CD3/CD19 Depleted or CD3 Depleted/CD56 Selected Haploid Donor Natural Killer Cell Treatment in Older AML in First Complete Remission

NCT01639456 | Withdrawn Phase 2 DMC

• 2 other identifiers: 2011LS151MT2011-26
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

This is a phase II trial designed to test the safety and efficacy (disease free survival \[DFS\]) of related donor HLA-haploidentical NK-cell based therapy for the treatment of acute myelogenous leukemia (AML). The natural killer (NK) cell product will be given to patients 60 years and older who are in a first complete remission after 1 or 2 courses of standard AML induction. After a preparative regimen of cyclophosphamide and fludarabine, patients will receive a single infusion of either 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

Keywords

acute myelogenous leukemia

Outcome Measures

Primary Outcomes (1)

• Disease-Free Survival

  the length of time after treatment ends that a patient survives without any signs or symptoms of that cancer or any other type of cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works.

  1 Year

Secondary Outcomes (6)

• Incidence of Infusional Toxicities

  Day 100

• Incidence of Chronic Graft-Versus-Host Disease (GVHD)

  1 Year

• Incidence of Acute Graft-Versus-Host Disease (GVHD)

  Day 100

• Treatment-Related Mortality

  Day 100, 1 Year and 2 Years

• Overall Survival

  1 Year and 2 Years

Study Arms (2)

Patients Using CD3-/CD19- NK cell product

EXPERIMENTAL

Patients receive the apheresis product (collected day -1: enriched for NK cells using the CliniMACS® CD3 and CD19 Reagent System in combination with the large-scale tubing set (Miltenyi Biotec) to simultaneously deplete CD3+ cells to remove T-lymphocytes and deplete CD19+ cells to remove B-lymphocytes (CD3-/CD19- natural killer cells). Patients will also receive Cyclophosphamide, Fludarabine and Aldesleukin.

Biological: CD3-/CD19- natural killer cells; Device: CliniMACS® CD3 and CD19 Reagent System; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Aldesleukin

Patients Using CD3-/CD56+ purified NK cell product

EXPERIMENTAL

Patients receive the apheresis product (collected day -1): purified for NK cells using the CliniMACS® CD3 Reagent System (Miltenyi Biotec) in combination with the large-scale tubing set to deplete CD3+ cells and then use the CliniMACS® CD56 Reagent System to enrich CD56+ NK cells (CD3-CD56+ natural killer cells). Patients will also receive Cyclophosphamide, Fludarabine and Aldesleukin.

Biological: CD3-CD56+ natural killer cells; Device: CliniMACS® CD3 and CD19 Reagent System; Device: CliniMACS® CD56 Reagent System; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Aldesleukin

Interventions

CD3-/CD19- natural killer cells BIOLOGICAL

Infused on Day 0. The final CD3-/CD19- product must contain at least 20% NK cells based on previous studies using this cell product processing technique. The entire cell product will be administered except in cases where the T cell count exceeds the T cell infusion threshold. In such situations, the product volume will be adjusted to meet the lot release criteria.

Patients Using CD3-/CD19- NK cell product

CD3-CD56+ natural killer cells BIOLOGICAL

Infused on Day 0. The final CD3-/CD56+ product must contain at least 70% NK cells based on a previous study using this cell product processing technique. The entire cell product will be administered except in cases where the T cell count exceeds the T cell infusion threshold. In such situations, the product volume will be adjusted to meet the lot release criteria.

Patients Using CD3-/CD56+ purified NK cell product

CliniMACS® CD3 and CD19 Reagent System DEVICE

In combination used to simultaneously deplete CD3+ cells to remove T-lymphocytes and deplete CD19+ cells to remove B-lymphocytes (CD3-/CD19-). The entire cell product will be administered except in cases where the T cell count exceeds the T cell infusion threshold. In such situations, the product volume will be adjusted to meet the lot release criteria.

Patients Using CD3-/CD19- NK cell product; Patients Using CD3-/CD56+ purified NK cell product

CliniMACS® CD56 Reagent System DEVICE

CliniMACS® CD3 and CD19 Reagent System will be used in addition to CliniMACS® CD56 Reagent System to enrich CD56+ NK cells. The entire cell product will be administered except in cases where the T cell count exceeds the T cell infusion threshold. In such situations, the product volume will be adjusted to meet the lot release criteria.

Patients Using CD3-/CD56+ purified NK cell product

Cyclophosphamide DRUG

Infused intravenously 60 mg/kg x day -5

Also known as: Cytoxin

Patients Using CD3-/CD19- NK cell product; Patients Using CD3-/CD56+ purified NK cell product

Fludarabine DRUG

Fludarabine 25 mg/m2 x days -6 through -2

Also known as: Fludara

Patients Using CD3-/CD19- NK cell product; Patients Using CD3-/CD56+ purified NK cell product

Aldesleukin DRUG

IL-2 subcutaneously at 6 million units every other day for 6 doses - begin evening of the NK cell infusion.

Also known as: IL-2

Patients Using CD3-/CD19- NK cell product; Patients Using CD3-/CD56+ purified NK cell product

Eligibility Criteria

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

You may qualify if:

• Diagnosis of acute myelogenous leukemia (except acute promyelocytic leukemia) in a first complete remission (CR1) and meet the following criteria:
• Meets the definition of complete remission by morphologic criteria including \<5% blasts in a moderately cellular (\> 20% cellularity) or cellular marrow.
• Complete remission (CR) was achieved after no more than 2 cycles of standard induction chemotherapy. Early re-induction therapy based on residual disease on a day 14 bone marrow (BM) will count as a 2nd cycle. Prior therapy with demethylating agents (i.e. azacitidine) is allowed, but patients must have attained CR after standard cytotoxic therapy (defined as absolute neutrophil count (ANC) \> 1000 cells/μL, platelets \> 100 x 10\^9/L)
• No more than 3 months have lapsed from attainment of CR1
• No acute myelogenous leukemia (AML) consolidation therapy administered prior to enrollment
• Not a candidate for allogeneic stem cell transplantation
• ≥ 60 years of age
• Karnofsky performance status ≥ 70%
• Available related HLA haploidentical natural killer (NK) cell donor (sibling, offspring, or offspring of an HLA identical sibling) by at least Class I serologic typing at the A\&B locus (donor age 18-75 years)
• At least 30 days since last dose of chemotherapy
• Adequate organ function within 14 days of enrollment defined as:
• Creatinine: ≤ 2.0 mg/dL
• Hepatic: aspartate aminotransferase (SGOT) and alanine aminotransferase (SGPT) \< 5 x upper limit of institutional normal (ULN)
• Pulmonary: oxygen saturation ≥ 90% on room air
• 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)

You may not qualify if:

• Biphenotypic acute leukemia
• New progressive pulmonary infiltrates on screening chest x-ray or chest Computed Tomography scan that has not been evaluated with bronchoscopy (when 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).
• Uncontrolled bacterial, fungal, or viral infections including human immunodeficiency virus (HIV) - chronic asymptomatic viral hepatitis is allowed
• Pleural effusion large enough to be detectable on chest x-ray
• Known hypersensitivity to one or more of the study agents
• Donor Selection:
• Related donor (sibling, offspring, or offspring of an HLA identical sibling) 18-75 years of age
• At least 40 kilograms
• In general good health as determined by the medical provider
• Negative for hepatitis and HIV on donor viral screen
• HLA-haploidentical donor/recipient match by at least Class I serologic typing at the A\&B locus
• Not pregnant
• Voluntary written consent

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead
• Miltenyi Biomedicine GmbH: collaborator

Study Sites (2)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; aldesleukin; 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

Study Officials

• Jeffrey S. Miller, M.D.

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2012
• First Posted: July 12, 2012
• Study Start: October 1, 2013
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2017
• Last Updated: December 2, 2017

Record last verified: 2017-11

Locations

US (2)