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

NCT03365661 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 2016LS057MT2016-06
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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).

Conditions

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

Keywords

AML; MDS

Outcome Measures

Primary Outcomes (1)

• Incidence of disease response

  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.

  Day 28

Secondary Outcomes (7)

• Disease Free Survival (DFS)

  12 months

• Treatment Related Mortality (TRM)

  12 months

• Disease Relapse

  12 months

• Grade II-IV acute Graft versus Host Disease (aGVHD)

  Day 100

• Serious Adverse Events from ALT-803 (Early Schedule)

  1 Year

Study Arms (1)

ALT-803

EXPERIMENTAL

Biological: ALT-803

Interventions

ALT-803 BIOLOGICAL

A reduced intensity conditioning starts on Day -6, (CY/FLU/TBI/TLI) followed by infusion of a TCRα/β-deplete haploidentical graft on Day 0. Two doses of ALT-803 are given initially (early) 1 week apart to facilitate NK cell expansion. ALT-803 maintenance (late) for immune reconstitution begins at Day 42 and consists of 4 weekly doses, followed by 4 weeks off. Up to four 8 week treatment courses are permitted. No post-transplant GVHD prophylaxis is administered unless the final donor cell product contains \> 2 x 105 α/β T cells/kg recipient weight.

ALT-803

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%.

You may not qualify if:

• 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

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead
• University of Minnesota: collaborator

Study Sites (1)

Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

ALT-803

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Sarah Cooley, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2017
• First Posted: December 7, 2017
• Study Start: October 30, 2018
• Primary Completion: January 1, 2023
• Study Completion: January 1, 2023
• Last Updated: November 9, 2018

Record last verified: 2018-11

Locations

US (1)