Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

QUILT-3.033: Haplo NK With SQ ALT-803 for Adults With Relapsed or Refractory 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: NCT03050216
Recruitment Status : Suspended (Interim Analysis)
First Posted : February 10, 2017
Last Update Posted : February 15, 2019
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Tracking Information
First Submitted Date  ICMJE February 8, 2017
First Posted Date  ICMJE February 10, 2017
Last Update Posted Date February 15, 2019
Actual Study Start Date  ICMJE May 16, 2017
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 31, 2017)
Rate of complete remission with or without incomplete platelet recovery [ Time Frame: Day 42 post NK cell infusion ]
To estimate the rate of complete remission with incomplete platelet recovery (CRp) - defined as leukemic clearance and neutrophil recovery without platelet recovery - by day 42 after the infusion of CD3/CD19 depleted, ALT-803 stimulated, donor NK cells and subcutaneous ALT-803 given after a non-myeloablative preparative regimen for the treatment of refractory or released acute myelogenous leukemia (AML)
Original Primary Outcome Measures  ICMJE
 (submitted: February 8, 2017)
Rate of complete remission with incomplete platelet recovery [ Time Frame: Day 42 post NK cell infusion ]
To estimate the rate of complete remission with incomplete platelet recovery (CRp) - defined as leukemic clearance and neutrophil recovery without platelet recovery - by day 42 after the infusion of CD3/CD19 depleted, ALT-803 stimulated, donor NK cells and subcutaneous ALT-803 given after a non-myeloablative preparative regimen for the treatment of refractory or released acute myelogenous leukemia (AML)
Change History Complete list of historical versions of study NCT03050216 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 31, 2017)
  • Incidence of in vivo expansion ≥100 of donor derived NK cells per uL blood [ Time Frame: Day 14 post NK cell infusion ]
  • ALT-803 associated toxicity assessment [ Time Frame: Day 0 ]
    Toxicity will be classified and graded according to NCI's Common Terminology Criteria for Adverse Events V 4.0 (CTCAE)
  • ALT-803 associated toxicity assessment [ Time Frame: Day 5 ]
    Toxicity will be classified and graded according to NCI's Common Terminology Criteria for Adverse Events V 4.0 (CTCAE)
  • ALT-803 associated toxicity assessment [ Time Frame: Day 7 ]
    Toxicity will be classified and graded according to NCI's Common Terminology Criteria for Adverse Events V 4.0 (CTCAE)
  • ALT-803 associated toxicity assessment [ Time Frame: Day 10 ]
    Toxicity will be classified and graded according to NCI's Common Terminology Criteria for Adverse Events V 4.0 (CTCAE)
  • Treatment related mortality [ Time Frame: 6 months post-therapy ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 8, 2017)
  • Incidence of in vivo expansion ≥100 of donor derived NK cells per uL blood [ Time Frame: Day 14 post NK cell infusion ]
  • ALT-803 associated toxicity assessment [ Time Frame: Days 0, 5, 10 ]
    Toxicity will be classified and graded according to NCI's Common Terminology Criteria for Adverse Events V 4.0 (CTCAE)
  • Treatment related mortality [ Time Frame: 6 months post-therapy ]
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE QUILT-3.033: Haplo NK With SQ ALT-803 for Adults With Relapsed or Refractory AML
Official Title  ICMJE QUILT-3.033: Haploidentical Donor Natural Killer (NK) Cell Infusion With Subcutaneous ALT-803 in Adults With Refractory or Relapsed Acute Myelogenous Leukemia
Brief Summary This is a multi-institutional Simon's optimal two-stage phase II trial of CD3/CD19 depleted, ALT-803 activated, haploidentical donor NK cells and subcutaneous ALT-803 given after lymphodepleting chemotherapy (CY/FLU) for the treatment of refractory or released acute myelogenous leukemia (AML).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Myeloid Leukemia
Intervention  ICMJE Biological: ALT-803

Preparative Regimen:

Fludarabine 25 mg/m2 x 5 days start day -6 Cyclophosphamide 60 mg/kg x 2 days on day -5 and -4

ALT-803 Stimulated Donor NK Cells:

The apheresis product (collected day -1) will be enriched for NK cells with the large-scale CliniMacs® device (Miltenyi) by depletion of CD3+ cells to remove T-lymphocytes and depletion of CD19+ cells to remove B-lymphocytes. The NK cell enriched product will be stimulated by overnight incubation with 36.1 ng/mL ALT-803 under GMP conditions and infused on day 0.

ALT-803 to Facilitate NK Cell Survival and Expansion:

ALT-803 at 10 mcg/kg subcutaneously (SC) with the 1st dose administered on day 0 (no sooner than 4 hours post NK cells), day +5 and day +10 for 3 doses total

Study Arms Experimental: Cy, FLU, Haplo NK and ALT-803

Preparative Regimen of Fludarabine and Cyclophosphamide

ALT-803 Activation of Donor NK Cells

ALT-803 to Facilitate NK Cell Survival and Expansion

Intervention: Biological: ALT-803
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Suspended
Estimated Enrollment  ICMJE
 (submitted: February 8, 2017)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date September 2020
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of acute myeloid leukemia (AML) and meets one of the following disease criteria:

    • Primary induction failure:

      • De novo AML - no CR after 2 or more chemotherapy induction attempts
      • Secondary AML (from MDS or treatment related): no CR after 1 or more chemotherapy induction attempts
    • Relapse after chemotherapy: not in CR after 1, 2, or 3 re-induction attempts

      *** Patients > 60 years of age, the 1 cycle of chemotherapy is not required

    • Relapse after hematopoietic stem cell transplant:

      • Relapse must have occurred > 18 months after transplant
      • No re-induction required and no more than 1 re-induction attempt is allowed.
  • Notes:

    1. For hypomethylating agents (i.e. decitabine, azacititdine) to count as an induction/re-induction attempt, the patient must have completed a minimum of 3 monthly cycles
    2. For targeting agents (i.e. sorafenib) to count as an induction/re-induction attempt, the patient must have completed a minimum of 1 month without attaining CR
    3. 7+3 followed by 5+2 counts as TWO induction attempts
    4. Use of hydroxyurea is permitted to control blasts until Day -3 per Section 8.7
    5. A history of AML related CNS involvement is allowed if CSF analysis is negative on 2 test dates at least 2 weeks apart prior to study treatment. The use of ongoing CNS maintenance therapy is allowed while on study.
  • HLA-haploidentical related donor (aged 12 to 75 years) with donor/recipient match based on a minimum of intermediate resolution DNA based Class I typing of the A and B locus (at least 2/4 class I allele)
  • Karnofsky Performance Status ≥ 60%
  • Adequate organ function within 14 days of study registration (28 days for pulmonary and cardiac) defined as:

    • Creatinine: ≤ 2.0 mg/dL
    • Hepatic: AST and ALT < 3 x upper limit of institutional normal
    • Pulmonary Function: oxygen saturation ≥ 90% on room air; PFT's required only if symptomatic or prior known impairment - must have pulmonary function >50% corrected DLCO and FEV1.
    • Cardiac Function: 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 systemic immunosuppressive medications for at least 3 days prior to NK cell infusion (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
  • 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
  • Received any investigational agent within the 14 days before the start of study treatment (1st dose of fludarabine)
  • Prior ALT-803
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03050216
Other Study ID Numbers  ICMJE 2016LS056
MT2016-05 ( Other Identifier: Masonic Cancer Center, University of Minnesota )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party Masonic Cancer Center, University of Minnesota
Study Sponsor  ICMJE Masonic Cancer Center, University of Minnesota
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Claudio Brunstein, MD, PhD Masonic Cancer Center, University of Minnesota
PRS Account Masonic Cancer Center, University of Minnesota
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP