Umbilical Cord Blood Transplantation in Treating Patients With High-Risk Hematologic Cancer

Trial Information

A Pilot Study of Unrelated Umbilical Cord Blood Transplantation in Patients With High Risk Hematologic Malignancies

OBJECTIVES:

- Determine the rates of hematologic and immune reconstitution in patients with high risk
hematologic malignancies who are undergoing high dose chemoradiotherapy followed by
unrelated umbilical cord blood (UCB) transplantation.

- Determine the incidence of graft-versus-host-disease in this setting.

- Describe the incidence of recurrent disease in these patients post UCB transplant.

- Describe the incidence of serious infections and secondary lymphoproliferative diseases
following transplantation with UCB in these patients.

- Determine specifically whether larger recipients can be durably engrafted with
unrelated UCB, and determine whether nucleated cell or progenitor cell content of the
graft is predictive of hematological engraftment.

OUTLINE: Patients may undergo a back-up peripheral blood stem cell collection prior to
treatment.

Patients receive 9 fractions of total body irradiation (TBI) on days -9 to -5 followed by
melphalan IV for three days on days -4 to -2 and antithymocyte globulin IV or
methylprednisolone IV for three days on days -3 to -1. On day 0, patients receive umbilical
cord blood infusion. If TBI is not tolerated, busulfan is substituted and administered
orally every 6 hours for 4 days on days -8 to -5. Cyclosporine and methylprednisolone begin
on day -2 and continue for 6 months.

Patients are followed at least monthly for 1 year, then every 6 months for the second year,
and then annually thereafter.

PROJECTED ACCRUAL: There will be a maximum of 48 patients accrued into this study over 4
years.

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed high risk malignancy including:

- Acute nonlymphocytic leukemia (ANLL) after induction failure, or in first
complete remission with high risk features including stem cell or biphenotypic
classification (acute myeloid leukemia (AML) M0), erythroleukemia (AML M6),
acute megakaryocytic leukemia (AML M7), cytogenic markers indicative of poor
prognosis, or failure to achieve complete remission after standard induction
therapy

- Acute lymphocytic leukemia (ALL) or ANLL in second or subsequent remission

- Chronic myeloid leukemia (CML) in chronic phase

- CML with accelerated phase or blast crisis are eligible after reinduction
chemotherapy converts disease to chronic phase

- High risk ALL in first complete remission

- Myelodysplastic syndrome with evidence of evolution to acute myeloid leukemia

- Refractory anemia with excess blasts

- Refractory anemia with excess blasts in transformation

- Non-Hodgkin's lymphoma (NHL), ANLL, or ALL with recurrent disease after
autologous stem cell transplantation

- Must also meet all the following conditions:

- No HLA-ABC/DR identical related bone marrow or UCB donor

- No 5/6 antigen matched related bone marrow or UCB donor

- Condition precludes waiting to search and find a donor in the National Marrow
Donor Registry

- Must have an available serologic matched umbilical cord blood unit in the New York
Blood Center's Placental Blood Project

- No active CNS disease

PATIENT CHARACTERISTICS:

Age:

- Under 55 at time of umbilical cord blood transplantation

Performance status:

- Zubrod 0-1

- Karnofsky 80-100%

Life expectancy:

- At least 3 months

Hematopoietic:

- For patients with ALL or ANLL in remission, CML in chronic phase, or NHL without
marrow involvement who elect to undergo autologous peripheral blood stem cell
collection and storage:

- WBC at least 3,000/mm^3

- Absolute neutrophil count at least 1,000/mm^3

- Platelet count at least 100,000/mm^3

Hepatic:

- Bilirubin no greater than 2.0 mg/dL

- ALT/AST no greater than 4 times normal

Renal:

- Creatinine no greater than 2.0 mg/dL

- Creatinine clearance at least 50 mL/min

Cardiovascular:

- Normal cardiac function by echocardiogram or radionuclide scan (shortening fraction
or ejection fraction at least 80% of normal value for age)

Pulmonary:

- FVC and FEV_1 at least 60% of predicted for age

- For adults:

- DLCO at least 60% of predicted

Other:

- HIV negative

- No active infections at time of autologous stem cell harvest or pretransplant
cytoreduction

- Not pregnant or nursing

- Effective contraception required of all fertile patients

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- Prior autologous stem cell transplantation allowed

Chemotherapy:

- See Disease Characteristics

Endocrine therapy:

- Not specified

Radiotherapy:

- Not specified

Surgery:

- Not specified

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

rates of durable engraftment in patients

Outcome Description:

The primary study end point will be hematologic engraftment. Engraftment is defined as achieving ANC larger than or equal to 500 ul/mm3 of donor origin for three consecutive measurements on different days by day +42.

Outcome Time Frame:

day 42

Safety Issue:

Principal Investigator

Brenda W. Cooper, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

CWRU4Y97

NCT ID:

NCT00003335

Start Date:

January 1998

Completion Date:

January 2012

Related Keywords:

Graft Versus Host Disease
Leukemia
Lymphoma
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
recurrent childhood acute lymphoblastic leukemia
recurrent childhood lymphoblastic lymphoma
recurrent adult acute lymphoblastic leukemia
chronic phase chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
untreated childhood acute lymphoblastic leukemia
adult acute myeloid leukemia in remission
adult acute lymphoblastic leukemia in remission
childhood acute myeloid leukemia in remission
childhood acute lymphoblastic leukemia in remission
adult acute erythroid leukemia (M6)
adult acute megakaryoblastic leukemia (M7)
childhood acute erythroleukemia (M6)
childhood acute megakaryocytic leukemia (M7)
refractory anemia with excess blasts
refractory anemia with excess blasts in transformation
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
graft versus host disease
adult acute minimally differentiated myeloid leukemia (M0)
childhood acute minimally differentiated myeloid leukemia (M0)
recurrent childhood small noncleaved cell lymphoma
recurrent childhood large cell lymphoma
recurrent mantle cell lymphoma
childhood chronic myelogenous leukemia
atypical chronic myeloid leukemia
myelodysplastic/myeloproliferative disease, unclassifiable
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with t(15;17)(q22;q12)
childhood myelodysplastic syndromes
Graft vs Host Disease
Leukemia
Lymphoma
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases

Name	Location
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center	Cleveland, Ohio 44106-5065

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