Clinical trial NCT00499889
Conditions: Leukemia
Keywords: Chronic Myelogenous Leukemia Allogeneic Stem Cell Transplantation Leukemia Imatinib Mesylate Gleevec Busulfan Busulfex Myleran Fludarabine ATG STI571 Antithymocyte Globulin Thymoglobulin
Sponsor: M.D. Anderson Cancer Center
Start date: 2003-02-01; Completion date: 2009-11-01
Enrollment: 42 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Primary Objective:

To estimate the probability of molecular complete remission at one year for the described sequential treatment approach, with nonablative hematopoietic transplantation, post transplant imatinib mesylate and donor lymphocyte infusion, in patients with Ph-positive Chronic Myelogenous Leukemia (CML) not in blastic transformation.

Secondary Objective:

Response to post transplant Imatinib mesylate therapy for 12 weeks as treatment of residual disease, response to donor lymphocyte infusion (DLI) for residual disease following imatinib mesylate therapy, as well as engraftment, toxicity, disease free survival and survival, effect of busulfan pharmacokinetics on study outcome.

Detailed description:
Patients will have blood and bone marrow tests performed as well as chest and sinus X-rays and tests of their heart and lung function. Approximately 5 tablespoons of blood will be drawn.

All patients in this study will receive imatinib mesylate by mouth for 9 days, unless the patient is known to be allergic or have symptomatic intolerance to the drug, or if the leukemia has failed to respond to imatinib. Fludarabine 40 mg/m2 by vein for 4 days (days -5 to -2), busulfan 130 mg/m2 by vein for 2 days (days -3 and -2), and ATG (Antithymocyte Globulin) 2.5 mg/kg by vein for 3 days (-3,-2 and -1).

Patients will then receive the donor bone marrow or blood stem cells by vein over approximately one hour on day 0.

After the infusion of the donor cells, you will receive immunosuppressive therapy with tacrolimus and methotrexate to decrease the risk of developing graft-vs-host disease (GvHD).

Patients will need frequent blood tests to monitor their counts and blood chemistries. This is generally done daily while in hospital and at least twice per week for the first 100 days post transplant. You may need frequent blood transfusions and may have to be admitted to the hospital to receive antibiotics if they develop fever. Bone marrow will be examined frequently beginning four weeks after treatment to evaluate response to treatment; Blood and bone marrow exams are to be performed at one, two three, six, 12 and 18 months post transplant and yearly thereafter for 5 years. To collect a bone marrow sample, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle.

Patients in whom treatment produces a remission, in which no sign of the leukemia can be detected, will receive no further therapy unless the leukemia recurs. Patients with evidence of leukemia after 3 months from the transplant will receive additional treatment with imatinib mesylate; those with detectable leukemia after an additional 3 months may receive an infusion of immune cells from the transplant donor.

If there is evidence of leukemia after the transplant, you will receive additional treatment with imatinib mesylate. If leukemia cells can still be detected, additional donor immune cells will be given to you by vein.

Patients are considered on the study for 5 years after the transplant.

A total of 90 patients will take part in this study. All will be enrolled at M. D. Anderson.

Arms: arm 1: Oral Imatinib Mesylate 400 mg twice a day for 9 Days; Busulfan 130 mg/m\^2 by vein (IV) daily for 2 Days; Fludara 40 mg/m\^2 IV daily for 4 Days; Antithymocyte Globulin (ATG) 2.5 mg/kg IV daily for 3 Days; Tacrolimus levels maintained between 5-15 ng/dl, Day -2 to Day 180; Methotrexate 5 mg/m2 on days 1, 3, 6 and 11; and Donor bone marrow or blood stem cells infused on day 0 with possible donor lymphocyte infusion (DLI) for progressive disease.
Interventions: intervention 1: Imatinib Mesylate intervention 2: Fludarabine (Fludara) intervention 3: Busulfan intervention 4: Antithymocyte Globulin (ATG) intervention 5: Tacrolimus intervention 6: Methotrexate intervention 7: Donor lymphocyte infusion (DLI) intervention 8: Stem Cell Transplant
Intervention descriptions: intervention 1: 400 mg by mouth twice daily for 9 Days intervention 2: 40 mg/m\^2 by vein daily for 4 Days intervention 3: 130 mg/m\^2 by vein daily for 2 Days intervention 4: 2.5 mg/kg by vein daily for 3 Days intervention 5: Tacrolimus levels maintained between 5-15 ng/dl, first as continuous IV infusion, and converted to oral every 12 hour dosing as tolerated. Starting day -2 until day 180. intervention 6: 5 mg/m2 on days 1, 3, 6 and 11. intervention 7: Infusion of lymphocytes from the original bone marrow donor by vein if relapse after \>4 weeks of imatinib. intervention 8: Infusion of donor bone marrow or blood stem cells by vein over approximately one hour on day 0.

Protocol documents: