Imatinib Mesylate, Busulfan, Fludarabine, and Antithymocyte Globulin for CML Patients

This study has been terminated.
(Support issue.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00499889
First received: July 10, 2007
Last updated: April 19, 2012
Last verified: April 2012
  Purpose

Primary Objective:

To estimate the probability of molecular complete remission at one year for the described sequential treatment approach, with nonablative hematopoietic transplantation, post transplant imatinib mesylate and donor lymphocyte infusion, in patients with Ph-positive Chronic Myelogenous Leukemia (CML) not in blastic transformation.

Secondary Objective:

Response to post transplant Imatinib mesylate therapy for 12 weeks as treatment of residual disease, response to donor lymphocyte infusion (DLI) for residual disease following imatinib mesylate therapy, as well as engraftment, toxicity, disease free survival and survival, effect of busulfan pharmacokinetics on study outcome.


Condition Intervention Phase
Leukemia
Drug: Imatinib Mesylate
Drug: Fludarabine (Fludara)
Drug: Busulfan
Drug: Antithymocyte Globulin (ATG)
Drug: Tacrolimus
Drug: Methotrexate
Procedure: Donor lymphocyte infusion (DLI)
Procedure: Stem Cell Transplant
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: Imatinib Mesylate, Busulfan, Fludarabine, Antithymocyte Globulin and Allogeneic Stem Cell Transplantation for Chronic Myelogenous Leukemia

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number of Participants in Complete Molecular Remission at 1 Year [ Time Frame: Baseline to 1 year ] [ Designated as safety issue: No ]
    Participants at 1 year in molecular remission, post transplant, post imatinib mesylate and donor lymphocyte infusion (DLI). Molecular remission is a complete remission with no evidence of disease in the blood cells and/or bone marrow using sensitive polymerase chain reaction (PCR) tests (this test is most commonly used in clinical trials).


Secondary Outcome Measures:
  • Participants' With mCR Response to Post Transplant Imatinib Mesylate Therapy [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    Number of participants with response of molecular complete remission (mCR) to Imatinib Mesylate therapy as treatment for residual disease after transplant. Molecular remission is a complete remission with no evidence of disease in the blood cells and/or bone marrow using sensitive polymerase chain reaction (PCR) tests.

  • Participants' With mCR Response to Post Transplant DLI [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Number of participants with response of molecular complete remission (mCR) to DLI as treatment for residual disease after transplant. Molecular remission is a complete remission with no evidence of disease in the blood cells and/or bone marrow using sensitive polymerase chain reaction (PCR) tests.


Enrollment: 42
Study Start Date: February 2003
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Imatinib, Busulfan, Fludara + Antithymocyte Globulin
Oral Imatinib Mesylate 400 mg twice a day for 9 Days; Busulfan 130 mg/m^2 by vein (IV) daily for 2 Days; Fludara 40 mg/m^2 IV daily for 4 Days; Antithymocyte Globulin (ATG) 2.5 mg/kg IV daily for 3 Days; Tacrolimus levels maintained between 5-15 ng/dl, Day -2 to Day 180; Methotrexate 5 mg/m2 on days 1, 3, 6 and 11; and Donor bone marrow or blood stem cells infused on day 0 with possible donor lymphocyte infusion (DLI) for progressive disease.
Drug: Imatinib Mesylate
400 mg by mouth twice daily for 9 Days
Other Names:
  • Gleevec
  • STI571
Drug: Fludarabine (Fludara)
40 mg/m^2 by vein daily for 4 Days
Other Names:
  • Fludarabine Phosphate
  • Fludara
  • Fludarabine
Drug: Busulfan
130 mg/m^2 by vein daily for 2 Days
Other Names:
  • Busulfex
  • Myleran
Drug: Antithymocyte Globulin (ATG)
2.5 mg/kg by vein daily for 3 Days
Other Names:
  • ATG
  • Thymoglobulin
Drug: Tacrolimus
Tacrolimus levels maintained between 5-15 ng/dl, first as continuous IV infusion, and converted to oral every 12 hour dosing as tolerated. Starting day -2 until day 180.
Other Name: Prograf
Drug: Methotrexate
5 mg/m2 on days 1, 3, 6 and 11.
Procedure: Donor lymphocyte infusion (DLI)
Infusion of lymphocytes from the original bone marrow donor by vein if relapse after >4 weeks of imatinib.
Other Names:
  • buffy coat fusion
  • donor leukocyte infusion
  • apheresis
  • donor immune cell infusion
Procedure: Stem Cell Transplant
Infusion of donor bone marrow or blood stem cells by vein over approximately one hour on day 0.
Other Names:
  • stem cell infusion
  • stem cell transplant
  • stem cell transplantation
  • ALLOGENEIC STEM CELL TRANSPLANTATION
  • HSCT
  • hematopoietic stem cell transplant
  • Bone Marrow transplant
  • PBSC
  • Peripheral Blood Stem Cell

Detailed Description:

Patients will have blood and bone marrow tests performed as well as chest and sinus X-rays and tests of their heart and lung function. Approximately 5 tablespoons of blood will be drawn.

All patients in this study will receive imatinib mesylate by mouth for 9 days, unless the patient is known to be allergic or have symptomatic intolerance to the drug, or if the leukemia has failed to respond to imatinib. Fludarabine 40 mg/m2 by vein for 4 days (days -5 to -2), busulfan 130 mg/m2 by vein for 2 days (days -3 and -2), and ATG (Antithymocyte Globulin) 2.5 mg/kg by vein for 3 days (-3,-2 and -1).

Patients will then receive the donor bone marrow or blood stem cells by vein over approximately one hour on day 0.

After the infusion of the donor cells, you will receive immunosuppressive therapy with tacrolimus and methotrexate to decrease the risk of developing graft-vs-host disease (GvHD).

Patients will need frequent blood tests to monitor their counts and blood chemistries. This is generally done daily while in hospital and at least twice per week for the first 100 days post transplant. You may need frequent blood transfusions and may have to be admitted to the hospital to receive antibiotics if they develop fever. Bone marrow will be examined frequently beginning four weeks after treatment to evaluate response to treatment; Blood and bone marrow exams are to be performed at one, two three, six, 12 and 18 months post transplant and yearly thereafter for 5 years. To collect a bone marrow sample, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle.

Patients in whom treatment produces a remission, in which no sign of the leukemia can be detected, will receive no further therapy unless the leukemia recurs. Patients with evidence of leukemia after 3 months from the transplant will receive additional treatment with imatinib mesylate; those with detectable leukemia after an additional 3 months may receive an infusion of immune cells from the transplant donor.

If there is evidence of leukemia after the transplant, you will receive additional treatment with imatinib mesylate. If leukemia cells can still be detected, additional donor immune cells will be given to you by vein.

Patients are considered on the study for 5 years after the transplant.

A total of 90 patients will take part in this study. All will be enrolled at M. D. Anderson.

  Eligibility

Ages Eligible for Study:   up to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of Ph+ chronic myelogenous leukemia (CML) in first chronic phase without a complete hematologic response after 3 months of Imatinib mesylate therapy, or >=35% Ph+ cells despite > 6 months of Imatinib mesylate treatment, or after disease progression from a complete or partial response. Any patient with accelerated phase or blast crisis who achieves a subsequent chronic phase is eligible. Patients must have an HLA matched related or unrelated donor or one antigen mismatched related donor.
  2. Patients should be less than 70 years of age. Patients less than 30 years of age who achieve a hematologic remission with imatinib therapy are eligible regardless of cytogenetic response.
  3. Patients are stratified as Group 1: First chronic phase, Group 2 Accelerated phase or blast crisis that achieved a hematologic remission with imatinib mesylate-based treatment.

Exclusion Criteria:

  1. Zubrod Performance Scale (PS) >=2, uncontrolled infection, Creatinine > 2.0 mg/dl; Ejection fraction < 40%; Carbon Monoxide Diffusing Capacity (DLCO) < 45% of predicted; Serum bilirubin > 2 gm/dl; GPT (Glutamic-pyruvic transaminase) or GOT (glutamic-oxaloacetic transaminase)> 3 times normal values. Patients should not be human immunodeficiency virus (HIV) seropositive or pregnant.
  2. Patients should not have progressed to accelerated phase or blast crisis while receiving imatinib mesylate containing therapy.
  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: NCT00499889

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Richard E. Champlin, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00499889     History of Changes
Other Study ID Numbers: ID02-901
Study First Received: July 10, 2007
Results First Received: September 30, 2011
Last Updated: April 19, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Chronic Myelogenous Leukemia
Allogeneic Stem Cell Transplantation
Leukemia
Imatinib Mesylate
Gleevec
Busulfan
Busulfex
Myleran
Fludarabine
ATG
STI571
Antithymocyte Globulin
Thymoglobulin

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Antilymphocyte Serum
Busulfan
Methotrexate
Fludarabine phosphate
Tacrolimus
Fludarabine
Imatinib
Vidarabine
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic

ClinicalTrials.gov processed this record on August 01, 2014