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Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation From HLA Matched Unrelated Donors for Treatment of Patients With High Risk Acute Lymphocytic Leukemia in Complete Remission - A Multicenter Trial


Phase 2
N/A
75 Years
Not Enrolling
Both
Adult Acute Lymphoblastic Leukemia in Remission, Childhood Acute Lymphoblastic Leukemia in Remission, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Lymphoblastic Leukemia

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Trial Information

Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation From HLA Matched Unrelated Donors for Treatment of Patients With High Risk Acute Lymphocytic Leukemia in Complete Remission - A Multicenter Trial


PRIMARY OBJECTIVES:

I. To determine if a one-year disease-free survival (DFS) of > 25% can be achieved among
adult patients with high risk acute lymphocytic leukemia (ALL) in complete remission (CR)
who undergo nonmyeloablative allografting.

II. To determine if a one-year DFS of >= 40% can be achieved among pediatric patients with
high risk ALL in CR who undergo nonmyeloablative allografting.

SECONDARY OBJECTIVES:

I. To determine if a day +200 transplant-related mortality (TRM) of < 25% can be achieved
among patients with high risk ALL in CR who undergo nonmyeloablative allografting.

II. To evaluate the efficacy and toxicity of donor lymphocyte infusion (DLI) in the
treatment of minimal residue disease (MRD) after nonmyeloablative allografting for patients
with high risk ALL in CR.

OUTLINE:

NONMYELOALATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously
(IV) on days -4 to -2 and undergo total body irradiation (TBI) on day 0.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation
(PBSCT) on day 0. Patients with minimal residual disease may receive donor lymphocyte
infusion IV.

IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) every 12 hours on days -3 to
100 with taper to day 177 and mycophenolate mofetil PO very 8 hours on days 0 to 40 with
taper to day 96.

After completion of study treatment, patients are followed up at days 28, 56, 84, 120, 180,
and 360; at 18 months; and annually for up to 5 years.


Inclusion Criteria:



- ADULT PATIENTS:

- Patients 50-75 years old with high risk ALL in first CR (CR1) or ALL in CR >= second
CR (CR2)

- Patients >= 18 years old and < 50 years old with high risk ALL in CR1 who are not
eligible for a conventional allogeneic transplantation based on general medical
condition

- Patients >= 18 years old and < 50 years old with high risk ALL in CR1 who refuse a
conventional allogeneic transplant

- Patients >= 18 years old and < 50 years old with ALL in CR >= CR2 who are not
eligible for a conventional allogeneic transplantation based on general medical
condition

- Patients >= 18 years old and < 50 years old with high risk ALL in CR >= CR2 who
refuse a conventional allogeneic transplant

- CR is defined as < 5% blasts by morphology on a bone marrow aspirate and the absence
of peripheral blasts

- High risk adult ALL in CR1 includes those patients with one or more of the following:

- Age >=30 years

- Non T-cell phenotype

- Cytogenetic abnormalities including t(9;22), t(4;11), trisomy 8, or monosomy 7

- Failure to achieve CR after 4 weeks of induction chemotherapy

- PEDIATRIC PATIENTS:

- Patients < 18 years old with ALL in high risk CR1 who are not candidates for
conventional allogeneic transplantation based on general medical condition

- Patients < 18 years old with ALL in CR >= CR2 who are not candidates for conventional
allogeneic transplantation based on general medical condition

- Patients < 12 years old require approval by the Fred Hutchinson Cancer Research
Center (FHCRC) principal investigator prior to enrollment

- CR is defined as < 5% blasts by morphology on a bone marrow aspirate and absence of
peripheral blasts

- High risk pediatric ALL in CR1 includes those patients with one or more of the
following:

- Cytogenetic abnormalities including:

- t(9;22) with a white blood cell (WBC) >= 25,000 at diagnosis or

- t(4;11) in patients < 1 year old and >= 10 years old or

- Hypodiploidy (< 45 chromosomes)

- Failure to achieve CR after 4 weeks of induction chemotherapy

- Persistent peripheral blasts after one week of induction chemotherapy

- DONOR: FHCRC matching Grade 2.1: Unrelated donors who are prospectively:

- Matched for human leukocyte antigen (HLA)-DRB1 and DQB1 alleles (must be defined
by high resolution typing) and

- Only a single allele disparity will be allowed for HLA-A, B, or C as defined by
high resolution typing

- DONOR: A positive anti-donor cytotoxic crossmatch is an absolute donor exclusion;
donors are excluded when preexisting immunoreactivity is identified that would
jeopardize donor hematopoietic cell engraftment; this determination is based on the
standard practice of the individual institution; the recommended procedure for
patients with 10 of 10 HLA allele level (phenotypic) match is to obtain a panel
reactive antibody (PRA) screens to class I and class II antigens for all patients
before hematopoietic cell transplantation (HCT); if the PRA shows > 10% activity,
then flow cytometric or B and T cell cytotoxic cross matches should be obtained; the
donor should be excluded if any of the cytotoxic cross match assays are positive; for
those patients with an HLA class I allele mismatch, flow cytometric or B and T cell
cytotoxic cross matches should be obtained regardless of the PRA results

- DONOR: Patient and donor pairs homozygous at a mismatched allele are considered a
two-allele mismatch, i.e., the patient is A*0101 and the donor is A*0102, and this
type of mismatch is not allowed

- DONOR: Donor must consent to peripheral blood stem cell (PBSC) mobilization with
filgrastim (G-CSF) arranged through the National Marrow Donor Program (NMDP) or other
donor centers

Exclusion Criteria:

- Active central nervous system (CNS) disease

- Presence of circulating leukemic blasts (in the peripheral blood) detected by
standard pathology

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

- Pregnancy or breastfeeding

- Human immunodeficiency virus (HIV) seropositivity

- ORGAN DYSFUNCTION, ADULT CRITERIA:

- Requiring supplementary continuous oxygen OR diffusing capacity of the lung for
carbon monoxide (DLCO) < 40%

- Cardiac ejection fraction < 35%

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

- Karnofsky performance score < 50

- ORGAN DYSFUNCTION, PEDIATRIC CRITERIA:

- Lansky play-performance score < 40

- Patients with active non-hematologic malignancies (except non-melanoma skin cancers)

- Patients with a history of non-hematologic malignancies (except non-melanoma skin
cancers) currently in a complete remission, who are less than 5 years from the time
of complete remission, and have a > 20% risk of disease recurrence

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Leukemia-free survival

Outcome Description:

Incidence of survival without relapse. Kaplan-Meier estimates will be used to estimate one-year leukemia-free survival.

Outcome Time Frame:

1 year

Safety Issue:

No

Principal Investigator

George Georges

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Federal Government

Study ID:

1623.00

NCT ID:

NCT00031655

Start Date:

September 2001

Completion Date:

November 2012

Related Keywords:

  • Adult Acute Lymphoblastic Leukemia in Remission
  • Childhood Acute Lymphoblastic Leukemia in Remission
  • Recurrent Adult Acute Lymphoblastic Leukemia
  • Recurrent Childhood Acute Lymphoblastic Leukemia
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma

Name

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109
Oregon Health and Sciences UniversityPortland, Oregon  
Veterans Affairs Puget Sound Healthcare SystemSeattle, Washington  98108