Trial Outcomes & Findings for 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 (NCT NCT00253513)

Last Updated: 2012-06-01

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

60 participants

Primary outcome timeframe

34 days and 2 years

Results posted on

2012-06-01

Participant Flow

Patients recruited at OHSU Knight Cancer Institute clinics in Portland, Oregon and Fred Hutchinson Cancer Research Center or University of Washington Medical Center clinics, Seattle, Washington.

Participant milestones

Participant milestones
Measure	Treosulfan and Fludarabine Conditioning Conditioning with Treosulfan (12 or 14 g/m2, IV for 5 days) and Fludarabine (30 mg/m2, IV for 5 days) followed by Allogeneic Hematopoietic Cell Transplantation for High-Risk Hematologic Malignancies
Overall Study STARTED	60
Overall Study COMPLETED	60
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treosulfan and Fludarabine Conditioning n=60 Participants Conditioning with Treosulfan (12 or 14 g/m2, IV for 5 days) and Fludarabine (30 mg/m2, IV for 5 days) followed by Allogeneic Hematopoietic Cell Transplantation for High-Risk Hematologic Malignancies
Age, Customized < 21 years	10 Participants n=5 Participants
Age, Customized Between 21 - 50 years	31 Participants n=5 Participants
Age, Customized Between 50 - 60 years	19 Participants n=5 Participants
Sex: Female, Male Female	36 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants
Region of Enrollment United States	60 participants n=5 Participants
Disease status at transplantation Acute Lymphoblastic Leukemia(ALL)2nd/3rd remission	3 Participants n=5 Participants
Disease status at transplantation Acute Myelogenous Leukemia(AML)1st remission	26 Participants n=5 Participants
Disease status at transplantation AML, 2nd or greater remission.	10 Participants n=5 Participants
Disease status at transplantation AML, relapsed or primary refractory	8 Participants n=5 Participants
Disease status at transplantation Myelodysplastic Syndrome(MDS): Refract. Anemia(RA)	6 Participants n=5 Participants
Disease status at transplantation MDS: RA with excess blasts in transformation	7 Participants n=5 Participants
Disease risk group Low - AML/ALL in 1st rem., MDS with IPSS=0	26 Participants n=5 Participants
Disease risk group Standard (ALL or AML in 2nd or greater rem.)	22 Participants n=5 Participants
Disease risk group High -relapsed/refract. ALL/AML/MDS w/ IPSS>=2.5	12 Participants n=5 Participants
Cytogenetic risk group Good	16 Participants n=5 Participants
Cytogenetic risk group Intermediate	8 Participants n=5 Participants
Cytogenetic risk group Poor	36 Participants n=5 Participants
Hematopoietic Cell Transplantation Comorbidity Index (HCT CI) 0	13 Participants n=5 Participants
Hematopoietic Cell Transplantation Comorbidity Index (HCT CI) 1-2	19 Participants n=5 Participants
Hematopoietic Cell Transplantation Comorbidity Index (HCT CI) >=3	28 Participants n=5 Participants
Donor type HLA (human leukocyte antigen) -identical sibling	30 participants n=5 Participants
Donor type HLA-matched unrelated donor	30 participants n=5 Participants
Stem cell source Bone marrow	7 participants n=5 Participants
Stem cell source Filgrastim-mobilized PBPC	53 participants n=5 Participants

PRIMARY outcome

Timeframe: 34 days and 2 years

Outcome measures

Outcome measures
Measure	Treosulfan and Fludarabine Conditioning n=60 Participants Conditioning with Treosulfan (12 or 14 g/m2, IV for 5 days) and Fludarabine (30 mg/m2, IV for 5 days) followed by Allogeneic Hematopoietic Cell Transplantation for High-Risk Hematologic Malignancies
Number of Patients Experiencing Regimen-related Toxicity Events in Study Population Severe Regimen Related Toxicity (RRT)	2 participants
Number of Patients Experiencing Regimen-related Toxicity Events in Study Population Nonrelapse mortality at 2 years	5 participants

PRIMARY outcome

Timeframe: 42 days

Population: For graft failure 2 of the 60 patients were not evaluable because they exeperienced another event (relapsed) before they could be evaluable for 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.

Outcome measures

Outcome measures
Measure	Treosulfan and Fludarabine Conditioning n=58 Participants Conditioning with Treosulfan (12 or 14 g/m2, IV for 5 days) and Fludarabine (30 mg/m2, IV for 5 days) followed by Allogeneic Hematopoietic Cell Transplantation for High-Risk Hematologic Malignancies
Number of Patients Experiencing Graft Failure acute graft vs. host disease (aGVHD)	36 participants
Number of Patients Experiencing Graft Failure chronic graft vs. host disease (cGVHD)	31 participants

PRIMARY outcome

Timeframe: 200 days

NRM (Non relapse mortality) - death not attributed to the primary cancer.

Outcome measures

Outcome measures
Measure	Treosulfan and Fludarabine Conditioning n=60 Participants Conditioning with Treosulfan (12 or 14 g/m2, IV for 5 days) and Fludarabine (30 mg/m2, IV for 5 days) followed by Allogeneic Hematopoietic Cell Transplantation for High-Risk Hematologic Malignancies
Incidence (Percent of Participants) With Nonrelapse Mortality (NRM) by Day 200 (Secondary Phase Only)	5 percent of participants Interval 0.0 to 10.5

SECONDARY outcome

Timeframe: One year

Outcome measures

Outcome measures
Measure	Treosulfan and Fludarabine Conditioning n=60 Participants Conditioning with Treosulfan (12 or 14 g/m2, IV for 5 days) and Fludarabine (30 mg/m2, IV for 5 days) followed by Allogeneic Hematopoietic Cell Transplantation for High-Risk Hematologic Malignancies
Number of Subjects Who Are Without Disease at One Year as Indicator of Disease Free Survival.	58 participants

Adverse Events

Treosulfan and Fludarabine Conditioning

Serious events: 5 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treosulfan and Fludarabine Conditioning n=60 participants at risk Conditioning with Treosulfan (12 or 14 g/m2, IV for 5 days) and Fludarabine (30 mg/m2, IV for 5 days) followed by Allogeneic Hematopoietic Cell Transplantation for High-Risk Hematologic Malignancies
Respiratory, thoracic and mediastinal disorders Grade 4 mucositis	1.7% 1/60 • Number of events 1
Immune system disorders Death - cGVHD	3.3% 2/60 • Number of events 2
Blood and lymphatic system disorders Death - intracranial hemmorrage	1.7% 1/60 • Number of events 1
Infections and infestations Death - fungal infection	3.3% 2/60 • Number of events 2

Other adverse events

Adverse event data not reported

Additional Information

Eneida Nemecek, MD

OHSU Knight Cancer Institute

Phone: (503) 494-0829

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place