CD3/CD19 Depleted or CD3 Depleted/CD56 Selected Haploidentical Donor Natural Killer (NK) Cell Based Therapy for AML Patients Not in CR

NCT03152526 | Terminated Results DMC FDA Device

• 1 other identifier: MT-2014-02
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 3

Brief Summary

This is a phase II trial designed to test the safety and efficacy (complete response \[CR\]) of related donor HLA-haploidentical NK-cell based therapy for the treatment of acute myelogenous leukemia (AML). Patients with newly diagnosed AML who failed to achieve a complete remission (CR) after one or two standard induction attempts receive after a preparative regimen of cyclophosphamide and fludarabine a single infusion of CD3-/CD19- NK cells or CD3-/CD56+ NK cells followed by a short course of Interleukin-2 (IL-2) to facilitate NK cell survival and expansion.

Conditions

Acute Myelogenous Leukemia

Outcome Measures

Primary Outcomes (1)

• The Primary Endpoint of the Study is Complete Remission (±3 Days)

  Both the number of patients with leukemia in complete remission and the number of patients with leukemia not in complete remission will be reported. Leukemia remission status will be assessed according to the Revised Recommendations of The International Working Group (J Clin Oncol 21:4642-4649, 2003).

  On Day+42 (+/- 3 days) after NK cell infusion

Secondary Outcomes (1)

• The Secondary Endpoint is the Expansion and Persistence of NK Cells to be Used for the Remainder of the Study.

  Day+7 to Day+42 after NK cell infusion

Study Arms (1)

Single-arm trial

OTHER

Multi-center, open-label, single-arm, phase I/II clinical trial

Device: Interventions

Interventions

Interventions DEVICE

CliniMACS® CD3 and CD19 Reagent System

Also known as: Devise

Single-arm trial

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed with acute myelogenous leukemia (except acute promyelocytic leukemia) and has failed one or two prior standard induction attempts. Failure is defined as:
• ≥ 30% bone marrow blasts with at least 20% cellularity at mid-cycle bone marrow biopsy or residual AML on subsequent\~ day 28 bone marrow biopsy by morphology, flow, PCR or FISH
• Patients enrolling after only 1 failed induction attempt must meet at least one of the following additional eligibility criteria of high risk: ≥ 60 years of age adverse cytogenetics or molecular characteristics
• AML that progressed out of myelodysplastic syndrome (MDS) is eligible if the patient did not receive treatment directed at the MDS
• HLA-haploidentical related donor (aged 12 to 70 years)
• ≥ 18, but \< 75 years of age
• Karnofsky performance status ≥ 60%
• Adequate organ function within 14 days of study registration (30 days for pulmonary and cardiac) as defined in section 4.5
• Ability to be off prednisone and other immunosuppressive drugs for at least 3 days prior to the NK cell infusion (excluding preparative regimen pre-meds)
• No prior hematopoietic transplant
• Not pregnant or lactating
• Sexually active females of childbearing potential and males with partners of child bearing potential must agree to use birth control

You may not qualify if:

• Pregnant or lactating as the treatments used in this study includes drugs that are FDA Pregnancy Category D.
• Acute leukemias of ambiguous lineage
• AML that transformed from previously treated myelodysplastic syndromes
• Prior hematopoietic transplant
• New or progressive pulmonary infiltrates on screening chest x-ray or chest CT scan that has not been cleared 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 - chronic asymptomatic viral hepatitis is allowed
• Known hypersensitivity to one or more of the study agents used

Sponsors & Collaborators

• Miltenyi Biotec B.V. & Co. KG: lead
• Masonic Cancer Center, University of Minnesota: collaborator
• University of Chicago: collaborator
• Ohio State University: collaborator

Study Sites (3)

Universtiy of Chicago

Chicago, Illinois, 60637, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Methods

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Investigative Techniques

Limitations and Caveats

As a result of poor subject accrual (n=1), statistically relevant efficacy data cannot be defined according to the protocol.

Results Point of Contact

• Title: Clinical Project Manager
• Organization: Miltenyi Biotec

lorenb@miltenyibiotec.com

617-218-0055

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: In summary, the study will take place in two parts: Stage 1: Enroll 24 patients with 1:1 randomization for NK cell processing (CD3-/CD19- versus CD3-/CD56+) Stage 2: Enroll an additional 17 patients using the optimal NK cell product identified during stage 1. If neither product achieves success at the end of stage 1, the study will stop and the platform redesigned

Study Record Dates

• First Submitted: February 28, 2017
• First Posted: May 15, 2017
• Study Start: October 18, 2017
• Primary Completion: March 21, 2018
• Study Completion: March 21, 2018
• Last Updated: July 9, 2020
• Results First Posted: May 7, 2019

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)