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

NCT03050216 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2016LS056MT2016-05
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Complete Remission With or Without Incomplete Platelet Recovery

  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)

  Day 42 post NK cell infusion

Secondary Outcomes (6)

• Incidence of in Vivo Expansion ≥100 of Donor Derived NK Cells Per /μl Blood

  Day 14 post NK cell infusion

• Number of Participants Experiencing ALT-803 Associated Toxicity

  Day 0

• Number of Participants Experiencing ALT-803 Associated Toxicity

  Day 5

• Number of Participants Experiencing ALT-803 Associated Toxicity

  Day 7

• Number of Participants Experiencing ALT-803 Associated Toxicity

  Day 10

Study Arms (1)

Cy, FLU, Haplo NK and ALT-803

EXPERIMENTAL

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

Biological: ALT-803

Interventions

ALT-803 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

Cy, FLU, Haplo NK and ALT-803

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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
• 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 followed by 5+2 counts as TWO induction attempts
• Use of hydroxyurea is permitted to control blasts until Day -3 per Section 8.7
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (1)

• 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.

  PMID: 34797911 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

ALT-803

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Dr.Claudio G. Brunstein MD, PhD
• Organization: Masonic Cancer Center, University of Minnesota

bruns072@umn.edu

612 625 3918

Study Officials

• Jeffrey Miller, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2017
• First Posted: February 10, 2017
• Study Start: May 16, 2017
• Primary Completion: December 15, 2019
• Study Completion: December 15, 2019
• Last Updated: July 18, 2023
• Results First Posted: November 27, 2020

Record last verified: 2023-07

Locations

US (1)