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URL http://www.rockymountainbmt.com/clinical_trials/1581---Allogeneic-Nonmyeloablative-Hematopoietic-Stem-Cell-Transplant-for-Patients-with-STI-571-Responsive-Ph-Acute-Leukemia---Multi-Center-Trial-19.html

1581 - Allogeneic Nonmyeloablative Hematopoietic Stem Cell Transplant for Patients with STI-571 Responsive Ph+ Acute Leukemia - Multi-Center Trial

Principal Investigator: Michael B. Maris, MD

Protocol Number: RMBMT 151

Major Objectives

1. To determine whether the rate of leukemia relapse can be decreased for patients with CML-BC and Ph+ ALL responsive to STI-571 followed by nonmyeloablative HSCT compared to historical controls given high-dose conventional allogeneic HSCT or chemotherapy.
2. To determine whether the rate of TRM can be decreased for patients with CML-BC and Ph+ ALL responsive to STI-571 followed by nonmyeloablative HSCT compared to historical controls given high-dose conventional allogeneic HSCT or chemotherapy.

Minor Objectives

1. To evaluate whether DLI can be safely used in patients with mixed or full donor chimerism as preemptive therapy to eliminate minimal residual disease. .

Patient Selection

Inclusion Criteria:

1. Patients ≤ 70 years of age. Patients ≤ 12 years of age must be approved by FHCRC PI in advance.
2. Patients with a history of Ph+ ALL or CML-BC who, after receiving STI-571, have <15% blasts on morphologic marrow evaluation. Patients with no detectable Ph+ ALL by morphologic or molecular assays (complete remission) will be accepted.
3. An appropriately HLA matched related or unrelated donor (see donor selection criteria) must be prospectively identified who will be available to donate G-CSF mobilized stem cells.

Exclusion Criteria:

1. CNS involvement with leukemia refractory to intrathecal chemotherapy.
2. Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment.
3. Females who are pregnant.
4. Patients who are HIV positive.
5. Patients with poorly controlled hypertension despite multiple antihypertensives
6. Karnofsky score < 60
7. Organ dysfunction:
   1. Cardiac: Patients with Grade 4 cardiac disease OR cardiac ejection fraction < 35%. Ejection fraction is required if there is a history of anthracycline exposure or history of cardiac disease.
   2. Pulmonary: DLCO < 40% and/or requiring continuous supplementary oxygen.
   3. Hepatic: Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension. Patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin >3 mg/dL, and symptomatic biliary disease.
   4. Renal: Creatinine levels more than 2.0 x’s the ULN at the laboratory where the analysis was performed.

Donor Selection

Inclusion Criteria:

1. Related donor who is HLA genotypically identical at least at one haplotype and may be genotypically or phenotypically identical at the allele level at HLA-A, -B, -C, -DRB1, and –DQB1.
2. Related donor
   1. Donor must consent to G-CSF administration and leukapheresis.
   2. Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian).

1. Related or unrelated donors who are matched for HLA-DRB1 and DQB1 alleles (must be defined by high resolution typing), and who are matched for:
   1. Matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing;
   2. Only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing
2. PBSC only will be permitted as a stem cell source on this protocol.

Exclusion Criteria:

1. Identical twin.
2. Infection with HIV.
3. Inability to achieve adequate venous access.
4. Known allergy to G-CSF.
5. Current serious systemic illness.
6. BM donors

1. BM donors
2. Donors who are HIV-positive and/or, medical conditions that would result in increased risk for G-CSF mobilization and harvest of PBSC