Haploidentical Donor Natural Killer Cell Infusion With IL-15 in Acute Myelogenous Leukemia (AML)

NCT01385423 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: 2010LS063MT2010-101009M89012
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center, "modified standard design" dose escalation study designed to determine the maximum tolerated, minimum efficacious dose (MTD/MED) of IL-15 (Intravenous Recombinant Human IL-15) and incidence of donor natural killer (NK) cell expansion by day +14 when given after haploidentical donor NK cells in patients with relapse or refractory acute myelogenous leukemia (AML).

Conditions

Acute Myelogenous Leukemia; Myelodysplastic Syndrome

Keywords

acute myelogenous leukemia; natural killer cells; haploidentical donor

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated/Minimum Efficacious Dose

  Determine the maximum tolerated, minimum efficacious dose (MTD/MED) of recombinant human IL-15; dose limiting toxicity (DLT) occurring during the first 42 days after the NK cell infusion; MED = if 2 of 3 patients or 4 of 6 patients has an in vivo NK cell count \>2500, then dose escalation with cease as it will be in the range of a biologic dose which may achieve the goal of in vivo expansion without pushing IL-15 doses higher to toxicity.

  Day 42

Secondary Outcomes (3)

• Incidence of Expansion of Natural Killer Cells

  Day 14 after Infusion

• Treatment Related Mortality (TRM)

  Day 1 of Treatment until Day of Death

• Rate of CRp

  Day 28-42

Study Arms (1)

IL-15 Patients with AML

EXPERIMENTAL

Adults with Refractory or Relapsed Acute Myelogenous Leukemia (AML) treated with preparative regimen and Intravenous Recombinant Human IL-15 (rhIL-15)

Drug: Preparative Regimen; Biological: Intravenous Recombinant Human IL-15 (rhIL-15)

Interventions

Preparative Regimen DRUG

Fludarabine 25 mg/m\^2 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)

Also known as: Fludara, Cytoxan

IL-15 Patients with AML

Intravenous Recombinant Human IL-15 (rhIL-15) BIOLOGICAL

IL-15 at assigned dose (0.25, 0.5, 0.75 1, 2 and 3 mcg/kg for 3 to 6 patients) intravenously (IV) over 30 minutes once a day beginning day +1 and continuing for 12 doses

Also known as: IL-15

IL-15 Patients with AML

Eligibility Criteria

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

You may qualify if:

• ≥ 18 years of age
• Meets one of the following disease criteria:
• Primary acute myelogenous leukemia (AML) induction failure: no complete response (CR )after 2 or more induction attempts
• Relapsed AML or Secondary AML (from MDS or treatment-related): not in CR after 1 or more cycles of standard induction therapy. For patients \> 60 years of age the 1 cycle of standard chemotherapy is not required if either of the following is met:
• relapse within 6 months of last chemotherapy
• blast count \<30% within 10 days of starting protocol
• AML relapsed \> 2 months after transplant who do not have the option of donor lymphocyte infusions (e.g. recipients of autologous or umbilical cord blood \[UCB\] transplants)
• Patients with prior central nervous system (CNS) involvement are eligible provided that it has been treated and cerebrospinal fluid (CSF) is clear for at least 2 weeks prior to enrollment. CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment.
• Available related HLA-haploidentical donor (3-5 of 6 HLA-A, B and C)
• Karnofsky Performance Status \> 50%
• Adequate organ function defined as:
• Creatinine: ≤ 2.0 mg/dL
• Hepatic: Liver function tests (LFT's) \< 5 times upper limit of institutional normal (ULN)
• Pulmonary Function: oxygen saturation ≥ 90% on room air and pulmonary function \>50% corrected DLCO and FEV1 Testing required only if symptomatic or prior known impairment.
• Cardiac Function: Ejection fraction (EF) ≥ 40%, no uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities

You may not qualify if:

• Bi-phenotypic acute leukemia
• Transplant \< 60 days prior to study enrollment
• 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 within 14 days of study treatment start
• Active autoimmune disease
• History of severe asthma, presently on chronic medications (a history of mild asthma not requiring therapy is eligible)
• New or progressive pulmonary infiltrates on screening chest x-ray or chest CT scan that has not been evaluated with bronchoscopy, if feasible. 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). Surgical resection waives any waiting requirements.
• Uncontrolled bacterial or viral infections - chronic asymptomatic viral hepatitis is allowed
• Pleural effusion large enough to be detectable on chest x-ray
• Known hypersensitivity to any of the study agents used
• Received investigational drugs within the 14 days before enrollment
• Known active CNS involvement
• Criteria For Initial Donor Selection:
• Related donors (sibling, parent, offspring, parent or offspring of an HLA identical sibling)
• years of age
• At least 40 kilogram body weight

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (1)

• 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.

  PMID: 31266741 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

fludarabine phosphate; Cyclophosphamide; Interleukin-15

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Jeffrey S Miller, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2011
• First Posted: June 30, 2011
• Study Start: September 1, 2011
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: July 24, 2025

Record last verified: 2025-07

Locations

US (1)