QUILT-3.034: Non-Myeloablative TCRa/b Deplete Haplo HSCT With Post ALT-803 for AML
- Conditions
- High-Risk Acute Myeloid LeukemiaSecondary Acute Myeloid LeukemiaTreatment-Related Acute Myeloid LeukemiaMyelodysplastic Syndrome
- Registration Number
- NCT03365661
- Lead Sponsor
- Masonic Cancer Center, University of Minnesota
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
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Age ≥18 to ≤70 years
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Meets one of the following disease and risk categories:
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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)
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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
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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
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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
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Karnofsky performance status ≥ 60% (appendix IV)
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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
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Able to be off prednisone or other immunosuppressive medications for at least 3 days prior to transplant (excluding preparative regimen pre-medications)
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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
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Voluntary written consent prior to the performance of any research related procedures
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method Incidence of disease response Day 28 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
Name Time Method Disease Free Survival (DFS) 12 months Incidence of disease free survival (DFS).
Treatment Related Mortality (TRM) 12 months Incidence of treatment related mortality (TRM).
Grade II-IV acute Graft versus Host Disease (aGVHD) Day 100 Incidence of acute Graft versus Host Disease measured by the number of T-cells infused or NK cells engrafted causing GVHD syndrome.
Serious Adverse Events from ALT-803 (Early Schedule) 1 Year Incidence of serious adverse events from ALT-803 will be measured for an initial 2 doses, given one week apart.
Serious Adverse Events from ALT-803 (Late Schedule) 1 Year Incidence of serious adverse events from ALT-803 will be measured for 16 doses, given over 4 weeks.
Chronic Graft versus Host Disease (cGVHD) 1 year Incidence of chronic Graft versus Host Disease will be measured by the number of T-cells infused or NK cells engrafted causing GVHD syndrome.
Disease Relapse 12 months Incidence of disease relapse.
Trial Locations
- Locations (1)
Masonic Cancer Center
🇺🇸Minneapolis, Minnesota, United States
Masonic Cancer Center🇺🇸Minneapolis, Minnesota, United States