameTypeDescriptionInterventions

Eligibility Criteria

        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)
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of 1 year Graft-Versus-Host Disease (GVHD) free
Time Frame:1 year
Safety Issue:
Description:To evaluate the number of patients with acute leukemia or MDS that are GVHD free

Secondary Outcome Measures

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Illinois at Chicago

Last Updated

December 3, 2019