Clinical trial NCT00475020: Allogeneic Stem Cell Transplantation for Myelofibrosis and Myelodysplastic Syndrome
Official title: Allogeneic Stem Cell Transplantation for Myelofibrosis and Myelodysplastic Syndrome Using Reduced Intensity Busulfan and Fludarabine Conditioning
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myelofibrosis
Keywords: Idiopathic Myelofibrosis
Myelofibrosis
Essential Thrombocythemia
Polycythemia Vera
Busulfan
Antithymocyte Globulin
ATG
Fludarabine
Thymoglobulin
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
First posted: 2007-05-17
Enrollment: 63
Sex: ALL
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Two (2) days before the stem cell infusion on Day -2, tacrolimus will be started as a non-stop infusion by vein and will be changed to oral tablets before you leave the hospital. You will continue to take tacrolimus by mouth, for at least 4 months.

Four (4) doses of Methotrexate will be give as a short infusion Day 1, Day 3, Day 6 and Day 11 after stem cell infusion. Both these are given to decrease the risk of getting graft-vs-host disease (GvHD). Further immunosuppressive therapy with methylprednisolone (a steroid) or other drugs may also be used to treat GvHD if it occurs.

You will have 3 teaspoonfuls of blood drawn for routine tests every day while you are in the hospital and at least 2 times a week for the first 100 days after transplant. You may need frequent blood transfusions and may have to be admitted to the hospital to receive antibiotics if you get a fever. Three (3) teaspoonful of blood and a bone marrow aspirate and biopsy will be taken 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months after the transplant to check the response to the treatment. After the first 2 years, your disease status will be followed by a yearly phone call or letter from you or your regular doctor to the study doctor.

Tests and/or procedures may be performed before the scheduled time, if your doctor thinks it is needed.

You will be taken off the study if your disease gets worse or if further treatment is not in your best interest.

This is an investigational study. All the drugs to be used in this study are FDA approved and commercially available. About 110 patients will take part in this study. All will be enrolled at MD Anderson.

Eligibility criteria: Inclusion Criteria:

1. Patients with Idiopathic Myelofibrosis or Myelofibrosis secondary to Polycythemia Vera or Essential Thrombocythemia or Myelodysplastic syndrome with or without fibrosis.
2. Patients 75 years or younger
3. Patients must have an HLA matched or at least a 9/10 antigen (A, B, C, DQ or DR) matched related or unrelated donor.
4. Patients must have a Zubrod PS 2 or less.
5. Creatinine \< 1.6 mg/dl
6. Ejection fraction \>/= 40%, unless cleared by cardiology
7. Serum direct bilirubin \< 2 mg/dl (unless due to Gilbert's syndrome), serum glutamate pyruvate transaminase (SGPT) \</= 4 x normal values
8. Forced expiratory volume at one second (FEV1), forced vital capacity (FVC), or diffusing capacity of lung for carbon monoxide (DLCO) \>/= 40% of expected.
9. 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:

1. Uncontrolled life-threatening infections
2. HIV positive
3. Patients with Active viral hepatitis

Primary outcomes:
measure: Rate of Non-relapse Mortality at 100 Days Post-transplant
timeFrame: Non-relapse mortality at 100 days post-transplant
Secondary outcomes:
measure: Efficacy of This Therapy 3 Years Post-transplant
timeFrame: Up to 3 years post-transplant
Other outcomes:
Locations:
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Uday Popat, MD
role: PRINCIPAL_INVESTIGATOR
References: