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

Sponsor

Case Comprehensive Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00003335

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

168

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Umbilical cord blood transplantation may allow doctors to give higher doses of chemotherapy or radiation therapy and kill more cancer cells.

PURPOSE: This phase II trial is studying allogeneic umbilical cord blood transplantation to see how well it works when given with chemotherapy or radiation therapy in treating patients with high-risk hematologic cancer.

Condition or Disease	Intervention/Treatment	Phase
Graft Versus Host Disease Leukemia Lymphoma Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases	Biological: anti-thymocyte globulin Drug: busulfan Drug: cyclosporine Drug: melphalan Drug: methylprednisolone Procedure: umbilical cord blood transplantation Radiation: radiation therapy	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

44 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jan 1, 1998

Actual Primary Completion Date :

Nov 1, 2007

Actual Study Completion Date :

Jan 1, 2012

Outcome Measures

Primary Outcome Measures

rates of durable engraftment in patients [day 42]
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.

Secondary Outcome Measures

Event-free survival by clinical and pathological disease assessment [at disease progression or death]
incidence of recurrent disease in patients post UCB transplant [post transplant]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 54 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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