Fludarabine, Campath, TBI T-Cell Deplete NMSCT With Post-Transplant T-Cell Infusions for CML Failing Imatinib Therapy With Imatinib (STI571)
- Patients aged 4-75 with chronic myelogenous leukemia (CML) treatable by allogeneic
hematopoietic stem cell transplant.
- Patients with cytogenetically confirmed chronic phase CML.
o Hematologic parameters for chronic phase are:
i) Percentage of blasts in peripheral blood or
marrow < 15% ii) Percentage of blasts + promyelocytes in the
peripheral blood or bone marrow < 30% iii) Percentage of basophils in blood or
marrow <20% iv) Platelet count > 100 x 109/l
- Patients must have demonstrated refractoriness/resistance to STI571 defined as
i) Hematologically resistant- failure to achieve a complete hematologic remission
(CHR) despite 3 months of STI571 therapy.
ii) Hematologically refractory - a rising WBC count > 20 x 109/l confirmed by two samples
taken two weeks apart in a patient with a previous CHR despite concurrent treatment with
STI571 iii) Cytogenetically resistant - bone marrow cytogenetics showing > 65%
Philadelphia chromosome positivity (Ph+) after 6 months of STI571 based therapy.
iv) Cytogenetically refractory - An increase in the number of Philadelphia chromosome
positive (Ph+) bone marrow cells by at least 30%, or an increase to > 65%, confirmed by
samples at least 1 month apart following a previous STI571 induced cytogenetic
response, while continuing STI571 therapy.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- Patients with a human leukocyte antigen (HLA) matched sibling donor at the HLA-A, B,
and DR loci.
- Patients with an unrelated hematopoietic stem cell donor must be matched using high
resolution typing for class II human leukocyte antigen (HLA-DR beta-1, 3, 4, 5 and DQ
beta-1) and matched with intermediate to high resolution molecular typing at class I
human leukocyte antigen (HLA-A, B, and C) loci.
- Patients with accelerated or blast crisis of CML who have returned to chronic phase
as described above are eligible.
- Written informed, voluntary consent.
- Patients who have received another investigational drug within 30 days.
- Fertile men unwilling to use contraceptive techniques during and for 24 months
- Females who are pregnant or fertile women unwilling to use contraceptive techniques
for two months prior to entering the study and for 24 months following treatment.
- Patients with active bacterial or fungal infections unresponsive to medical therapy.
- Patients with organ dysfunction including cardiac ejection fraction of less than 35%
or pulmonary status with a diffusing capacity of the lung for carbon monoxide(DLCO)
of less than 40% and/or receiving supplemental oxygen.
- Liver Function Abnormalities: patients will be excluded if they are found to have
fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension,
alcoholic hepatitis, varices, history of bleeding varices, hepatic encephalopathy or
chronic viral hepatitis where the total serum bilirubin is greater than 3 mg per
deciliter with symptomatic biliary disease.
- Patients with a history of non-compliance to medical regimens or who are considered
- Patients with a history of any prior bone marrow or peripheral blood stem cell
- Patients with any other serious, uncontrolled, concomitant medical condition
- HIV positive patients
Eligibility criteria for donors:
Inclusion Criteria for Donors:
- Sibling donors are permitted if matched at class I human leukocyte antigen (HLA-A,
B), and class II human leukocyte antigen (DR) loci.
- Unrelated donors must be matched for class II human leukocyte antigen(HLA-DR
beta-1,2,3,4,5) and class II human leukocyte antigen (DQ beta-1) with high
resolution typing and with intermediate resolution molecular typing at class I human
leukocyte antigen(HLA-A, B, and C) loci.
- Donors must be eligible to serve as a peripheral stem cell allograft donor. Bone
marrow donors will not be permitted on this protocol.
- Donors must be >18 and < 75 years of age.
Exclusions Criteria for Donors:
- Volunteer donors who wish to serve as bone marrow donors only and refuse exogenous
- Donors who are Human immunodeficiency virus (HIV+), Human T-lymphotropic virus
(HTLV-1+), or hepatitis Bs Ag+..
- Donors with medical conditions that would result in increased risk for Granulocyte
colony-stimulating factor (G-CSF) mobilization and harvest of peripheral blood stem
cells (PBSC) including renal insufficiency with Cr > 2.0, idiopathic splenomegaly,
underlying coagulopathy, uncontrolled coronary artery disease, and major surgery
within 28 days.