MT2014-25: Haplo NK With SQ IL-15 in Adult Relapsed or Refractory AML Patients

NCT ID: NCT02395822

Last Updated: 2018-02-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-01
• Study Completion Date: 2016-12-01

Brief Summary

A phase II trial of CD3/CD19 depleted, IL-15 activated, donor natural killer (NK) cells in adults and subcutaneous IL-15 given after a preparative regimen for the treatment of relapsed or refractory acute myelogenous leukemia (AML). The primary objective is to study the potential efficacy of NK cells and IL-15 to achieve complete remission while maintaining safety.

Conditions

Acute Myelogenous Leukemia

Study Design

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

Study Groups

Preparative Regimen and SubQ rHuIL-15

Preparative Regimen of Fludarabine and Cyclophosphamide

IL-15 Activation of Donor NK Cells:

IL-15 to Facilitate NK Cell Survival and Expansion

Group Type: EXPERIMENTAL

IL-15

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 (if < 4 months from prior transplant, omit day -4 dose)

IL-15 Activated 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 activated by overnight incubation with10 ng/ml IL-15 under GMP conditions and infused on day 0.

IL-15 to Facilitate NK Cell Survival and Expansion:

IL-15 at 2 mcg/kg subcutaneously (SC) beginning day +1, once a day for 5 days followed by a 2 day rest, and then once a day for 5 days for 10 doses total

Interventions

IL-15

Preparative Regimen:

Fludarabine 25 mg/m2 x 5 days start day -6 Cyclophosphamide 60 mg/kg x 2 days on day -5 and -4 (if < 4 months from prior transplant, omit day -4 dose)

IL-15 Activated 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 activated by overnight incubation with10 ng/ml IL-15 under GMP conditions and infused on day 0.

IL-15 to Facilitate NK Cell Survival and Expansion:

IL-15 at 2 mcg/kg subcutaneously (SC) beginning day +1, once a day for 5 days followed by a 2 day rest, and then once a day for 5 days for 10 doses total

Intervention Type: BIOLOGICAL

Other Intervention Names

Interleukin-15

Eligibility Criteria

Inclusion Criteria

• Meets ONE of the following disease criteria:

1. Primary AML induction failure: no CR after 2 or more induction attempts

2. Relapsed AML or Secondary AML (from MDS or treatment related): not in CR after 1 or more cycles of standard re-induction therapy

3. AML relapsed > 2 months after transplant: No re-induction required, and no more than 1 re-induction cycle is allowed.

4. Relapsed AML for patients > 60 years of age the 1 cycle of standard chemotherapy is not required if either of the following criteria is met:

• Relapse within 6 months of last chemotherapy
• BM blast count < 30% within 10 days of starting protocol therapy
• Available related HLA-haploidentical donor (aged 14 to 75 years) by at least Class I serologic typing at the A&B locus
• Karnofsky Performance Status ≥ 60%
• Patients must have adequate organ within 14 days (28 days for pulmonary and cardiac) of study registration
• Able to be off prednisone or other immunosuppressive medications for at least 3 days prior to NK cell infusion (excluding preparative regimen pre-medications).
• Agrees to use contraception prior to study entry and for the duration of study participation.

Exclusion Criteria

• Bi-phenotypic acute leukemia.
• Transplant < 60 days prior to study enrollment.
• Active autoimmune disease.
• History of severe asthma
• Uncontrolled intercurrent illness
• New or progressive pulmonary infiltrates on screening chest x-ray or chest CT scan that has not been evaluated with bronchoscopy
• Pleural effusion large enough to be detectable on chest x-ray.
• Pregnant women
• History of HIV, active or chronic hepatitis B, hepatitis C or HTLV-I infection
• Known hypersensitivity to any of the study agents used
• Received investigational drugs within the 14 days of study registration.
• Known active CNS involvement.

Criteria For Initial Donor Selection:

• Related donors (sibling, parent, offspring, parent or offspring of an HLA identical sibling).
• 14-75 years of age.
• At least 40 kilogram body weight.
• In general good health as determined by the evaluating medical provider.
• HLA-haploidentical donor/recipient match by at least Class I serologic typing at the A&B locus.
• Not pregnant.
• Able and willing to undergo apheresis.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

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

Cooley S, He F, Bachanova V, Vercellotti GM, DeFor TE, Curtsinger JM, Robertson P, Grzywacz B, Conlon KC, Waldmann TA, McKenna DH, Blazar BR, Weisdorf DJ, Miller JS. First-in-human trial of rhIL-15 and haploidentical natural killer cell therapy for advanced acute myeloid leukemia. Blood Adv. 2019 Jul 9;3(13):1970-1980. doi: 10.1182/bloodadvances.2018028332.

Reference Type: DERIVED

PMID: 31266741 (View on PubMed)

Other Identifiers

2014LS092

Identifier Type: -

Identifier Source: org_study_id