Low-Dose or High-Dose Conditioning Followed by Peripheral Blood Stem Cell Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Myelogenous Leukemia

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT00322101
• Date of registration: 02/05/2006
• Prospective Registration: No
• Primary sponsor: Fred Hutchinson Cancer Research Center
• Public title: Low-Dose or High-Dose Conditioning Followed by Peripheral Blood Stem Cell Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Myelogenous Leukemia
• Scientific title: A Multi-center Phase III Study Comparing Myeloablative to Nonmyeloablative Transplant Conditioning in Patients With Myelodysplastic Syndrome or Acute Myelogenous Leukemia
• Date of first enrolment: January 2006
• Target sample size: 25
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00322101
• Study type: Interventional
• Phase: Phase 3

Countries of recruitment

Germany, United States

Contacts

• Name: Bart Scott
• Affiliation: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Key inclusion & exclusion criteria

Inclusion Criteria:

- Myelodysplastic syndrome (MDS) or transformed acute myelogenous leukemia (transformed
from MDS)

- De novo acute myelogenous leukemia (AML) beyond first remission

- Intermediate or high risk de novo AML in first complete response (at FHCRC unrelated
donor recipients only)

- Chemotherapy required prior to HCT for all patients:

- A) Interval between start of a cycle of cytoreductive chemotherapy and infusion of
donor stem cells must be at least 30 days; chemotherapy received for disease
maintenance will be allowed during this time period

- B) All patients must have < 5% myeloblasts based on marrow morphology performed within
21 days prior to start of conditioning regimen and at least 3-4 weeks after the start
of pre-transplant cytoreductive chemotherapy

- C) All patients must have no circulating peripheral blood myeloblasts present based on
morphologic analysis

- Age 65 years or under for patients with related donors; age 60 years or under for
patients with unrelated donors

- HCT-Specific Comorbidity Index Score (HCT-CI) < 3

- Related donor (age > 12 years, nonsyngeneic) or unrelated donor, HLA phenotypically or
genotypically identical at the allele level at A,B,C,DRQ1, and CBQ1

- DONOR: Related or unrelated donors who are genotypically or phenotypically matched by
high resolution HLA typing (HLA-A, B, C, DRB1, and DQB1); class 1 single allele
mismatch allowed

- DONOR: Patient and donor pairs homozygous at a mismatched allele in the graft
rejection vector are considered a two-allele mismatch, i.e., the patient is A*0101 and
the donor is A*0201, and this type of mismatch is not allowed

- DONOR: A positive anti-donor cytotoxic crossmatch or flow cytometric assay is an
absolute donor exclusion at FHCRC/SCCA

- DONOR: Age >= 12 years

- DONOR: Donors must consent to PBSC mobilization with G-CSF and leukaphereses; bone
marrow as a source of stem cells will not be allowed

- DONOR: Donor must have adequate veins for leukaphereses or agree to placement of
central venous catheter (femoral, subclavian)

Exclusion Criteria:

- HIV seropositivity

- Fungal infections with radiographic progression after appropriate therapy for greater
than one month

- Organ dysfunction

- Symptomatic coronary artery disease or ejection fraction < 35%

- DLCO < 65%, FEV1 < 65% or receiving supplementary continuous oxygen

- Liver function abnormalities: Patients with clinical or laboratory evidence of liver
disease will be evaluated for the cause of liver disease, its clinical severity in
terms of liver function, histology, and the degree of portal hypertension; patients
with fulminant liver failure, cirrhosis with evidence of portal hypertension or
bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding
esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic
dysfunction evidenced by prolongation of the prothrombin time, ascites related to
portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic
viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease
will be excluded

- Karnofsky Performance Score < 70

- Lansky-Play Performance Score < 70 for pediatric patients

- Life expectancy severely limited (< 2 years) by disease other than MDS/AML

- Fertile men and women unwilling to use contraceptive techniques during and for 12
months following treatment

- Patients with active non-hematological malignancies except:

- A) Patients with follicular or low grade lymphoma will be eligible as long as they
have not and do not require active treatment for control of their disease

- B) Patients with localized non-melanoma skin malignancies

- Patients with poorly controlled hypertension who are unable to have blood pressure
stabilized below 150/90 mm Hg on standard medication

- Females who are pregnant or breastfeeding

- Patients with systemic, uncontrolled infections

- Active CNS disease as identified by positive CSF cytospin

- DONOR: Identical twin

- DONOR: Age < 12 years

- DONOR: Pregnancy

- DONOR: HIV seropositivity

- DONOR: Inability to achieve adequate venous access

- DONOR: Known adverse reaction to G-CSF



Age minimum: N/A
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Previously Treated Myelodysplastic Syndromes

Recurrent Adult Acute Myeloid Leukemia

Acute Myeloid Leukemia/Transient Myeloproliferative Disorder

Adult Acute Myeloid Leukemia in Remission

Childhood Myelodysplastic Syndromes

Myelodysplastic Syndrome With Isolated Del(5q)

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities

Adult Acute Myeloid Leukemia With Del(5q)

Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)

Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)

Recurrent Childhood Acute Myeloid Leukemia

Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)

Childhood Acute Myeloid Leukemia in Remission

Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)

Secondary Myelodysplastic Syndromes

de Novo Myelodysplastic Syndromes

Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable

Secondary Acute Myeloid Leukemia

Intervention(s)

Genetic: polymorphism analysis

Other: flow cytometry

Drug: busulfan

Genetic: cytogenetic analysis

Procedure: allogeneic hematopoietic stem cell transplantation

Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation

Procedure: peripheral blood stem cell transplantation

Other: pharmacological study

Drug: cyclophosphamide

Drug: methotrexate

Radiation: total-body irradiation

Drug: tacrolimus

Other: laboratory biomarker analysis

Drug: cyclosporine

Drug: fludarabine phosphate

Drug: mycophenolate mofetil

Genetic: fluorescence in situ hybridization

Primary Outcome(s)

Overall Survival [Time Frame: At 2 years]

Secondary Outcome(s)

Incidence of Disease Progression/Relapse [Time Frame: After stem cell infusion to date of last follow up.]

Incidence and Severity of Acute and Chronic Graft-vs-host Disease [Time Frame: After transplantation]

Non-relapse Mortality [Time Frame: At 100 days]

Progression-free Survival [Time Frame: After stem cell infusion to date of last follow up.]

Donor Cell Engraftment [Time Frame: After stem cell infusion to day 28]

Secondary ID(s)

K23HL084054

P01HL036444

1992.00

NCI-2010-00737

P01CA018029

P01CA078902

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Cancer Institute (NCI)

National Heart, Lung, and Blood Institute (NHLBI)

Results

• Results available: Yes
• Date Posted: 28/10/2013
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00322101