Treatment of Hematologic Malignancies With High-Dose Chemo-Radiotherapy Followed by Single-Unit or Double-Unit Cord Blood Transplantation: A Phase II Study

Colorado Blood Cancer Institute1 site in 1 country20 target enrollmentNovember 2005

ConditionsAcute Myeloid Leukemia Acute Lymphoblastic Leukemia Chronic Myeloid Leukemia Non-Hodgkin Lymphoma Myelodysplastic Syndromes

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Acute Myeloid Leukemia
Sponsor: Colorado Blood Cancer Institute
Enrollment: 20
Locations: 1
Primary Endpoint: Evaluate the incidence of neutrophil engraftment after transplantation of one or two cord blood units
Last Updated: 19 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to evaluate the incidence of neutrophil engraftment after transplantation of one or two cord blood units meeting a predetermined total minimum cell dose of 2.0 x 10 to the seventh total nucleated cell (TNC)/kg.

Detailed Description

This is a non-randomized, phase II protocol to evaluate engraftment of cord blood after treatment with myeloablative conditioning of fludarabine, total body irradiation and cyclophosphamide. All patients will receive tacrolimus and mycophenolate mofetil as prophylaxis for graft-vs-host disease. Conditioning Regimen: * Days -10 to -7: Fludarabine 30mg/m2/day IV * Days -7 to -4: TBI 165 centigray BID * Days -3 to -2: Cyclophosphamide 40mg/kg/day IV Day 0: Infusion of Cord Blood Cells Graft-vs-Host Disease Prophylaxis * Day -1: Start tacrolimus 0.03mg/kg/day IV * Day 0: Start MMF 7.5mg/kg IV BID

Registry

clinicaltrials.gov

Start Date

November 2005

End Date

TBD

Last Updated

19 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Colorado Blood Cancer Institute

Eligibility Criteria

Inclusion Criteria

•Patients must:
•Be between the ages of 18 and 49 years inclusive.
•Have histologically proven hematologic malignancy and must meet accepted indications for allogeneic stem cell transplantation:
•Acute myeloid leukemia (AML): high-risk in first complete remission (CR), near first CR (\< 20% marrow blasts after induction therapy), or beyond first remission.
•Acute lymphoblastic leukemia with high-risk features in first remission (Philadelphia chromosome positive or other similar high-risk features), near first CR (\< 20% marrow blasts after induction therapy), or beyond first remission.
•Chronic myeloid leukemia: in chronic phase (CP) and have failed Gleevec or are intolerant and have signs of failing other treatments, or have history of accelerated or blast phases. Storage of autologous peripheral blood stem cells is recommended for this group for patients, particularly if in chronic phase.
•Non-Hodgkin's lymphoma: aggressive histology with relapsed or primary refractory disease and not eligible for autologous transplantation. Patients with low-grade histology must have either failed 2 or more lines of systemic chemotherapy including one rituximab-based regimen. Radioimmunotherapy will be considered the equivalent of one line of chemotherapy. Excluded if prior radiotherapy to chest or prior autologous transplantation.
•Myelodysplastic syndromes with International Prognostic Scoring System (IPSS) score of 1.5 or greater.
•Other hematological malignancies if approved by the pipeline meeting on a case by case basis. Must also be approved by principal investigator.
•Have no HLA-matched or 1-antigen mismatched related donors and no HLA-matched unrelated stem cell donors, or delays involved in performing a search are likely to be detrimental to the patient.

Exclusion Criteria

•Patients are ineligible for this protocol if they:
•Have a co-morbid medical condition, a psychiatric condition, or organ dysfunction that makes them at high-risk for treatment failure, for failed medical compliance, or for regimen-related toxicity from high-dose therapy.
•Patients with any of the following will be excluded:
•Pulmonary: hemoglobin (Hb)-adjusted diffusing capacity of lung for carbon monoxide (DLCO) \< 60%, forced expiratory volume in 1 second (FEV1) \< 70% of predicted, or receive continuous supplemental oxygen;
•Cardiac: left ventricular ejection fraction (LVEF) \< 50% or on any treatment for congestive heart failure;
•Renal: serum creatinine greater than 2.0 or calculated creatinine clearance \< 50 cc/min;
•Liver: ALT, AST, or serum bilirubin \> 1.5 x upper limit of normal (ULN). Any patient with elevated transaminases should have careful evaluation for the cause and liver biopsy may be required by the principle investigator. An elevated alkaline phosphatase should be fractionated and, if of liver origin, should be evaluated as for transaminases.
•Are female and are pregnant, lactating, or have a positive pregnancy test.
•Have a history of previous malignancy except for non-melanoma skin cancer and in-situ carcinoma of the cervix, unless the patient has been progression-free for \> 5 years
•Are HIV positive

Outcomes

Primary Outcomes

Evaluate the incidence of neutrophil engraftment after transplantation of one or two cord blood units

Secondary Outcomes

Evaluate safety as measured by day 100 treatment related mortality
Evaluate incidence of platelet engraftment
Evaluate incidences of acute and chronic graft-versus-host disease (GVHD)
Evaluate efficacy as measured by survival at 1 and 2 years after transplant
Evaluate chimerism from double cord transplants to determine source of long term engraftment