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

NCT ID: NCT03050216

Last Updated: 2023-07-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-16
• Study Completion Date: 2019-12-15

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).

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

ALT-803

Intervention Type: BIOLOGICAL

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

Interventions

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

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeffrey Miller, MD

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 34797911 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

MT2016-05

Identifier Type: OTHER

Identifier Source: secondary_id

2016LS056

Identifier Type: -

Identifier Source: org_study_id