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Allogeneic Stem Cell Transplantation for Myelofibrosis

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00475020
First received: May 15, 2007
Last updated: September 3, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Myelofibrosis
Drug: Busulfan
Drug: Fludarabine
Drug: Thymoglobulin (ATG)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Allogeneic Stem Cell Transplantation for Myelofibrosis Using Reduced Intensity Busulfan and Fludarabine Conditioning

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Rate of Non-Relapse Mortality (NRM) [ Time Frame: 100 Days ] [ Designated as safety issue: Yes ]
    Non-relapse mortality defined as any death not attributable to disease recurrence.


Estimated Enrollment: 110
Study Start Date: January 2006
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: 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
Other Names:
  • Busulfex
  • Myleran
Drug: Fludarabine
40 mg/m^2 by vein daily over 1 hour x 4 days
Other Name: Fludarabine Phosphate
Drug: Thymoglobulin (ATG)
2.5 mg/kg by vein over 6 hours x 3 days if there is an unrelated or a mismatched donor
Other Names:
  • Antithymocyte Globulin
  • Thymoglobulin
  • ATG

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

Ages Eligible for Study:   up to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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), SGPT </= 4 x normal values
  8. FEV1, FVC, or DLCO >/= 40% of expected.
  9. Negative Beta 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00475020

Locations
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Uday Popat, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00475020     History of Changes
Other Study ID Numbers: 2005-0726, NCI-2012-01477
Study First Received: May 15, 2007
Last Updated: September 3, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Idiopathic Myelofibrosis
Myelofibrosis
Essential Thrombocythemia
Polycythemia Vera
Busulfan
Antithymocyte Globulin
ATG
Fludarabine
Thymoglobulin

Additional relevant MeSH terms:
Primary Myelofibrosis
Bone Marrow Diseases
Hematologic Diseases
Myeloproliferative Disorders
Antilymphocyte Serum
Busulfan
Fludarabine
Fludarabine phosphate
Vidarabine
Alkylating Agents
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antiviral Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014