Chronic Myeloproliferative DisordersPhase 2NCT00346359

Fludarabine and Busulfan Followed by Donor Peripheral Stem Cell Transplant and Antithymocyte Globulin, Tacrolimus, and Methotrexate in Treating Patients With Myeloid Cancer

A Phase 2 study testing anti-thymocyte globulin, busulfan and fludarabine phosphate in people with Chronic Myeloproliferative Disorders and Graft Versus Host Disease, run by Fred Hutchinson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages Up to 65 years
Conditions the study is for: Chronic Myeloproliferative Disorders, Graft Versus Host Disease, Leukemia
What is being tested?: anti-thymocyte globulin, busulfan and fludarabine phosphate
Type of treatment: Surgery or procedure
How many people: 40 participants
Where: 1 siteUnited States
Study dates: Mar 2006to Nov 2007
Phase: Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Up to 65 years
All sexes
No healthy volunteers
Child, Adult, Older adult

DISEASE CHARACTERISTICS:

Diagnosis of 1 of the following myeloid malignancies:
Chronic myelogenous leukemia meeting 1 of the following criteria:
Chronic phase
Accelerated phase
Treated blast phase
Acute myeloid leukemia meeting 1 of the following criteria:
In remission
In early relapse, defined as < 10% marrow blasts
Myelodysplastic syndromes, including all risk groups
Other myeloproliferative disorders
HLA-A, -B, -C, -DRB1, and -DQB1 matched related or unrelated donor available

PATIENT CHARACTERISTICS:

No other disease that would severely limit life expectancy
AST ≤ 2 times normal
Creatinine ≤ 2 times normal OR creatinine clearance ≥ 60 mL/min
No cardiac insufficiency requiring treatment
No symptomatic coronary artery disease
PO_2 ≥ 70 mm Hg AND DLCO ≥ 70% of predicted OR PO _2 ≥ 80 mm Hg AND DLCO ≥ 60% of predicted
HIV negative
Not pregnant or nursing
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

No post-transplantation growth factor during methotrexate administration

Trial locations and contacts

1 site in 1 country.

United States1 site

Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109-1024

Other trials in United States

About this study

Official title: Conditioning For Hematopoietic Cell Transplantation With Fludarabine Plus Targeted IV Busulfan and GVHD Prophylaxis With Thymoglobulin, Tacrolimus and Methotrexate in Patients With Myeloid Malignancies

RATIONALE: Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor peripheral stem cell transplant helps stop the growth of abnormal and cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining abnormal or cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving antithymocyte globulin, tacrolimus, and methotrexate before or after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving fludarabine together with busulfan followed by donor peripheral stem cell transplant and antithymocyte globulin, tacrolimus, and methotrexate works in treating patients with myeloid cancer.

Read the detailed description

OBJECTIVES:

Primary

Determine the incidence and severity of acute graft-versus-host disease (GVHD) in patients with myeloid malignancies treated with conditioning regimen comprising fludarabine phosphate and busulfan followed by allogeneic peripheral blood stem cell transplantation and GVHD prophylaxis comprising antithymocyte globulin, tacrolimus, and methotrexate.
Determine the incidence of donor engraftment in patients treated with this regimen.

Secondary

Determine the pharmacokinetics of IV busulfan, including interdose variability and evaluation of a limited sampling strategy, in these patients.
Determine the pharmacokinetics of antithymocyte globulin in these patients.
Determine the pharmacokinetics of fludarabine phosphate and its effect on lymphocytes in these patients.
Determine the incidence of specific toxic effects ≥ grade 3 in patients treated with this regimen.
Determine the incidence and severity of chronic GVHD in these patients.
Determine the incidence of nonrelapsing mortality at 100 days and at 1 year after transplantation in these patients.
Determine the incidence of relapse in these patients.
Determine relapse-free survival of these patients.
Determine the incidence of Epstein-Barr virus activation in these patients.

OUTLINE:

Conditioning regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2 and busulfan IV over 3 hours on days -5 to -2. Prior to the conditioning regimen, patients whose cerebrospinal fluid is positive for malignant cells receive intrathecal methotrexate or cranial irradiation for CNS prophylaxis.
Allogeneic peripheral blood stem cell (PBSC) transplantation: Patients receive filgrastim (G-CSF)-mobilized allogeneic PBSCs IV on day 0.
Graft-versus-host disease prophylaxis: Patients receive antithymocyte globulin IV over at least 10 hours on days -3 to -1. They also receive tacrolimus orally twice daily or IV continuously beginning on day -1 and continuing until up to day 55, followed by a taper until day 180 in the absence of graft-versus-host disease. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

After completion of study treatment, patients are followed annually.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Conditions: Chronic Myeloproliferative Disorders, Graft Versus Host Disease, Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases
Being tested: anti-thymocyte globulin, busulfan, fludarabine phosphate, methotrexate, tacrolimus
Keywords: graft versus host disease, chronic phase chronic myelogenous leukemia, childhood chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, accelerated phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, adult acute myeloid leukemia in remission, recurrent adult acute myeloid leukemia, childhood acute myeloid leukemia in remission, recurrent childhood acute myeloid leukemia, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, atypical chronic myeloid leukemia, chronic myelomonocytic leukemia, juvenile myelomonocytic leukemia, myelodysplastic/myeloproliferative disease, unclassifiable, secondary acute myeloid leukemia, chronic eosinophilic leukemia, chronic idiopathic myelofibrosis
Medical subject headings: Myeloproliferative Disorders, Graft vs Host Disease, Leukemia, Myelodysplastic Syndromes, Myelodysplastic-Myeloproliferative Diseases, Leukemia, Myeloid, Chronic-Phase, Blast Crisis, Leukemia, Myeloid, Accelerated Phase

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

anti-thymocyte globulinBiological
busulfanDrug
fludarabine phosphateDrug
methotrexateDrug
tacrolimusDrug
allogeneic hematopoietic stem cell transplantationProcedure or surgery
peripheral blood stem cell transplantationProcedure or surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

Incidence and severity of acute graft-versus-host disease (GVHD)
Incidence of donor engraftment

Secondary outcomes (9)

Pharmacokinetics of IV busulfan including interdose variability and evaluation of a limited sampling strategy
Pharmacokinetics of antithymocyte globulin
Pharmacokinetics of fludarabine phosphate and its effect on lymphocytes
Incidence of specific toxic effects ≥ grade 3
Incidence and severity of chronic GVHD
Incidence of nonrelapsing mortality at 100 days and at 1 year after transplantation
Incidence of relapse
Relapse-free survival
Incidence of Epstein-Barr virus activation and post-transplantation lymphoproliferative disease

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2006Nov 2007

First posted29 Jun 2006 (estimated)
Study startMar 2006
Study completionNov 2007

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Chronic Myeloproliferative DisordersStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Masking: None (open label)
Enrolment: 40 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00346359
Sponsor's protocol ID: 2041.00
Other IDs: FHCRC-2041.00, GEMZYME-FHCRC-2041.00, CDR0000488969
Status last verified: May 2010
First submitted: 28 Jun 2006
Last updated: 14 May 2010
Results posted: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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