Imatinib Mesylate, Busulfan, Fludarabine, and Antithymocyte Globulin for CML Patients
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.
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.
|Leukemia||Drug: Imatinib Mesylate Drug: Fludarabine (Fludara) Drug: Busulfan Drug: Antithymocyte Globulin (ATG) Drug: Tacrolimus Drug: Methotrexate Procedure: Donor lymphocyte infusion (DLI) Procedure: Stem Cell Transplant||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Imatinib Mesylate, Busulfan, Fludarabine, Antithymocyte Globulin and Allogeneic Stem Cell Transplantation for Chronic Myelogenous Leukemia|
- Number of Participants in Complete Molecular Remission at 1 Year [ Time Frame: Baseline to 1 year ]Participants at 1 year in molecular remission, post transplant, post imatinib mesylate and donor lymphocyte infusion (DLI). Molecular remission is a complete remission with no evidence of disease in the blood cells and/or bone marrow using sensitive polymerase chain reaction (PCR) tests (this test is most commonly used in clinical trials).
- Participants' With mCR Response to Post Transplant Imatinib Mesylate Therapy [ Time Frame: 1 Year ]Number of participants with response of molecular complete remission (mCR) to Imatinib Mesylate therapy as treatment for residual disease after transplant. Molecular remission is a complete remission with no evidence of disease in the blood cells and/or bone marrow using sensitive polymerase chain reaction (PCR) tests.
- Participants' With mCR Response to Post Transplant DLI [ Time Frame: 1 year ]Number of participants with response of molecular complete remission (mCR) to DLI as treatment for residual disease after transplant. Molecular remission is a complete remission with no evidence of disease in the blood cells and/or bone marrow using sensitive polymerase chain reaction (PCR) tests.
|Study Start Date:||February 2003|
|Study Completion Date:||November 2009|
|Primary Completion Date:||November 2009 (Final data collection date for primary outcome measure)|
Experimental: Imatinib, Busulfan, Fludara + Antithymocyte Globulin
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.
Drug: Imatinib Mesylate
400 mg by mouth twice daily for 9 Days
Other Names:Drug: Fludarabine (Fludara)
40 mg/m^2 by vein daily for 4 Days
Other Names:Drug: Busulfan
130 mg/m^2 by vein daily for 2 Days
Other Names:Drug: Antithymocyte Globulin (ATG)
2.5 mg/kg by vein daily for 3 Days
Other Names:Drug: Tacrolimus
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.
Other Name: PrografDrug: Methotrexate
5 mg/m2 on days 1, 3, 6 and 11.Procedure: Donor lymphocyte infusion (DLI)
Infusion of lymphocytes from the original bone marrow donor by vein if relapse after >4 weeks of imatinib.
Other Names:Procedure: Stem Cell Transplant
Infusion of donor bone marrow or blood stem cells by vein over approximately one hour on day 0.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00499889
|United States, Texas|
|UT MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Richard E. Champlin, MD||M.D. Anderson Cancer Center|