Clinical Trials /

QUILT-3.034: Non-Myeloablative TCRa/b Deplete Haplo HSCT With Post ALT-803 for AML

NCT03365661

Description:

This is a phase II multi-institutional therapeutic study of a non-myeloablative T cell receptor (TCR) alpha/beta depleted haploidentical transplantation with post-transplant immune reconstitution using ALT-803 for the treatment of high-risk myeloid leukemia (AML), treatment-related/secondary AML, and myelodysplastic syndrome (MDS).

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

Withdrawn

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: QUILT-3.034: Non-Myeloablative TCRa/b Deplete Haplo HSCT With Post ALT-803 for AML
  • Official Title: QUILT-3.034: Multi-Center Trial of Non-Myeloablative TCRa/b Deplete Haploidentical Hematopoietic Cell Transplantation With Post HCT ALT-803 in High-Risk Myeloid Diseases

Clinical Trial IDs

  • ORG STUDY ID: 2016LS057
  • SECONDARY ID: MT2016-06
  • NCT ID: NCT03365661

Conditions

  • High-Risk Acute Myeloid Leukemia
  • Treatment-Related Acute Myeloid Leukemia
  • Secondary Acute Myeloid Leukemia
  • Myelodysplastic Syndrome

Interventions

DrugSynonymsArms
ALT-803ALT-803

Purpose

This is a phase II multi-institutional therapeutic study of a non-myeloablative T cell receptor (TCR) alpha/beta depleted haploidentical transplantation with post-transplant immune reconstitution using ALT-803 for the treatment of high-risk myeloid leukemia (AML), treatment-related/secondary AML, and myelodysplastic syndrome (MDS).

Trial Arms

NameTypeDescriptionInterventions
ALT-803Experimental

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Age ≥18 to ≤70 years
    
              -  Meets one of the following disease and risk categories:
    
                   -  High-Risk Acute Myeloid Leukemia (AML) with predicted risk of relapse higher than
                      30%, which includes, but not limited to the following:
    
                        -  Patients in morphological remission (CR1 or beyond) with minimal residual
                           disease as quantified either by flow cytometry, or by cytogenetics or
                           molecular markers.
    
                        -  Patients with the following karyotypes in morphological CR or CRi:
                           ELN-Intermediate I, Adverse, ELN-Intermediate-II. (18) (Examples include
                           monosomal karyotype, complex karyotype, mutant p53, mutant RUNX1, mutant
                           ASXL1, mutant FLT3-ITD, mutant DNMT3A, Inversion 3, T(6:9), KIT mutated core
                           binding factor AML)
    
                   -  Treatment-Related AML and Secondary AML in morphological remission (CR1 or
                      beyond) with minimal residual disease as quantified either by flow cytometry, or
                      by cytogenetics or molecular markers
    
                   -  Myelodysplastic Syndrome (MDS) with < 5% blasts by morphology and meets at least
                      one of the following:
    
                        -  Received intensive induction chemotherapy (i.e. 7+3 or MEC) OR
    
                        -  Progression after 4 cycles of hypomethylating agents
    
                   -  The donor and recipient must be HLA identical for at least one haplotype (using
                      high resolution DNA based typing) at the following genetic loci: HLA-A, HLA-B,
                      HLA-C, and HLA-DRB1
    
              -  Karnofsky performance status ≥ 60% (appendix IV)
    
              -  Adequate organ function within 14 days of study registration (30 days for pulmonary
                 and cardiac) defined as:
    
                   -  Hepatic: AST and ALT < 3 x upper limit of institutional normal
    
                   -  Renal: estimated glomerular filtration rate (GFR) ≥ 40 mL/min/1.73m2
    
                   -  Pulmonary: oxygen saturation ≥ 90% on room air with no symptomatic pulmonary
                      disease. If symptomatic or prior known impairment DLCOcor ≥ 40%.
    
                   -  Cardiac: LVEF ≥ 40% by echocardiography, MUGA, or cardiac MRI, no uncontrolled
                      angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic
                      evidence of acute ischemia or active conduction system abnormalities
    
              -  Able to be off prednisone or other immunosuppressive medications for at least 3 days
                 prior to transplant (excluding preparative regimen pre-medications)
    
              -  Sexually active females of child bearing potential and males with partners of child
                 bearing potential must agree to use effective contraception during therapy and for 4
                 months after completion of therapy
    
              -  Voluntary written consent prior to the performance of any research related procedures
    
            Exclusion Criteria:
    
              -  Acute leukemias of ambiguous lineage
    
              -  Allogeneic transplant for AML within the previous 6 months (no time limit for
                 autologous transplant)
    
              -  Active CNS disease - if a history of AML related CNS involvement, screening CSF
                 analysis must be negative
    
              -  Pregnant or breastfeeding - The agents used in this study include those that fall
                 under Pregnancy Category D - have known teratogenic potential. Women of child bearing
                 potential must have a negative pregnancy test at screening
    
              -  Active autoimmune disease requiring systemic immunosuppressive therapy
    
              -  History of severe asthma and currently on systemic chronic medications (mild asthma
                 requiring inhaled steroids only is eligible)
    
              -  New or progressive pulmonary infiltrates on screening chest x-ray or chest CT scan
                 unless cleared for study by Pulmonary. Infiltrates attributed to infection must be
                 stable/improving (with associated clinical improvement) after 1 week of appropriate
                 therapy (4 weeks for presumed or documented fungal infections).
    
              -  Uncontrolled bacterial, fungal or viral infections including HIV-1/2 or active
                 hepatitis C/B - chronic asymptomatic viral hepatitis is allowed
    
              -  Active concomitant second malignancy (i.e. has required treatment in the previous 6
                 months)
    
              -  Known hypersensitivity to any of the study agents
    
              -  Received any investigational drugs within the 14 days before 1st dose of fludarabine
          
    Maximum Eligible Age:70 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Incidence of disease response
    Time Frame:Day 28
    Safety Issue:
    Description:Rate of donor neutrophil engraftment in the absence of disease at Day +28. Neutrophil engraftment is defined as absolute neutrophil count (ANC) ≥ 5 X 10 8 /L.

    Secondary Outcome Measures

    Measure:Disease Free Survival (DFS)
    Time Frame:12 months
    Safety Issue:
    Description:Incidence of disease free survival (DFS).
    Measure:Treatment Related Mortality (TRM)
    Time Frame:12 months
    Safety Issue:
    Description:Incidence of treatment related mortality (TRM).
    Measure:Disease Relapse
    Time Frame:12 months
    Safety Issue:
    Description:Incidence of disease relapse.
    Measure:Grade II-IV acute Graft versus Host Disease (aGVHD)
    Time Frame:Day 100
    Safety Issue:
    Description:Incidence of acute Graft versus Host Disease measured by the number of T-cells infused or NK cells engrafted causing GVHD syndrome.
    Measure:Serious Adverse Events from ALT-803 (Early Schedule)
    Time Frame:1 Year
    Safety Issue:
    Description:Incidence of serious adverse events from ALT-803 will be measured for an initial 2 doses, given one week apart.
    Measure:Serious Adverse Events from ALT-803 (Late Schedule)
    Time Frame:1 Year
    Safety Issue:
    Description:Incidence of serious adverse events from ALT-803 will be measured for 16 doses, given over 4 weeks.
    Measure:Chronic Graft versus Host Disease (cGVHD)
    Time Frame:1 year
    Safety Issue:
    Description:Incidence of chronic Graft versus Host Disease will be measured by the number of T-cells infused or NK cells engrafted causing GVHD syndrome.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Masonic Cancer Center, University of Minnesota

    Trial Keywords

    • AML
    • MDS

    Last Updated