QUILT-3.033: Haplo NK With SQ ALT-803 for Adults With Relapsed or Refractory AML

University of Minnesota (UMN)

Status and phase: Completed; Phase 2

Conditions: Acute Myeloid Leukemia

Treatments: Biological: ALT-803

Study type: Interventional

Funder types: Other

Identifiers

NCT03050216

2016LS056

MT2016-05 (Other Identifier)

Details and patient eligibility

About

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).

Enrollment: 8 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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8 participants in 1 patient group

Cy, FLU, Haplo NK and ALT-803

Experimental group

Description:

Preparative Regimen of Fludarabine and Cyclophosphamide ALT-803 Activation of Donor NK Cells ALT-803 to Facilitate NK Cell Survival and Expansion

Treatment:

Biological: ALT-803