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

Primary Purpose

Acute Myelogenous Leukemia

Status

Terminated

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Interventions

About this trial

This is an interventional treatment trial for Acute Myelogenous Leukemia

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

Universtiy of Chicago
University of Minnesota
Ohio State University

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Single-arm trial

Arm Description

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

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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

Successful expansion and persistence of NK cells is defined as ≥ 100 donor derived NK cells per µl blood.

Full Information

NCT ID

NCT03152526

First Posted

February 28, 2017

Last Updated

July 8, 2020

Sponsor

Miltenyi Biotec B.V. & Co. KG

Collaborators

Masonic Cancer Center, University of Minnesota, University of Chicago, Ohio State University

1. Study Identification

Unique Protocol Identification Number

NCT03152526

Brief Title

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

Official Title

A Randomized Trial Comparing CD3/CD19 Depleted or CD3 Depleted/CD56 Selected Haploidentical Donor Natural Killer (NK) Cell Based Therapy for Adults With Acute Myelogenous Leukemia Who Have Failed 1 or 2 Induction Attempts

Study Type

Interventional

2. Study Status

Record Verification Date

February 2020

Overall Recruitment Status

Terminated

Why Stopped

Slow enrollment

Study Start Date

October 18, 2017 (Actual)

Primary Completion Date

March 21, 2018 (Actual)

Study Completion Date

March 21, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Miltenyi Biotec B.V. & Co. KG

Collaborators

Masonic Cancer Center, University of Minnesota, University of Chicago, Ohio State University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Device Product Not Approved or Cleared by U.S. FDA

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

This trial uses a Simon's two-stage design to estimate the complete remission rate at day +42 post NK cell infusion. The trial includes an initial randomized sub- study of 24 patients during stage 1 to choose which of the enriched NK cell products (CD3-/CD19- versus CD3-/CD56+) should be used to complete the trial based on successful in vivo NK cell expansion. This parameter is defined as 40% donor DNA and 40% of lymphocytes are NK cells at day 7 post infusion OR 20% donor DNA and 20% of lymphocytes are NK cells at day 14 post infusion. Twelve patients will be randomized to each product. Enrollment Plan: 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Myelogenous Leukemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Model Description

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

Masking

None (Open Label)

Allocation

N/A

Enrollment

1 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Single-arm trial

Arm Type

Other

Arm Description

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

Intervention Type

Device

Intervention Name(s)

Interventions

Other Intervention Name(s)

Devise

Intervention Description

CliniMACS® CD3 and CD19 Reagent System

Primary Outcome Measure Information:

Title

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

Description

Time Frame

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

Secondary Outcome Measure Information:

Title

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

Description

Successful expansion and persistence of NK cells is defined as ≥ 100 donor derived NK cells per µl blood.

Time Frame

Day+7 to Day+42 after NK cell infusion

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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

Facility Information:

Facility Name

Universtiy of Chicago

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60637

Country

United States

Facility Name

University of Minnesota

City

Minneapolis

State/Province

Minnesota

ZIP/Postal Code

55455

Country

United States

Facility Name

Ohio State University

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43210

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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