Allogeneic Stem Cell Transplantation for Myelofibrosis and Myelodysplastic Syndrome Using Reduced Intensity Busulfan and Fludarabine Conditioning
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 63
- Locations
- 1
- Primary Endpoint
- Rate of Non-relapse Mortality at 100 Days Post-transplant
Study Overview
Brief Summary
The goal of this clinical research study is to learn if using a combination of fludarabine, busulfan, and antithymocyte globulin (ATG) can help to control myelofibrosis or myelodysplastic syndrome in patients receiving a bone marrow or blood stem cell transplant. The safety of these drugs will also be studied.
Detailed Description
Busulfan is a chemotherapy drug that kills cancer cells by binding to DNA, and is commonly used in stem cell transplants. Fludarabine is a drug that has anti-leukemia and immunosuppressive effects. ATG helps to reduce the risk of transplant rejection and to prevent graft versus host disease.
You will receive fludarabine by vein over 1 hour on Days -5 to -2. You will receive busulfan by vein over 3 hours on Day -5 to -2 immediately after completing fludarabine. If you have an unrelated or a mismatched donor, you will receive ATG by vein over 6 hours on Days -3 to -1 to prevent graft versus host disease and to help engraftment.
You will first receive a low-level "test" dose of busulfan, and blood samples (about 1 teaspoon each time) will be drawn for pharmacokinetic (PK) tests. This may be done as an outpatient prior to inpatient admission. PK tests measure the level of the study drug in the blood over different time points. This information will be used to decide the next dose needed to reach the target blood level that matches your body size.
About 11 total samples of blood will be drawn for PK testing after the test dose and before the first high-dose busulfan treatment. A heparin lock will be placed in your vein to lower the number of needle sticks needed for these draws. If it is not possible for these blood level tests to be performed for technical or scheduling reasons or for any other reason, you will receive the standard fixed busulfan dose without the "test dose."
You will receive the donor bone marrow or blood stem cells by vein over about 1 hour on Day 0.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- — to 75 Years (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients with Idiopathic Myelofibrosis or Myelofibrosis secondary to Polycythemia Vera or Essential Thrombocythemia or Myelodysplastic syndrome with or without fibrosis.
- •Patients 75 years or younger
- •Patients must have an HLA matched or at least a 9/10 antigen (A, B, C, DQ or DR) matched related or unrelated donor.
- •Patients must have a Zubrod PS 2 or less.
- •Creatinine < 1.6 mg/dl
- •Ejection fraction >/= 40%, unless cleared by cardiology
- •Serum direct bilirubin < 2 mg/dl (unless due to Gilbert's syndrome), serum glutamate pyruvate transaminase (SGPT) </= 4 x normal values
- •Forced expiratory volume at one second (FEV1), forced vital capacity (FVC), or diffusing capacity of lung for carbon monoxide (DLCO) >/= 40% of expected.
- •Negative Beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization.
Exclusion Criteria
- •Uncontrolled life-threatening infections
- •HIV positive
- •Patients with Active viral hepatitis
Arms & Interventions
Fludarabine + Busulfan + Thymoglobulin
Fludarabine 40 mg/m^2 by vein daily over 1 hour x 4 days. Busulfan test dose = 32 mg/m^2 by vein x 1 day; 100 mg/m^2 by vein daily over 3 hours x 4 days. Thymoglobulin 2.5 mg/kg by vein over 6 hours x 3 days if there is an unrelated or a mismatched donor.
Intervention: Busulfan (Drug)
Fludarabine + Busulfan + Thymoglobulin
Fludarabine 40 mg/m^2 by vein daily over 1 hour x 4 days. Busulfan test dose = 32 mg/m^2 by vein x 1 day; 100 mg/m^2 by vein daily over 3 hours x 4 days. Thymoglobulin 2.5 mg/kg by vein over 6 hours x 3 days if there is an unrelated or a mismatched donor.
Intervention: Fludarabine (Drug)
Fludarabine + Busulfan + Thymoglobulin
Fludarabine 40 mg/m^2 by vein daily over 1 hour x 4 days. Busulfan test dose = 32 mg/m^2 by vein x 1 day; 100 mg/m^2 by vein daily over 3 hours x 4 days. Thymoglobulin 2.5 mg/kg by vein over 6 hours x 3 days if there is an unrelated or a mismatched donor.
Intervention: Thymoglobulin (ATG) (Drug)
Outcomes
Primary Outcomes
Rate of Non-relapse Mortality at 100 Days Post-transplant
Time Frame: Non-relapse mortality at 100 days post-transplant
To evaluate the safety of Fludarabine/Busulfan as conditioned regimen for allogeneic stem cell transplantation in patients with myelofibrosis/myelodysplastic syndrome at 100 days post-transplant
Secondary Outcomes
- Efficacy of This Therapy 3 Years Post-transplant(Up to 3 years post-transplant)