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Fludarabine, Campath, TBI T-Cell Deplete NMSCT With Post-Transplant T-Cell Infusions for CML Failing Imatinib Therapy With Imatinib (STI571)

Phase 2
4 Years
75 Years
Not Enrolling

Thank you

Trial Information

Fludarabine, Campath, TBI T-Cell Deplete NMSCT With Post-Transplant T-Cell Infusions for CML Failing Imatinib Therapy With Imatinib (STI571)


- Determine the treatment-related mortality in patients with imatinib mesylate-resistant
chronic phase chronic myelogenous leukemia treated with nonmyeloablative conditioning
comprising fludarabine, alemtuzumab, and total-body irradiation followed by
T-cell-depleted allogeneic stem cell transplantation and post-transplantation
allogeneic T-cell infusion.

- Determine if donor engraftment can be safely established using partial T-cell depletion
with additional T-cell infusions in these patients.

OUTLINE: Patients receive alemtuzumab IV over 5-6 hours on day -8 and fludarabine IV on days
-4 to -2. Patients undergo total-body irradiation followed by T-cell-depleted (CD34+
selected) allogeneic stem cell transplantation on day 0. Patients receive allogeneic T-cell
infusion on days 30 and 60. Patients also receive cyclosporine twice daily beginning on day
-3 and continuing until day 100 followed by a taper until day 177.


Inclusion Criteria

Inclusion criteria:

- 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.

Exclusion criteria:

- Patients who have received another investigational drug within 30 days.

- Fertile men unwilling to use contraceptive techniques during and for 24 months
following treatment.

- 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
potentially unreliable.

- 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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Participants With Treatment-related Mortality

Outcome Description:

Treatment related mortality is a consequence of both complications of the preparative regimen and systemic immunological rejection which is manifested as graft versus host disease(GVHD). The preparative regimens which include whole body radiation and/or high dose chemotherapy are complicated by single or multi-organ failure and by prolonged myelosuppression that can lead to infections and bleeding

Outcome Time Frame:

lifetime followup, up to 100 years.

Safety Issue:


Principal Investigator

Richard Maziarz, MD

Investigator Role:

Study Chair

Investigator Affiliation:

OHSU Knight Cancer Institute


United States: Federal Government

Study ID:




Start Date:

May 2003

Completion Date:

March 2008

Related Keywords:

  • Leukemia
  • chronic phase chronic myelogenous leukemia
  • childhood chronic myelogenous leukemia
  • relapsing chronic myelogenous leukemia
  • Leukemia



OHSU Knight Cancer Institute Portland, Oregon  97239