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

STATUS

Recruiting
End date

Dec 1, 2025
participants needed

135
sponsor

Fred Hutchinson Cancer Center

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Updated on 7 October 2022

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cancer

hypertension

remission

chronic myeloid leukemia

myeloid leukemia

lymphoid leukemia

total body irradiation

fludarabine

blast crisis

anemia

mycophenolate mofetil

imatinib

cyclophosphamide

chronic lymphocytic leukemia

hla-a

lymphoma

myelofibrosis

multiple myeloma

hodgkin's disease

cyclosporine

acute leukemia

myelodysplasia

white blood cell count

umbilical cord blood transplantation

flow cytometry

lymphoblastic lymphoma

carbon monoxide

ejection fraction

waldenstrom's macroglobulinemia

residual disease

hepatitis

blood disorder

leukemia

bone marrow procedure

hematologic disorder

lymphocytic leukemia

transplant conditioning

thiotepa

residual tumor

autologous transplant

burkitt's lymphoma

serum bilirubin level

blast cells

white blood cells

chemotherapy regimen

autograft

prolymphocytic leukemia

follicular lymphoma

abnormal cells

raeb

cancer chemotherapy

b-cell lymphoma

mantle cell lymphoma

pancytopenia

mycophenolate

blood cell count

hematologic disorders

hematologic disease

nodal mass

acute biphenotypic leukemia

left ventricular fractional shortening

b-cell small lymphocytic lymphoma

Summary

This phase II trial studies how well giving an umbilical cord blood transplant together with cyclophosphamide, fludarabine, and total-body irradiation (TBI) works in treating patients with hematologic disease. Giving chemotherapy, such as cyclophosphamide and fludarabine, 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.

Description

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM I: Patients receive myeloablative conditioning comprising fludarabine intravenously (IV) over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 and -6, and undergo high-dose TBI twice daily (BID) on days -4 to -1. Patients then undergo single- or double-unit UCBT on day 0.

ARM II: Patients receive myeloablative conditioning comprising fludarabine IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 2-4 hours on days -5 and -4, and middle-intensity TBI once daily (QD) on days -2 and -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 0 to 7 and then PO (if tolerated) three times daily (TID) on days 8-30. Mycophenolate mofetil is tapered to BID on day 30 or 7 days after engraftment if there is no acute GVHD, and then tapered over 2-3 weeks beginning on day 45 (or 15 days after engraftment if engraftment occurred > day 30) after engraftment if there continues to be no evidence of acute GVHD.

After completion of study treatment, patients are followed up at 6 months, 1 year, and 2 years.

Details

Condition	Acute Biphenotypic Leukemia, Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Burkitt Lymphoma, Chronic Lymphocytic Leukemia, Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Follicular Lymphoma, Lymphoblastic Lymphoma, Lymphoplasmacytic Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma, Myelodysplastic Syndrome, Myelofibrosis, Non-Hodgkin Lymphoma, Plasma Cell Myeloma, Prolymphocytic Leukemia, Refractory Anemia, Small Lymphocytic Lymphoma
Treatment	cyclophosphamide, cyclosporine, fludarabine phosphate, mycophenolate mofetil, laboratory biomarker analysis, Fludarabine, Total-Body Irradiation, Umbilical Cord Blood Transplantation, thiotepa, Double-Unit Umbilical Cord Blood Transplantation
Clinical Study Identifier	NCT00719888
Sponsor	Fred Hutchinson Cancer Center
Last Modified on	7 October 2022

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Eligibility		Yes	No	Not Sure
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
	Age and Disease Criteria
	High-dose TBI regimen: 6 months to =< 45 years
	Middle-intensity TBI regimen: 6 months to =< 65 years
	Conditioning regimen selection should be based on the underlying disease, presence of minimum residual disease (MRD), age, co-morbidities, and attending physician
	Acute myeloid leukemia, including biphenotypic acute leukemia or mixed-lineage
	leukemia
	All patients must be in complete remission (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 who do not have high-risk features (for example preceding myelodysplastic syndrome [MDS], high-risk cytogenetics, >= 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia or >= CR2) must be discussed with the principal investigator (PI) prior to enrollment and at the Patient Care Conference or equivalent group such as the pediatric leukemia board as an alternative
	Patients in whom 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 PI prior to enrollment; patients persistently aplastic for greater than one month since completing last chemotherapy are also eligible with 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%
	Acute lymphoblastic leukemia, including biphenotypic acute leukemia or mixed-lineage
	leukemia
	blasts in marrow after having failed one or more cycles of chemotherapy; this
	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 who do not have high-risk disease (high risk CR1, greater than one cycle to obtain CR or >= CR2) must be discussed with the PI prior to enrollment and at the Patient Care Conference or equivalent group such as the pediatric leukemia board as an alternative
	group of patients will be analyzed separately
	Patients in whom 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 Ann Dahlberg prior to enrollment; patients persistently aplastic for greater than one month since completing last chemotherapy are also eligible with PI approval
	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 myelogenous leukemia excluding refractory blast crisis; to be eligible in
	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
	first chronic phase (CP1) patient must have failed or be intolerant to
	Mantle-cell lymphoma, prolymphocytic leukemia: Eligible after initial therapy in >= CR1 or >= PR1
	imatinib mesylate
	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
	Performance status score: Karnofsky (for adults) >= 70% or Eastern Cooperative Oncology Group (ECOG) 0-1 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 or a pediatric patient who is unable to perform pulmonary function tests (PFTs) but has adequate pulmonary function
	Multiple myeloma beyond PR2: Patients with chromosome 13 abnormalities, first response
	Left ventricular ejection fraction > 45% or shortening fraction > 26%
	lasting less than 6 months, or beta-2 microglobulin > 3 mg/L, may be
	considered for this protocol after initial therapy
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)
	Patients with history of prior myeloablative transplant containing full dose TBI (greater than 8 gray [Gy]) will not be eligible for Regimen A; however, they may still enroll on Regimen B if they otherwise meet inclusion and exclusion criteria
	Any prior myeloablative transplant within the last 6 months
	Patients >= 45 years: comorbidity score of 5 or higher
	Patients who have received Y-90 ibritumomab (Zevalin) or I-131 tostumomab (Bexxar), as part of their salvage therapy are not eligible for Regimen A

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cancer

hypertension

remission

chronic myeloid leukemia

myeloid leukemia

lymphoid leukemia

total body irradiation

fludarabine

blast crisis

anemia

mycophenolate mofetil

imatinib

cyclophosphamide

chronic lymphocytic leukemia

white blood cell count

umbilical cord blood transplantation

flow cytometry

lymphoblastic lymphoma

carbon monoxide

ejection fraction

waldenstrom's macroglobulinemia

bone marrow procedure

hematologic disorder

lymphocytic leukemia

transplant conditioning

thiotepa

residual tumor

autologous transplant

burkitt's lymphoma

serum bilirubin level

prolymphocytic leukemia

hematologic disorders

hematologic disease

nodal mass

acute biphenotypic leukemia

left ventricular fractional shortening

b-cell small lymphocytic lymphoma

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