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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03365661
Recruitment Status : Withdrawn (Sponsor halted study.)
First Posted : December 7, 2017
Last Update Posted : November 9, 2018
Sponsor:
Collaborator:
University of Minnesota
Information provided by (Responsible Party):
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).

Condition or disease Intervention/treatment Phase
High-Risk Acute Myeloid Leukemia Treatment-Related Acute Myeloid Leukemia Secondary Acute Myeloid Leukemia Myelodysplastic Syndrome Biological: ALT-803 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : October 30, 2018
Estimated Primary Completion Date : January 1, 2023
Estimated Study Completion Date : January 1, 2023


Arm Intervention/treatment
Experimental: ALT-803 Biological: ALT-803
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.




Primary Outcome Measures :
  1. Incidence of disease response [ Time Frame: 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 :
  1. Disease Free Survival (DFS) [ Time Frame: 12 months ]
    Incidence of disease free survival (DFS).

  2. Treatment Related Mortality (TRM) [ Time Frame: 12 months ]
    Incidence of treatment related mortality (TRM).

  3. Disease Relapse [ Time Frame: 12 months ]
    Incidence of disease relapse.

  4. Grade II-IV acute Graft versus Host Disease (aGVHD) [ Time Frame: Day 100 ]
    Incidence of acute Graft versus Host Disease measured by the number of T-cells infused or NK cells engrafted causing GVHD syndrome.

  5. Serious Adverse Events from ALT-803 (Early Schedule) [ Time Frame: 1 Year ]
    Incidence of serious adverse events from ALT-803 will be measured for an initial 2 doses, given one week apart.

  6. Serious Adverse Events from ALT-803 (Late Schedule) [ Time Frame: 1 Year ]
    Incidence of serious adverse events from ALT-803 will be measured for 16 doses, given over 4 weeks.

  7. Chronic Graft versus Host Disease (cGVHD) [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03365661


Locations
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United States, Minnesota
Masonic Cancer Center
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
University of Minnesota
Investigators
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Principal Investigator: Sarah Cooley, MD University of Minnesota
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Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT03365661    
Other Study ID Numbers: 2016LS057
MT2016-06 ( Other Identifier: Masonic Cancer Center, University of Minnesota )
First Posted: December 7, 2017    Key Record Dates
Last Update Posted: November 9, 2018
Last Verified: November 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Masonic Cancer Center, University of Minnesota:
AML
MDS
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases