Clinical trial NCT03050216: QUILT-3.033: Haplo NK With SQ ALT-803 for Adults With Relapsed or Refractory AML
Official title: QUILT-3.033: Haploidentical Donor Natural Killer (NK) Cell Infusion With Subcutaneous ALT-803 in Adults With Refractory or Relapsed Acute Myelogenous Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2017-02-10
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: 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, azacitidine) 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

Primary outcomes:
measure: Number of Participants With Complete Remission With or Without Incomplete Platelet Recovery
timeFrame: Day 42 post NK cell infusion
Secondary outcomes:
measure: Incidence of in Vivo Expansion ≥100 of Donor Derived NK Cells Per /μl Blood
timeFrame: Day 14 post NK cell infusion
measure: Number of Participants Experiencing ALT-803 Associated Toxicity
timeFrame: Day 0
measure: Number of Participants Experiencing ALT-803 Associated Toxicity
timeFrame: Day 5
measure: Number of Participants Experiencing ALT-803 Associated Toxicity
timeFrame: Day 7
measure: Number of Participants Experiencing ALT-803 Associated Toxicity
timeFrame: Day 10
measure: Number of Participants With Treatment Related Mortality
timeFrame: 6 months post-therapy
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center at University of Minnesota
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Jeffrey Miller, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Berrien-Elliott MM, Becker-Hapak M, Cashen AF, Jacobs M, Wong P, Foster M, McClain E, Desai S, Pence P, Cooley S, Brunstein C, Gao F, Abboud CN, Uy GL, Westervelt P, Jacoby MA, Pusic I, Stockerl-Goldstein KE, Schroeder MA, DiPersio JF, Soon-Shiong P, Miller JS, Fehniger TA. Systemic IL-15 promotes allogeneic cell rejection in patients treated with natural killer cell adoptive therapy. Blood. 2022 Feb 24;139(8):1177-1183. doi: 10.1182/blood.2021011532.