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| Sponsor: | M.D. Anderson Cancer Center |
|---|---|
| Information provided by: | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT00038831 |
Purpose
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.
Primary Objective:
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.
Secondary Objectives:
| Condition | Intervention | Phase |
|---|---|---|
|
Acute Myelogenous Leukemia Myelodysplastic Syndrome Chronic Lymphocytic Leukemia |
Drug: Mylotarg Drug: Fludarabine Drug: Melphalan Drug: Anti-thymocyte globulin Procedure: Stem cell transplant |
Phase I Phase II |
| Study Type: | Interventional |
| Study Design: | Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study |
| 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 |
| Enrollment: | 47 |
| Study Start Date: | May 2001 |
| Study Completion Date: | October 2006 |
| Primary Completion Date: | March 2005 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Chemotherapy + ATG + Stem Cell Infusion: Experimental |
Drug: Mylotarg
Starting dose 2 mg/m^2 over 2-hour intravenous infusion on day -12.
Drug: Fludarabine
30 mg/m^2 will be given intravenously daily at the same time over 30 minutes on days -5, -4, -3, -2.
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.
Drug: 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.
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.
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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.
Eligibility| Ages Eligible for Study: | 12 Years to 75 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Patients with the following disease categories will be eligible:
Exclusion Criteria:
Contacts and Locations| United States, Texas | |
| MD Anderson Cancer Center | |
| Houston, Texas, United States, 77030 | |
| Principal Investigator: | Marcos De Lima, MD | U.T. M.D. Anderson Cancer Center |
More Information
| Responsible Party: | UT MD Anderson Cancer Center ( Marcos de Lima, MD / Associate Professor ) |
| Study ID Numbers: | ID01-010 |
| Study First Received: | June 5, 2002 |
| Last Updated: | October 22, 2009 |
| ClinicalTrials.gov Identifier: | NCT00038831 History of Changes |
| Health Authority: | United States: Food and Drug Administration |
|
Acute Myelogenous leukemia AML Myelodysplastic Syndrome MDS Chronic Lymphocytic Leukemia CML Mylotarg Gemtuzumab Gemtuzumab ozogamicin Melphalan |
Alkeran Fludarabine Phosphate Fludarabine Fludara Anti-thymocyte globulin ATG Allogeneic Bone Marrow Peripheral Blood Stem Cell Transplantation Allo PBSCT Allogeneic transplantation |
|
Antimetabolites Anti-Infective Agents Melphalan Vidarabine Leukemia, Lymphoid Antimetabolites, Antineoplastic Molecular Mechanisms of Pharmacological Action Immunologic Factors Precancerous Conditions Antineoplastic Agents Physiological Effects of Drugs Leukemia, Myeloid, Acute Antibodies, Monoclonal Leukemia Preleukemia |
Pathologic Processes Leukemia, Lymphocytic, Chronic, B-Cell Therapeutic Uses Syndrome Alkylating Agents Neoplasms by Histologic Type Immunoproliferative Disorders Disease Immune System Diseases Hematologic Diseases Myelodysplastic Syndromes Leukemia, Myeloid Fludarabine monophosphate Gemtuzumab Antiviral Agents |