Allo Transplantation With Mylotarg, Fludarabine and Melphalan for AML, CML and MDS
The goal of this clinical research study is to find the highest safe dose of Mylotarg that can be combined with chemotherapy in patients receiving allogeneic bone marrow transplantation. Researchers will study the effects of this treatment combination on patients with high-risk acute leukemia, chronic myelogenous leukemia, or myelodysplastic syndrome.
1. To determine the safety and maximum tolerated dose of Mylotarg as part of a reduced-intensity preparative regimen patients undergoing related, mismatched-related or matched unrelated donor transplantation.
- To evaluate response rates, engraftment kinetics and degree of chimerism achievable with this strategy.
- To evaluate the incidence and severity of GVHD in this population
- To evaluate disease-free and overall survival and relapse rates.
|Acute Myelogenous Leukemia Myelodysplastic Syndrome Chronic Lymphocytic Leukemia||Drug: Mylotarg Drug: Fludarabine Drug: Melphalan Drug: Anti-thymocyte globulin Procedure: Stem cell transplant||Phase 1 Phase 2|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Evaluation of Safety and Activity of Mylotarg Plus Melphalan and Fludarabine as Preparative Therapy for Older or Medically Infirm Patients Undergoing Allogeneic Bone Marrow and Peripheral Blood Stem Cell Transplantation|
- Maximum Tolerated Dose (MTD) of Mylotarg as Determined by Number of Participants With Dose Limiting Toxicity (DLT) at Each Dose Level [ Time Frame: Followed in outpatient clinic from day -12 (prior to transplant) thru day -6 with each dose level ]
- Patient Response [ Time Frame: Continously over first 30 days ]
|Study Start Date:||May 2001|
|Study Completion Date:||October 2006|
|Primary Completion Date:||March 2005 (Final data collection date for primary outcome measure)|
|Experimental: Chemotherapy + ATG + Stem Cell Infusion||
Starting dose 2 mg/m^2 over 2-hour intravenous infusion on day -12.
Other Names:Drug: Fludarabine
30 mg/m^2 will be given intravenously daily at the same time over 30 minutes on days -5, -4, -3, -2.
Other Names:Drug: Melphalan
140 mg/m^2 will be given intravenously over 20 minutes starting 2 hours after the beginning of the fludarabine infusion on day -2.
Other Name: AlkeranDrug: Anti-thymocyte globulin
Patients with an unrelated or mismatched related donor will receive 0.5 mg/kg on day -3 and 1.25 mg/Kg on days -2 and -1, following the chemotherapy.
Other Names:Procedure: Stem cell transplant
Allogeneic Bone Marrow and Peripheral Blood Stem Cell Transplantation: Infusion of blood stem cells or bone marrow cells on day 0.
Before treatment starts, patients will have a complete physical exam, including blood and urine tests. Patients will have a chest x-ray, heart scan, lung function test, and a bone marrow biopsy. Women who are able to have children will have a pregnancy test.
In this study, patients will receive Mylotarg twelve days before the transplant. The first patients will receive Mylotarg at the lowest dose level. As the study continues, the dose levels will be increased as long as no severe side effects occur. Mylotarg may be given in the outpatient Ambulatory Treatment Center (ATC). Patients will be monitored in the ATC for eight hours on the day of infusion. For the next 5 days, patients will be evaluated in the Clinic on a daily basis or as per physician orders. One week before the transplant, all patients will be admitted to the hospital and will continue their treatment as inpatients. Patients experiencing side effects from their leukemia or leukemia treatment may need to be hospitalized earlier.
On the 1st day of hospitalization, patients will receive fluids by vein. On the 5th, 4th, 3rd and 2nd day before the transplant, patients will receive Fludarabine, by vein. Melphalan will be given by vein on the 2nd day before transplant. Patients receiving five out of six antigen matched or unrelated bone marrow will also receive antithymocyte globulin, by vein, on the 3rd, 2nd and 1st day before transplant.
On the 7th day, healthy blood stem cells or bone marrow from the donor will be given through the central catheter. Some donor bone marrow or stem cells may be saved for future therapies.
Patients will also receive several other medications to help the treatment work and to help prevent infections while their immune system is weak. Tacrolimus and methotrexate will be given to prevent graft-versus-host disease (GVHD). GVHD occurs when the donor's immune cells fight the patient's body. The Tacrolimus will be started on the day before the transplant and will continue for up to six months. Tacrolimus is given by vein at first and then by mouth when patients are able to eat. Methotrexate is given by vein on days 1, 3, 6 and possibly on day 11 after the transplant.
Sulfamethoxazole (Bactrim) or pentamidine will be given to fight bacteria. Bactrim is given by mouth when the counts are good. Pentamidine is given by vein when the counts are low. Acyclovir will be given at first by vein and then Valtrex will be given by pill to prevent viral infections. Granulocyte colony-stimulating factor (G-CSF) will be given to help the new bone marrow grow. It is given as an injection under the skin beginning on the 7th day after the transplant. It will continue until the patient's white blood cells reach an acceptable level. Overall, some of these drugs will be given for as long as 6 months or possibly longer. Other medications may be necessary. If you are allergic to some of these drugs, changes will be made.
Patients will be in the hospital for about 3-4 weeks. Patients will have checkups every day until discharged from the hospital then 3 times a week until their blood counts improve. Patients will then be seen by their doctor at least every week until 100 days after the bone marrow transplant. Patients must stay in Houston during this time. After 100 days, patients will return at least every 3 months for the first year, then every 6 months for an additional two years.
Bone marrow samples will be taken at about 1 month, 3 months, 6 and 12 months after the transplant.
This is an investigational study. All of the drugs in this study are approved by the FDA. About 47 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: NCT00038831
|United States, Texas|
|MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Marcos De Lima, MD||M.D. Anderson Cancer Center|