NCT00499889

Brief Summary

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
42

participants targeted

Target at P50-P75 for phase_2 leukemia

Timeline
Completed

Started Feb 2003

Typical duration for phase_2 leukemia

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2003

Completed
4.4 years until next milestone

First Submitted

Initial submission to the registry

July 10, 2007

Completed
2 days until next milestone

First Posted

Study publicly available on registry

July 12, 2007

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2009

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2009

Completed
2 years until next milestone

Results Posted

Study results publicly available

November 7, 2011

Completed
Last Updated

April 23, 2012

Status Verified

April 1, 2012

Enrollment Period

6.8 years

First QC Date

July 10, 2007

Results QC Date

September 30, 2011

Last Update Submit

April 19, 2012

Conditions

Keywords

Chronic Myelogenous LeukemiaAllogeneic Stem Cell TransplantationLeukemiaImatinib MesylateGleevecBusulfanBusulfexMyleranFludarabineATGSTI571Antithymocyte GlobulinThymoglobulin

Outcome Measures

Primary Outcomes (1)

  • Number of Participants in Complete Molecular Remission at 1 Year

    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).

    Baseline to 1 year

Secondary Outcomes (2)

  • Participants' With mCR Response to Post Transplant Imatinib Mesylate Therapy

    1 Year

  • Participants' With mCR Response to Post Transplant DLI

    1 year

Study Arms (1)

Imatinib, Busulfan, Fludara + Antithymocyte Globulin

EXPERIMENTAL

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 MesylateDrug: Fludarabine (Fludara)Drug: BusulfanDrug: Antithymocyte Globulin (ATG)Drug: TacrolimusDrug: MethotrexateProcedure: Donor lymphocyte infusion (DLI)Procedure: Stem Cell Transplant

Interventions

400 mg by mouth twice daily for 9 Days

Also known as: Gleevec, STI571
Imatinib, Busulfan, Fludara + Antithymocyte Globulin

40 mg/m\^2 by vein daily for 4 Days

Also known as: Fludarabine Phosphate, Fludara, Fludarabine
Imatinib, Busulfan, Fludara + Antithymocyte Globulin

130 mg/m\^2 by vein daily for 2 Days

Also known as: Busulfex, Myleran
Imatinib, Busulfan, Fludara + Antithymocyte Globulin

2.5 mg/kg by vein daily for 3 Days

Also known as: ATG, Thymoglobulin
Imatinib, Busulfan, Fludara + Antithymocyte Globulin

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.

Also known as: Prograf
Imatinib, Busulfan, Fludara + Antithymocyte Globulin

5 mg/m2 on days 1, 3, 6 and 11.

Imatinib, Busulfan, Fludara + Antithymocyte Globulin

Infusion of lymphocytes from the original bone marrow donor by vein if relapse after \>4 weeks of imatinib.

Also known as: buffy coat fusion, donor leukocyte infusion, apheresis, donor immune cell infusion
Imatinib, Busulfan, Fludara + Antithymocyte Globulin

Infusion of donor bone marrow or blood stem cells by vein over approximately one hour on day 0.

Also known as: stem cell infusion, stem cell transplantation, ALLOGENEIC STEM CELL TRANSPLANTATION, HSCT, hematopoietic stem cell transplant, Bone Marrow transplant, PBSC, Peripheral Blood Stem Cell
Imatinib, Busulfan, Fludara + Antithymocyte Globulin

Eligibility Criteria

AgeUp to 70 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • 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.
  • 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.

You may not qualify if:

  • 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.
  • Patients should not have progressed to accelerated phase or blast crisis while receiving imatinib mesylate containing therapy.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

MeSH Terms

Conditions

LeukemiaLeukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Imatinib Mesylatefludarabinefludarabine phosphateBusulfanAntilymphocyte SerumthymoglobulinTacrolimusMethotrexateBlood Component RemovalStem Cell TransplantationBone Marrow TransplantationPeripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLeukemia, MyeloidMyeloproliferative DisordersBone Marrow DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

BenzamidesAmidesOrganic ChemicalsBenzoatesAcids, CarbocyclicCarboxylic AcidsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsPiperazinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPyrimidinesButylene GlycolsGlycolsAlcoholsMesylatesAlkanesulfonatesAlkanesulfonic AcidsAlkanesHydrocarbons, AcyclicSulfonic AcidsSulfur AcidsSulfur CompoundsImmune SeraAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsBiological ProductsComplex MixturesMacrolidesLactonesAminopterinPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingTherapeuticsCell TransplantationCell- and Tissue-Based TherapyBiological TherapyTransplantationSurgical Procedures, OperativeTissue TransplantationHematopoietic Stem Cell Transplantation

Limitations and Caveats

Study completed early due to support issues.

Results Point of Contact

Title
Richard E. Champlin, MD/Professor
Organization
UT MD Anderson Cancer Center

Study Officials

  • Richard E. Champlin, MD

    M.D. Anderson Cancer Center

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 10, 2007

First Posted

July 12, 2007

Study Start

February 1, 2003

Primary Completion

November 1, 2009

Study Completion

November 1, 2009

Last Updated

April 23, 2012

Results First Posted

November 7, 2011

Record last verified: 2012-04

Locations