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Umbilical Cord Blood Transplant, Cyclophosphamide, Fludarabine Phosphate, and Total-Body Irradiation in Treating Patients With Hematologic Disease

Information source: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia in Remission; Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Aggressive Non-Hodgkin Lymphoma; B Acute Lymphoblastic Leukemia With t(1;19)(q23;p13.3); E2A-PBX1 (TCF3-PBX1); Burkitt Lymphoma; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Lymphoblastic Lymphoma; Mantle Cell Lymphoma; Myelofibrosis; Pancytopenia; Plasma Cell Myeloma; Prolymphocytic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Recurrent Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Anemia With Excess Blasts

Intervention: Cyclophosphamide (Drug); Cyclosporine (Drug); Double-Unit Umbilical Cord Blood Transplantation (Procedure); Fludarabine Phosphate (Drug); Laboratory Biomarker Analysis (Other); Mycophenolate Mofetil (Drug); Total-Body Irradiation (Radiation); Umbilical Cord Blood Transplantation (Procedure)

Phase: Phase 2

Status: Recruiting

Sponsored by: Fred Hutchinson Cancer Research Center

Official(s) and/or principal investigator(s):
Colleen Delaney, Principal Investigator, Affiliation: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Summary

This phase II trial studies how well giving an umbilical cord blood transplant together with cyclophosphamide (CY), fludarabine phosphate (FLU), and total-body irradiation (TBI) works in treating patients with hematologic disease. Giving chemotherapy, such as CY and FLU, and TBI before a donor umbilical cord blood transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after transplant may stop this from happening.

Clinical Details

Official title: Transplantation of Umbilical Cord Blood for Patients With Hematological Diseases With Cyclophosphamide/Fludarabine/Total Body Irradiation Myeloablative Preparative Regimen

Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Overall survival

Secondary outcome:

Chimerism analysis

Incidence of chronic GVHD

Incidence of clinically significant infections

Incidence of grade II-IV and III-IV acute GVHD

Incidence of neutrophil engraftment

Incidence of platelet recovery

Incidence of relapse

Incidence of transplant-related mortality

Progression-free survival

Detailed description: PRIMARY OBJECTIVES: I. To determine the one year survival of patients undergoing umbilical cord blood transplantation (UCBT) after a myeloablative preparative regimen consisting of cyclophosphamide (CY), fludarabine (FLU), and fractionated total body irradiation (TBI). SECONDARY OBJECTIVES: I. Incidence of transplant-related mortality (TRM) at 6 months. II. Chimerism at multiple time points. III. Incidence of neutrophil engraftment at day 42. IV. Incidence of platelet engraftment 6 months. V. Incidence of acute graft-versus-host disease (GVHD) grade II-IV and grade III-IV at day 100. VI. Incidence of chronic GVHD at day 100, 1 year and 2 years. VII. Incidence of clinically significant infections at 6 months, 1 year and 2 years. VIII. Incidence of disease free survival at 1 and 2 years. IX. Incidence of relapse at 1 and 2 years. OUTLINE: Patients receive myeloablative conditioning comprising FLU intravenously (IV) over 30

minutes on days - 8 to -6, CY IV on days -7 and -6, and undergo TBI twice daily on days -4 to

- 1. Patients then undergo single- or double-unit UCBT on day 0.

Patients receive GVHD prophylaxis comprising cyclosporine IV over 1 hour every 8 or 12

hours, then cyclosporine orally (PO) (if tolerated), on days - 3 to 100 with taper on day

101. Patients also receive mycophenolate mofetil IV every 8 hours on days - 3 to 5 and then

mycophenolate mofetil PO (if tolerated) on days 6-30. Mycophenolate mofetil is discontinued on day 30 or 7 days after engraftment if there is no acute GVHD. After completion of study treatment, patients are followed up at 6 months, 1 year, and 2 years.

Eligibility

Minimum age: 6 Months. Maximum age: 45 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- GRAFT CRITERIA:

- UCB units will be selected according to current umbilical cord blood graft

selection algorithm; one or 2 UCB units may be used to achieve the required cell dose

- The UCB graft is matched at 4-6 human leukocyte antigen (HLA)-A, B, DRB1

antigens with the recipient; this may include 0-2 antigen mismatches at the A or B or DRB1 loci; unit selection based on cryopreserved nucleated cell dose and HLA-A,B, DRB1 using intermediate resolution A, B antigen and DRB1 allele typing

- If 2 UCB units are required to reach the target cell dose, each unit must be a

4-6 antigen match to the recipient

- Acute myeloid leukemia:

- High risk first complete remission (CR1) as evidenced by preceding

myelodysplastic syndromes (MDS), high risk cytogenetics (for example, monosomy 5 or 7), or high risk (HR) as defined by referring institution treatment protocol, >= 2 cycles to obtain complete response (CR), erythroblastic or megakaryocytic leukemia; >= second complete remission (CR2)

- All patients must be in CR as defined by hematologic recovery and < 5% blasts by

morphology/flow cytometry in a representative bone marrow sample with cellularity >= 15% for age

- Patients in which adequate marrow/biopsy specimens cannot be obtained to

determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry, recovery of peripheral blood counts with no circulating blasts, and/or normal cytogenetics (if applicable) may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures; these patients must be discussed with the principal investigator, Colleen Delaney prior to enrollment; patients persistently aplastic for greater than one month since completing last chemotherapy are also eligible with principal investigator (PI) approval

- Very high risk pediatric/young adult patients with acute myeloid leukemia (AML):

Patients =< 25 years, however, are eligible with (M2 marrow) with =< 25% blasts in marrow after having failed one or more cycles of chemotherapy; this group of patients will be analyzed separately

- Acute lymphoblastic leukemia:

- High risk CR1 [for example, but not limited to: t(9;22), t(1;19), t(4;11) or

other mixed lineage leukemia (MLL) rearrangements, hypodiploid]

- Greater than 1 cycle to obtain CR; >= CR2

- All patients must be in CR as defined by < 5% blasts by morphology/flow

cytometry in a representative bone marrow sample with cellularity >= 15% for age

- Patients in which adequate marrow/biopsy specimens cannot be obtained to

determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry, recovery of peripheral blood counts with no circulating blasts, and/or normal cytogenetics (if applicable) may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures; these patients must be discussed with the principal investigator, Colleen Delaney prior to enrollment; patients persistently aplastic for greater than one month since completing last chemotherapy are also eligible with PI approval

- Chronic myelogenous leukemia excluding refractory blast crisis; to be eligible in

first chronic phase (CP1) patient must have failed or be intolerant to imatinib mesylate

- Advanced myelofibrosis

- Myelodysplasia (MDS) International Prognostic Scoring System (IPSS) intermediate

(Int)-2 or high risk (i. e., refractory anemia with excess blasts [RAEB], RAEB in transformation [RAEBt]) or refractory anemia with severe pancytopenia or high risk cytogenetics; blasts must be < 10% by a representative bone marrow aspirate morphology

- Lymphoblastic lymphoma, Burkitt's lymphoma, and other high-grade non-Hodgkin lymphoma

(NHL) after initial therapy if stage III/IV in first partial response (PR1) or after progression if stage I/II < 1 year; stage III/IV patients are eligible after progression in CR/PR

- Chronic lymphocytic leukemia /small lymphocytic lymphoma (CLL/SLL), marginal zone

B-cell lymphoma, lymphoplasmacytic lymphoma or follicular lymphoma that have progressed after at least two different prior therapies; patients with bulky disease (nodal mass greater than 5 cm) should be considered for debulking chemotherapy before transplant; these patients must be presented at primary care center (PCC) prior to enrollment, given potential competing eligibility on autotransplant protocols

- Mantle-cell lymphoma, prolymphocytic leukemia: Eligible after initial therapy in >=

CR1 or >= PR1

- Large cell NHL > CR2/> second partial response (PR2):

- Patients in CR2/PR2 with initial short remission (< 6 months) are eligible

- These patients must be presented at PCC prior to enrollment, given potential

competing eligibility on autotransplant protocols

- Multiple myeloma beyond PR2: Patients with chromosome 13 abnormalities, first

response lasting less than 6 months, or beta-2 microglobulin > 3 mg/L, may be considered for this protocol after initial therapy

- Performance status score: Karnofsky (for adults) >= 70% or Lansky (for children) >=

50%

- Creatinine < 2. 0 mg/dL (for adults) or creatinine clearance > 60 ml/min (for

children)

- Patients with clinical or laboratory evidence of liver disease will be evaluated for

the cause of liver disease, its clinical severity in terms of liver function, histology, and the degree of portal hypertension; patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease will be excluded

- Diffusion capacity for carbon monoxide corrected (DLCOcorr) > 50% normal

- Left ventricular ejection fraction > 45% or shortening fraction > 26%

Exclusion Criteria:

- Uncontrolled viral or bacterial infection at the time of study enrollment

- Active or recent (prior 6 month) invasive fungal infection without interdisciplinary

(ID) consult and approval

- History of human immunodeficiency virus (HIV) infection

- Pregnant or breastfeeding

- Chemotherapy refractory large cell and high grade NHL (i. e., progressive disease

after > 2 salvage regimens)

- Prior myeloablative transplant containing full dose TBI (greater than 8 Gray [Gy])

- Any prior myeloablative transplant within the last 6 months

- Patients who have received Y-90 ibritumomab (Zevalin) or I-131 tositumomab (Bexxar),

as part of their salvage therapy are not eligible for myeloablative umbilical cord blood transplant

Locations and Contacts

University of Colorado Cancer Center - Anschutz Cancer Pavilion, Aurora, Colorado 80045, United States; Completed

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium, Seattle, Washington 98109, United States; Recruiting
Colleen Delaney, Phone: 206-667-1385
Colleen Delaney, Principal Investigator

VA Puget Sound Health Care System, Seattle, Washington 98101, United States; Recruiting
Thomas R. Chauncey, Phone: 206-764-2199
Thomas R. Chauncey, Principal Investigator

Additional Information

Starting date: November 2005
Last updated: May 11, 2015

Page last updated: August 20, 2015

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