Overview

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

Status:
Completed

Trial end date:
2014-11-01

Target enrollment:
0

Participant gender:
All

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.

Phase:

Phase 2

Accepts Healthy Volunteers?

Details

Lead Sponsor:

M.D. Anderson Cancer Center

Collaborator:

National Cancer Institute (NCI)

Treatments:

Aldesleukin
Antilymphocyte Serum
Busulfan
Fludarabine
Fludarabine phosphate
Interleukin-2
Methotrexate
Tacrolimus
Thymoglobulin
Vidarabine

Criteria

Inclusion Criteria:

1. Patients who meet the following eligibility criteria are eligible for inclusion in
this study. Pediatric team to assess eligibility appropriate for patient age.

2. Age
3. 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).

4. 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.

5. Haploidentical NK cell donor: Patients must have a haploidentical relative with the
absence of a KIR-ligand (HLA molecule).

6. Performance status: Zubrod
7. Cardiac function: left ventricular ejection fraction >/= 40%. No uncontrolled
arrhythmias or uncontrolled symptomatic cardiac disease.

8. 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.

9. Renal function: Serum creatinine than 40 cc/min. Creatinine for pediatric patients limit of normal for age (whichever is less).

10. Liver function: Bilirubin 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.

11. Patient or patient's legal representative, parent(s) or guardian able to provide
written informed consent. Assent as is age appropriate.

Exclusion Criteria:

1. Uncontrolled infection, not responding to appropriate antimicrobial agents after seven
days of therapy. The Protocol PI is the final arbiter of eligibility.

2. Pleural/pericardial effusion or ascites estimated to be >1L

3. HIV-positive.

4. 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.

5. Known allergy to mouse proteins

6. Active hepatitis B or C infection.