Haploidentical Natural Killer Cells to Treat Refractory or Relapsed Acute Myelogenous Leukemia (AML)

NCT01106950 | Terminated Phase 2 Results DMC

• 3 other identifiers: 2010LS010MT2010-021003M79954
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II therapeutic study of related donor HLA-haploidentical NK-cell based therapy after a high dose of fludarabine/cyclophosphamide with denileukin diftitox preparative regimen for the treatment of poor prognosis acute myelogenous leukemia (AML).

Conditions

Leukemia, Myelogenous, Acute

Keywords

acute myelogenous leukemia; primary acute myelogenous leukemia; secondary acute myelogenous leukemia; relapsed acute myelogenous leukemia

Outcome Measures

Primary Outcomes (1)

• Percent of Patients With Successful Expansion of Natural Killer Cells After Infusion

  The primary objective of this study was to estimate the incidence of in vivo expansion of natural killer (NK) cells 14 days after infusion of an allogeneic donor product enriched for NK progenitors. Successful in vivo donor NK cell expansion was defined by measuring an absolute circulating donor-derived NK cell count of \>100 cells/ul in the patient's peripheral blood 14 days after infusion.

  Day 14

Secondary Outcomes (5)

• Percent of Patients With Complete Remission of Disease

  At least 4 weeks after last dose (28 days)

• Percent of Patients With Disease Free Survival

  Month 6

• Percent of Patients With Incidence of Relapse

  Month 6

• Number of Patients With Treatment-Related Death

  Day 100

• Percent of Patients With Natural Killer Cell Expansion Versus KIR Genotype Versus Treg Depletion

  Day 14

Study Arms (1)

Treated Patients

EXPERIMENTAL

Patients are treated with donor natural killer cells, fludarabine, cyclophosphamide, Denileukin diftitox, Donor lymphapheresis and IL-2.

Biological: Natural Killer Cells; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Denileukin diftitox; Procedure: Donor lymphapheresis; Drug: IL-2

Interventions

Natural Killer Cells BIOLOGICAL

Given by infusion on Day 0. The product is T cell-depleted (CD3-) and B cell-depleted (CD19). Target dose for infusion is \< or = 8 x 10\^7 nucleated cells/kilogram.

Treated Patients

Fludarabine DRUG

Administered as a 1 hour intravenous infusion once a day for 5 doses beginning on day -6.

Also known as: Fludara

Treated Patients

Cyclophosphamide DRUG

Administered as a 2 hour intravenous infusion with high volume fluid flush and mesna per institutional guidelines on day -5 and -4 one hour after fludarabine infusion. (Day -4 administration may be omitted if patient has had a transplant in the previous 4 months.)

Also known as: Cytoxan

Treated Patients

Denileukin diftitox DRUG

12 ug/kg/day will be administered on day -1 and day -2 intravenously.

Also known as: Ontak

Treated Patients

Donor lymphapheresis PROCEDURE

Day -1 before planned NK cell infusion, the donor will undergo lymphapheresis (Removal of lymphocytes from donated blood, with the remainder of the blood retransfused into the donor).

Treated Patients

IL-2 DRUG

Administered after NK cell infusion, 10 million units every other day for a total of 6 doses. (Patients weighing less than 45 kilograms will receive a dose of 5 million units/m\^2 every other day for 6 doses).

Also known as: Interleukin-2

Treated Patients

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 2 years of age
• Meets one of the following disease criteria:
• Primary acute myelogenous leukemia (AML) induction failure: no complete remission (CR) after 2 or more induction attempts
• Relapsed acute myelogenous leukemia (AML): not in CR after 1 or more cycles of standard re-induction therapy. 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
• blast count \< 30% within 10 days of starting protocol therapy
• Secondary AML from myelodysplastic syndrome (MDS)
• 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 CSF is clear for at least 2 weeks or magnetic resonance imaging (MRI) stable 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% or Lansky Play score \> 50
• Adequate organ function defined as:
• Creatinine: ≤ 2.0 mg/dL (for pediatric patients - ClCr \> 50 ml/min or age adjusted Cr)
• Hepatic: Liver function tests (LFT's) \< 5 x upper limit of institutional normal (ULN)
• Pulmonary Function: oxygen saturation ≥ 90% on room air and pulmonary function \>50% corrected Diffusion lung capacity for carbon monoxide (DLCO) and Forced expiratory volume in one second (FEV1) Oxygen saturation \[\>92%\] can be used in child where pulmonary function tests (PFT's) cannot be obtained. (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
• New or progressive pulmonary infiltrates on screening chest x-ray or chest computated tomography (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

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)

• Bachanova V, Cooley S, Defor TE, Verneris MR, Zhang B, McKenna DH, Curtsinger J, Panoskaltsis-Mortari A, Lewis D, Hippen K, McGlave P, Weisdorf DJ, Blazar BR, Miller JS. Clearance of acute myeloid leukemia by haploidentical natural killer cells is improved using IL-2 diphtheria toxin fusion protein. Blood. 2014 Jun 19;123(25):3855-63. doi: 10.1182/blood-2013-10-532531. Epub 2014 Apr 9.

  PMID: 24719405 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

IL32 protein, human; fludarabine; fludarabine phosphate; Cyclophosphamide; denileukin diftitox; Interleukin-2

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic 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; Lymphokines; Proteins; Biological Factors

Results Point of Contact

• Title: Jeffrey S. Miller, M.D.
• Organization: Masonic Cancer Center, University of Minnesota

mille011@umn.edu

612-625-7409

Study Officials

• Jeffrey S. Miller, M.D.

  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: April 19, 2010
• First Posted: April 20, 2010
• Study Start: July 1, 2010
• Primary Completion: October 1, 2011
• Study Completion: December 1, 2012
• Last Updated: December 28, 2017
• Results First Posted: June 26, 2013

Record last verified: 2017-12

Locations

US (1)