Treatment of Hematologic Malignancies With Single-Unit or Double-Unit Cord Blood Transplantation

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00328237
• Other study ID #: RMBMT-149
• Status: Recruiting
• Phase: Phase 2
• First received: May 17, 2006
• Last updated: June 23, 2006
• Start date: November 2005

Study information

• Verified date: November 2005
• Source: Colorado Blood Cancer Institute
• Contact: Nicole Stephens, RN, BSN, OCN
• Phone: 303-336-2183
• Email: Nicole.Stephens[@]USOncology.com
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 49 Years

Eligibility

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.

• Have an ECOG performance status of 0 or 1 at the time of transplant.

• Have major end organs (heart, lungs, liver, and kidneys) assessed and deemed adequate to withstand the effects of high-dose therapy planned for this protocol.

• Have given voluntary informed consent.

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

• Refractory malignancy: acute leukemia with greater than 30% blasts in bone marrow unless with untreated first relapse of AML or untreated myelodysplastic syndrome evolved to AML.

• Acute leukemia with greater than 1000 blasts/ul in peripheral blood.

• Uncontrolled central nervous system (CNS) leukemia or lymphoma.

• Prior autologous or allogeneic transplantation using a myeloablative regimen.

• Uncontrolled hypertension (systolic blood pressure [SBP] > 140, diastolic blood pressure [DBP] > 90) or hypertension requiring > 2 drugs for good control (SBP < 130, DBP < 90).

• Invasive mold infection that is uncontrolled or has received less than one month of antifungal therapy.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Chronic Myeloid Leukemia
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Lymphoma, Non-Hodgkin
• Myelodysplastic Syndromes
• Non-Hodgkin Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia

Intervention

Procedure:
• Cord Blood Transplant

Locations

Country	Name	City	State
United States	Rocky Mountain Blood and Marrow Transplant Program	Denver	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
Colorado Blood Cancer Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate the incidence of neutrophil engraftment after transplantation of one or two cord blood units
Secondary	Evaluate safety as measured by day 100 treatment related mortality
Secondary	Evaluate incidence of platelet engraftment
Secondary	Evaluate incidences of acute and chronic graft-versus-host disease (GVHD)
Secondary	Evaluate efficacy as measured by survival at 1 and 2 years after transplant
Secondary	Evaluate chimerism from double cord transplants to determine source of long term engraftment