Alloreactive Haploidentical Natural Killer (NK) Cells With Busulfan and Fludarabine/ATG

NCT01390402 | Completed Phase 2 Results

• 3 other identifiers: 2010-0099NCI-2011-01463P01CA049639
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if giving a kind of immune cell called natural killer (NK) cells after chemotherapy will improve the response to a stem cell transplant in patients with CML. The safety of this treatment will also be studied.

Conditions

Leukemia; Chronic Myelogenous Leukemia

Keywords

Alloreactive haploidentical NK cells; Natural killer cells; Stem Cell Transplantation; Immune cells; Chronic myelogenous leukemia; CML; Human leukocyte antigen; HLA; Graft-vs-host disease; GVHD; Antithymocyte globulin; ATG; Thymoglobulin; Interleukin-2; IL-2; Aldesleukin; Proleukin; Fludarabine; Fludarabine phosphate; Fludara; Tacrolimus; Prograf; Busulfan; Busulfex; Myleran; Methotrexate

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Molecular Complete Remission at 3 Month Post Transplant

  Molecular Complete Remission is defined as participant alive and engrafted with molecular complete remission 100 days post transplant where molecular complete response is no BCR-ABL transcripts detected and engraftment is defined as the evidence of donor derived cells (more than 95%) by chimerism studies in the presence of neutrophil recovery by day 28 post stem cell infusion.

  Baseline to up to 4 months post-transplant

Study Arms (1)

NK Infusion + Chemotherapy

EXPERIMENTAL

Fludarabine 40 mg/m2 intravenous (IV) daily for 4 days, immediately followed by Busulfan 130 mg/ m2 IV every 24 hours and NK cell infusion IV.

Drug: Fludarabine; Drug: Busulfan; Procedure: NK cell infusion:; Drug: Interleukin-2; Drug: Anti-Thymocyte Globulin; Procedure: Allogeneic related Stem Cell Transplant; Drug: Tacrolimus; Drug: Methotrexate; Drug: G-CSF

Interventions

Fludarabine DRUG

40 mg/m2 intravenous over one (1) hour on each of four (4) consecutive days, Days -13 to -10.

Also known as: Fludarabine Phosphate, Fludara

NK Infusion + Chemotherapy

Busulfan DRUG

130 mg/ m2 by vein for 2 doses on Days -11 to -10.

Also known as: Busulfex, Myleran

NK Infusion + Chemotherapy

NK cell infusion: PROCEDURE

Natural killer cell infusion will be administered by vein on Day -8.

NK Infusion + Chemotherapy

Interleukin-2 DRUG

0.5 million units subcutaneously daily for 5 days on Day -8 to day -4.

Also known as: IL-2, Aldesleukin, Proleukin

NK Infusion + Chemotherapy

Anti-Thymocyte Globulin DRUG

2.5 mg/kg by vein for 3 doses on Days -3 to -1.

Also known as: ATG, Thymoglobulin

NK Infusion + Chemotherapy

Allogeneic related Stem Cell Transplant PROCEDURE

Allogeneic related stem cell transplant by vein on day 0.

NK Infusion + Chemotherapy

Tacrolimus DRUG

Starting dose of 0.015 mg/kg (ideal body weight) as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml.

Also known as: Prograf

NK Infusion + Chemotherapy

Methotrexate DRUG

5 mg/m2 by vein Days 1, 3 and 6 post transplant.

NK Infusion + Chemotherapy

G-CSF DRUG

5 mcg/kg/day subcutaneously beginning on Day + 7, and continuing until the absolute neutrophil count (ANC) is \> 500 x 10/L for 3 consecutive days.

Also known as: Filgrastim, Neupogen

NK Infusion + Chemotherapy

Eligibility Criteria

• Age: Up to 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \</= 70 years of age.
• Patients with diagnosis of CML in first chronic phase or accelerated phase with less than 15% blast in the blood and bone marrow at study entry which has failed to respond adequately to imatinib by the consensus criteria of Baccarani et al: a) no hematologic remission at 3 months, b) no cytogenetic response at 6 months, c) no major cytogenetic response at 12 months, d) no complete cytogenetic response or major molecular response at \>18 months, or e) loss of a response with increasing cytogenetic or molecular evidence of disease. Or are intolerant to tyrosine kinase inhibitor therapy. Or with second or greater chronic phase (with prior transformation who respond to treatment and have \<15% blasts at study entry).
• Histocompatible stem cell donor: Patients must have an HLA matched related or unrelated donor (HLA A, B, C and DR) willing to donate for allogeneic hematopoietic transplantation.
• Haploidentical NK cell donor: Patients must have a haploidentical relative with the absence of a KIR-ligand (HLA molecule).
• Performance status: Zubrod \</= 2 or Lansky PS greater or equal to 70%.
• Cardiac function: left ventricular ejection fraction \>/= 40%. No uncontrolled arrhythmias or uncontrolled symptomatic cardiac disease.
• Pulmonary function: no symptomatic pulmonary disease. forced expiratory volume at one second (FEV1), forced vital capacity (FVC) and diffusion capacity of lung for carbon monoxide (DLCO) \>/= 50% of expected, corrected for hemoglobin. For pediatric patients, if unable to perform pulmonary function tests (most children \< 7 years of age), pulse oximetry \>/= 92% on room air by pulse oximetry.
• Renal function: Serum creatinine \</= 1.8mg/dl or creatinine clearance greater or equal than 40 cc/min. Creatinine for pediatric patients \</= 1.5 mg/dl or \</= 2 times upper limit of normal for age (whichever is less).
• Liver function: Bilirubin \</= 1.5 mg/dl (unless Gilbert's syndrome), ALT or AST \</= 200 IU/ml for adults unless related to underline disease. For pediatric patients conjugated (direct) bilirubin \<2x upper limit of normal, ALT or AST \<5 times upper limit of normal.No evidence of chronic active hepatitis or cirrhosis. If positive hepatitis serology, discuss with Study Chairman and consider liver biopsy.
• Patient or patient's legal representative, parent(s) or guardian able to provide written informed consent. Assent as is age appropriate.

You may not qualify if:

• Uncontrolled infection, not responding to appropriate antimicrobial agents after seven days of therapy. The Protocol PI is the final arbiter of eligibility.
• Pleural/pericardial effusion or ascites estimated to be \>1L
• HIV-positive.
• Breast feeding or pregnancy. Pregnancy means a positive beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization.
• Known allergy to mouse proteins
• Active hepatitis B or C infection.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Graft vs Host Disease

Interventions

fludarabine; fludarabine phosphate; Busulfan; Interleukin-2; aldesleukin; Antilymphocyte Serum; thymoglobulin; Tacrolimus; Methotrexate; Granulocyte Colony-Stimulating Factor; Filgrastim

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Macrolides; Lactones; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors

Results Point of Contact

• Title: Richard E. Champlin, MD/Chair, Stem Cell Transplantation
• Organization: University of Texas (UT) MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

Study Officials

• Richard E. Champlin, MD,BS

  M.D. Anderson Cancer Center

  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: July 7, 2011
• First Posted: July 11, 2011
• Study Start: January 1, 2012
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: February 3, 2016
• Results First Posted: December 31, 2015

Record last verified: 2016-01

Locations

US (1)