Back to resultsTreosulfan and Fludarabine in Treating Younger Patients Who Are Undergoing a Donor Stem Cell Transplant for Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome
Primary Purpose
Leukemia, Myelodysplastic Syndromes
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
fludarabine
treosulfan
allogeneic blood or bone marrow transplantation
Sponsored by
About this trial
This is an interventional treatment trial for Leukemia focused on measuring adult acute lymphoblastic leukemia in remission, adult acute myeloid leukemia in remission, childhood acute lymphoblastic leukemia in remission, recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia, recurrent childhood acute lymphoblastic leukemia, recurrent childhood acute myeloid leukemia, secondary acute myeloid leukemia, myelodysplastic syndromes, childhood myelodysplastic syndromes
Eligibility Criteria
DISEASE CHARACTERISTICS: Diagnosis of acute myeloid leukemia, lymphoblastic leukemia, or myelodysplastic syndrome Any phase allowed, including any of the following: Disease in remission Relapsed or primary refractory disease No CNS leukemic involvement not clearing with prior intrathecal chemotherapy and/or cranial radiotherapy Planning to undergo unmanipulated allogeneic bone marrow or peripheral blood stem cell transplantation Filgrastim (G-CSF) mobilization of bone marrow or stem cells allowed Donor available, meeting 1 of the following criteria: HLA-identical related donor HLA-A, -B, -C, -DRB1, and -DQB1 matched unrelated donor by high-resolution DNA typing A single allele mismatch allowed PATIENT CHARACTERISTICS: Performance status Karnofsky 70-100% OR Lansky 70-100% Life expectancy Not specified Hematopoietic Not specified Hepatic Bilirubin ≤ 2 times upper limit of normal (ULN) AST ≤ 2 times ULN No evidence of synthetic dysfunction No severe cirrhosis No active infectious hepatitis Renal Creatinine clearance ≥ 50% Creatinine ≤ 2 times ULN Dialysis independent Cardiovascular No cardiac insufficiency requiring treatment No symptomatic coronary artery disease Ejection fraction ≥ 35% (for patients with history of cardiac disease or anthracycline exposure) Pulmonary PO_2 ≥ 70 mm Hg AND DLCO ≥ 70% of predicted OR PO_2 ≥ 80 mm Hg AND DLCO ≥ 60% of predicted Not requiring supplementary continuous oxygen Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other disease that would severely limit life expectancy No HIV positivity No active infection requiring deferral of conditioning No known hypersensitivity to the study drugs PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics No prior allogeneic bone marrow or stem cell transplantation No concurrent umbilical cord blood or autologous transplantation Chemotherapy See Disease Characteristics Radiotherapy See Disease Characteristics Other More than 4 weeks since prior experimental drugs Concurrent enrollment on another protocol for graft-versus-host disease prophylaxis allowed
Sites / Locations
- OHSU Knight Cancer Institute
- Seattle Cancer Care Alliance
- Fred Hutchinson Cancer Research Center
Outcomes
Primary Outcome Measures
Number of Patients Experiencing Regimen-related Toxicity Events in Study Population
Proportion of patients experiencing regimen-related toxicity to major organ systems from day minus 6 to day 28. Major organ systems: cardiac, bladder/renal, pulmonary, hepatic, neurologic and gastrointestinal
Number of Patients Experiencing Graft Failure
Graft versus Host Disease (GVHD) is a frequent complication of allogeneic bone marrow transplant in which the engrafted donor cells attacks the patient's organs and tissue. Acute GVHD (aGVHD) usually occurs during the first three months following an allogeneic BMT. Chronic GVHD (cGVHD) usually develops after the third month post-transplant. Patients may experience one, both or neither.
Incidence (Percent of Participants) With Nonrelapse Mortality (NRM) by Day 200 (Secondary Phase Only)
NRM (Non relapse mortality) - death not attributed to the primary cancer.
Secondary Outcome Measures
Number of Subjects Who Are Without Disease at One Year as Indicator of Disease Free Survival.
Full Information
NCT ID
NCT00253513
First Posted
November 11, 2005
Last Updated
May 24, 2012
Sponsor
OHSU Knight Cancer Institute
Collaborators
medac GmbH, National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00253513
Brief Title
Treosulfan and Fludarabine in Treating Younger Patients Who Are Undergoing a Donor Stem Cell Transplant for Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome
Official Title
A Study of a Reduced-Intensity Conditioning Regimen With Treosulfan and Fludarabine for Allogeneic Hematopoietic Cell Transplantation for Patients With Acute Leukemia
Study Type
Interventional
2. Study Status
Record Verification Date
February 2011
Overall Recruitment Status
Completed
Study Start Date
June 2005 (undefined)
Primary Completion Date
October 2009 (Actual)
Study Completion Date
October 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
OHSU Knight Cancer Institute
Collaborators
medac GmbH, National Cancer Institute (NCI)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
RATIONALE: Drugs used in chemotherapy, such as treosulfan and fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving treosulfan and fludarabine together with a donor bone marrow transplant or a peripheral stem cell transplant may be an effective treatment for acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome.
PURPOSE: This phase II trial is studying giving treosulfan together with fludarabine to see how well it works in treating patients who are undergoing a donor stem cell transplant for acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome.
Detailed Description
OBJECTIVES:
Primary Phase
Determine the best dose of treosulfan when administered with fludarabine as a reduced-intensity conditioning regimen followed by allogeneic hematopoietic stem cell transplantation, in terms of incidence of severe to fatal toxicity to major organ systems and incidence of graft failure, in patients with acute myeloid leukemia, lymphoblastic leukemia, or myelodysplastic syndrome.
Secondary Phase
Determine the safety of this regimen, in terms of incidence of grade II-IV acute and chronic graft-versus-host disease, in these patients.
Determine, preliminarily, the efficacy of this regimen, in terms of incidence of relapse, overall and disease-free survival, donor chimerism on days 28 and 100, and incidence of 200-day and 1-year nonrelapse mortality, in these patients.
Determine the pharmacokinetic and pharmacodynamic profile of treosulfan in patients treated with this regimen.
OUTLINE: This is a multicenter, dose-finding study of treosulfan.
Reduced-intensity conditioning: Patients receive treosulfan IV over 2 hours on days -6 to -4 and fludarabine IV over 30 minutes on days -6 to -2.
Cohorts of 5-10 patients receive escalating/de-escalating doses of treosulfan until the best dose is determined among the 3 pre-selected doses. The best dose is defined as the dose preceding that at which 4 of 10 patients experience dose-limiting toxicity.
Allogeneic hematopoietic cell transplantation (AHCT): Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0.
All male patients with acute lymphoblastic leukemia OR male patients with acute myeloid leukemia who have prior or current testicular involvement receive external-beam radiotherapy to the testicles before AHCT.
After completion of study treatment, patents are followed periodically.
PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Myelodysplastic Syndromes
Keywords
adult acute lymphoblastic leukemia in remission, adult acute myeloid leukemia in remission, childhood acute lymphoblastic leukemia in remission, recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia, recurrent childhood acute lymphoblastic leukemia, recurrent childhood acute myeloid leukemia, secondary acute myeloid leukemia, myelodysplastic syndromes, childhood myelodysplastic syndromes
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
fludarabine
Intervention Description
30 mg/m2, IV for 5 days
Intervention Type
Drug
Intervention Name(s)
treosulfan
Intervention Description
12 or 14 g/m2, IV for 5 days
Intervention Type
Procedure
Intervention Name(s)
allogeneic blood or bone marrow transplantation
Intervention Description
bone marrow or peripheral blood stem cells
Primary Outcome Measure Information:
Title
Number of Patients Experiencing Regimen-related Toxicity Events in Study Population
Description
Proportion of patients experiencing regimen-related toxicity to major organ systems from day minus 6 to day 28. Major organ systems: cardiac, bladder/renal, pulmonary, hepatic, neurologic and gastrointestinal
Time Frame
34 days and 2 years
Title
Number of Patients Experiencing Graft Failure
Description
Graft versus Host Disease (GVHD) is a frequent complication of allogeneic bone marrow transplant in which the engrafted donor cells attacks the patient's organs and tissue. Acute GVHD (aGVHD) usually occurs during the first three months following an allogeneic BMT. Chronic GVHD (cGVHD) usually develops after the third month post-transplant. Patients may experience one, both or neither.
Time Frame
42 days
Title
Incidence (Percent of Participants) With Nonrelapse Mortality (NRM) by Day 200 (Secondary Phase Only)
Description
NRM (Non relapse mortality) - death not attributed to the primary cancer.
Time Frame
200 days
Secondary Outcome Measure Information:
Title
Number of Subjects Who Are Without Disease at One Year as Indicator of Disease Free Survival.
Time Frame
One year
10. Eligibility
Sex
All
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS:
Diagnosis of acute myeloid leukemia, lymphoblastic leukemia, or myelodysplastic syndrome
Any phase allowed, including any of the following:
Disease in remission
Relapsed or primary refractory disease
No CNS leukemic involvement not clearing with prior intrathecal chemotherapy and/or cranial radiotherapy
Planning to undergo unmanipulated allogeneic bone marrow or peripheral blood stem cell transplantation
Filgrastim (G-CSF) mobilization of bone marrow or stem cells allowed
Donor available, meeting 1 of the following criteria:
HLA-identical related donor
HLA-A, -B, -C, -DRB1, and -DQB1 matched unrelated donor by high-resolution DNA typing
A single allele mismatch allowed
PATIENT CHARACTERISTICS:
Performance status
Karnofsky 70-100% OR
Lansky 70-100%
Life expectancy
Not specified
Hematopoietic
Not specified
Hepatic
Bilirubin ≤ 2 times upper limit of normal (ULN)
AST ≤ 2 times ULN
No evidence of synthetic dysfunction
No severe cirrhosis
No active infectious hepatitis
Renal
Creatinine clearance ≥ 50%
Creatinine ≤ 2 times ULN
Dialysis independent
Cardiovascular
No cardiac insufficiency requiring treatment
No symptomatic coronary artery disease
Ejection fraction ≥ 35% (for patients with history of cardiac disease or anthracycline exposure)
Pulmonary
PO_2 ≥ 70 mm Hg AND DLCO ≥ 70% of predicted OR
PO_2 ≥ 80 mm Hg AND DLCO ≥ 60% of predicted
Not requiring supplementary continuous oxygen
Other
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No other disease that would severely limit life expectancy
No HIV positivity
No active infection requiring deferral of conditioning
No known hypersensitivity to the study drugs
PRIOR CONCURRENT THERAPY:
Biologic therapy
See Disease Characteristics
No prior allogeneic bone marrow or stem cell transplantation
No concurrent umbilical cord blood or autologous transplantation
Chemotherapy
See Disease Characteristics
Radiotherapy
See Disease Characteristics
Other
More than 4 weeks since prior experimental drugs
Concurrent enrollment on another protocol for graft-versus-host disease prophylaxis allowed
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eneida Nemecek, MD
Organizational Affiliation
OHSU Knight Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
OHSU Knight Cancer Institute
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239-3098
Country
United States
Facility Name
Seattle Cancer Care Alliance
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109-1023
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Treosulfan and Fludarabine in Treating Younger Patients Who Are Undergoing a Donor Stem Cell Transplant for Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome
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