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

University of Minnesota (UMN)

Status and phase

Withdrawn

Phase 2

Conditions

Secondary Acute Myeloid Leukemia

Treatment-Related Acute Myeloid Leukemia

High-Risk Acute Myeloid Leukemia

Myelodysplastic Syndrome

Treatments

Biological: ALT-803

Study type

Interventional

Funder types

Other

Identifiers

NCT03365661

2016LS057

MT2016-06 (Other Identifier)

Details and patient eligibility

About

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).

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

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