LeukemiaPhase 1/2NCT00253513
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
A Phase 1/2 study testing fludarabine, treosulfan and allogeneic blood or bone marrow transplantation in people with Leukemia and Myelodysplastic Syndromes, run by OHSU Knight Cancer Institute at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 60 years
- Conditions the study is for
- Leukemia, Myelodysplastic Syndromes
- What is being tested?
- fludarabine, treosulfan and allogeneic blood or bone marrow transplantation
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 60 participants
- Where
- 3 sitesUnited States
- Study dates
- Jun 2005to Oct 2009
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 60 years
- All sexes
- No healthy volunteers
- Child, Adult
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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
OHSU Knight Cancer Institute
Portland, Oregon, 97239-3098
Seattle Cancer Care Alliance
Seattle, Washington, 98109-1023
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
About this study
Official title: A Study of a Reduced-Intensity Conditioning Regimen With Treosulfan and Fludarabine for Allogeneic Hematopoietic Cell Transplantation for Patients With Acute Leukemia
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.
Read the 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.
- Conditions
- Leukemia, Myelodysplastic Syndromes
- Being tested
- fludarabine, treosulfan, allogeneic blood or bone marrow transplantation
- 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
- Medical subject headings
- Leukemia, Myelodysplastic Syndromes, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
fludarabineDrug
30 mg/m2, IV for 5 days
treosulfanDrug
12 or 14 g/m2, IV for 5 days
allogeneic blood or bone marrow transplantationProcedure or surgery
bone marrow or peripheral blood stem cells
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 34 days and 2 years
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.
Measured: 42 days
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.
Measured: 200 days
Secondary outcomes (1)
Number of Subjects Who Are Without Disease at One Year as Indicator of Disease Free Survival.
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2005 (estimated)
- Study startJun 2005
- Primary completionOct 2009
- Study completionOct 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by OHSU Knight Cancer InstituteThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- OHSU Knight Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- medac GmbH, National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Eneida Nemecek, MD, Principal investigator, OHSU Knight Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00253513
- Sponsor's protocol ID
- CDR0000445306
- Other IDs
- FHCRC-1931.00, MEDAC-FHCRC-1931.00, OHSU-HEM-05107-LM, 1765
- Status last verified
- Feb 2011
- First submitted
- 11 Nov 2005
- Last updated
- 1 Jun 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of a Reduced-Intensity Conditioning Regimen With Treosulfan and Fludarabine for Allogeneic Hematopoietic Cell Transplantation for Patients With Acute Leukemia
- ClinicalTrials.gov ID
- NCT00253513
- Acronym / sponsor ID
- CDR0000445306
- Conditions
- 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
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- OHSU Knight Cancer InstituteUniversity, hospital or other
- Collaborators
- medac GmbH, National Cancer Institute (NCI)
- Study start
- Jun 2005
- Primary completion
- Oct 2009 (actual)
- Study completion
- Oct 2009 (actual)
- First posted
- 15 Nov 2005 (estimated)
- Results
- Posted 11 Feb 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- Up to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| fludarabine30 mg/m2, IV for 5 days | Drug | – |
| treosulfan12 or 14 g/m2, IV for 5 days | Drug | – |
| allogeneic blood or bone marrow transplantationbone marrow or peripheral blood stem cells | Procedure or surgery | – |
Primary outcome
Number of Patients Experiencing Regimen-related Toxicity Events in Study Population
Time frame: 34 days and 2 years
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
Time frame: 42 days
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)
Time frame: 200 days
NRM (Non relapse mortality) - death not attributed to the primary cancer.
1 secondary outcome
Number of Subjects Who Are Without Disease at One Year as Indicator of Disease Free Survival.
Time frame: One year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eneida Nemecek, MD principal investigator
OHSU Knight Cancer Institute
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing fludarabine, treosulfan and allogeneic blood or bone marrow transplantation in people with Leukemia and Myelodysplastic Syndromes, run by OHSU Knight Cancer Institute at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Feb 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients Experiencing Regimen-related Toxicity Events in Study Population (time frame: 34 days and 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2012.