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

Case Comprehensive Cancer Center (Case CCC)

Status and phase

Completed

Phase 2

Conditions

Graft Versus Host Disease

Lymphoma

Leukemia

Myelodysplastic/Myeloproliferative Diseases

Myelodysplastic Syndromes

Treatments

Drug: melphalan

Radiation: radiation therapy

Procedure: umbilical cord blood transplantation

Drug: methylprednisolone

Drug: cyclosporine

Drug: busulfan

Biological: anti-thymocyte globulin

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00003335

P30CA043703 (U.S. NIH Grant/Contract)

CWRU4Y97 (Other Identifier)

NCI-G98-1429

Details and patient eligibility

About

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.

Full 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.

Enrollment

44 patients

Sex

All

Ages

Under 54 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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: