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A Multi-center Phase III Study Comparing Myeloablative to Nonmyeloablative Transplant Conditioning in Patients With Myelodysplastic Syndrome or Acute Myelogenous Leukemia


Phase 3
N/A
65 Years
Open (Enrolling)
Both
Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, Acute Myeloid Leukemia/Transient Myeloproliferative Disorder, Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Childhood Acute Myeloid Leukemia in Remission, Childhood Myelodysplastic Syndromes, de Novo Myelodysplastic Syndromes, Myelodysplastic Syndrome With Isolated Del(5q), Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable, Previously Treated Myelodysplastic Syndromes, Recurrent Adult Acute Myeloid Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Secondary Acute Myeloid Leukemia, Secondary Myelodysplastic Syndromes

Thank you

Trial Information

A Multi-center Phase III Study Comparing Myeloablative to Nonmyeloablative Transplant Conditioning in Patients With Myelodysplastic Syndrome or Acute Myelogenous Leukemia


OBJECTIVES:

I. Determine whether the conditioning intensity affects outcomes after HCT in patients with
MDS or AML who have < 5% marrow myeloblasts at the time of HCT.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

Arm I (Nonmyeloablative regimen):

CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo
low-dose total-body irradiation on day 0.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) infusion on
day 0.

GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine every 12 hours on days -3
to 57 with taper on days 57-177 or cyclosporine every 12 hours on days -3 to 100 with taper
on days 101-177. Patients also receive oral mycophenolate mofetil every 12 hours on days
0-27 or every 8 hours on days 0-40 with taper on days 41-96.

Arm II (Myeloablative regimen):

CONDITIONING: Patients are assigned to 1 of 2 treatment groups.

Group A: Patients receive fludarabine IV once daily and oral busulfan four times daily or
busulfan IV over 3 hours on days -5 to -2.

Group B: Patients receive cyclophosphamide IV over 1-2 hours on days -3 and -2 and oral
busulfan four times daily or busulfan IV over 3 hours on days -7 to -4.

TRANSPLANTATION: Patients undergo PBSC infusion on day 0.

GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV continuously or orally
every 12 hours on days -1 to 56 and taper on days 57-200. Patients also receive methotrexate
IV on days 1, 3, 6, and 11.

Treatment in both arms continues in the absence of disease progression or unacceptable
toxicity.

After completion of study treatment, patients are followed up periodically.


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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall survival

Outcome Time Frame:

At 2 years

Safety Issue:

No

Principal Investigator

Bart Scott

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Federal Government

Study ID:

1992.00

NCT ID:

NCT00322101

Start Date:

January 2006

Completion Date:

Related Keywords:

  • Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome
  • Acute Myeloid Leukemia/Transient Myeloproliferative Disorder
  • Adult Acute Myeloid Leukemia in Remission
  • Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
  • Adult Acute Myeloid Leukemia With Del(5q)
  • Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
  • Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
  • Childhood Acute Myeloid Leukemia in Remission
  • Childhood Myelodysplastic Syndromes
  • de Novo Myelodysplastic Syndromes
  • Myelodysplastic Syndrome With Isolated Del(5q)
  • Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
  • Previously Treated Myelodysplastic Syndromes
  • Recurrent Adult Acute Myeloid Leukemia
  • Recurrent Childhood Acute Myeloid Leukemia
  • Secondary Acute Myeloid Leukemia
  • Secondary Myelodysplastic Syndromes
  • Congenital Abnormalities
  • Neoplasms
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Myelodysplastic-Myeloproliferative Diseases

Name

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109
University of UtahSalt Lake City, Utah  
Emory UniversityAtlanta, Georgia  30322
Veterans Administration Center-SeattleSeattle, Washington  98108
HealthOne Presbyterian St. Lukes Medical CenterDenver, Colorado  
Weill Cornell UniversityNew York, New York  10021
Medical College WisconsinMilwaukee, Wisconsin