Fludarabine, Cyclophosphamide, and Total-Body Irradiation in Treating Patients Who Are Undergoing an Umbilical Cord Blood Transplant for Hematologic Cancer
Basic Trial Information
|Phase II||Treatment||55 and under||MT2005-10|
NCI-2010-01444, 2005LS043, UMN-2005LS043, UMN-BMT-MT2005-10, UMN-MT2005-10, UMN-0507M71475, NCT00309842
TRIAL STATUS: Active
This phase II trial studies how well giving fludarabine phosphate and cyclophosphamide together with total-body irradiation works in treating patients who are undergoing an umbilical cord blood transplant for hematologic cancer. Giving chemotherapy drugs, such as fludarabine phosphate and cyclophosphamide, and total-body irradiation before a donor umbilical cord blood stem cell transplant helps stop the growth of cancer cells and prepares the patient's bone marrow for the 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 may stop this from happening.
Further Study Information
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).
I. Determine the incidence of transplant-related mortality (TRM) at 6 months after UCBT.
II. Evaluate pattern of chimerism after double UCBT.
III. Determine incidence of neutrophil engraftment at day 42 after UCBT.
IV. Determine the incidence of platelet engraftment at 1 year after UCBT.
V. Determine the incidence of acute graft-versus-host disease (GVHD) grade II-IV and grade III-IV at day 100 after UCBT.
VI. Determine the incidence of chronic GVHD at 1 year after UCBT.
VII. Determine the disease free survival at 1 and 2 years after UCBT.
VIII. Determine the incidence relapse at 1 and 2 years after UCBT.
Patients receive a conditioning regimen comprising fludarabine phosphate intravenously (IV) over 1 hour on days -8 to -6, and cyclophosphamide IV over 1 hour on days -7 and -6. Patients also undergo TBI twice daily on days -4 to -1. Patients then undergo 1 or 2 units of UCBT on day 0. Patients receive filgrastim IV once daily beginning on day 1 and continuing until blood counts recover.
Patients receive GVHD prophylaxis comprising cyclosporine IV over 2 hours 2 or 3 times daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. Patients also receive mycophenolate mofetil IV or orally (PO) 2 or 3 times a day beginning on day -3 and continuing until day 30 or 7 days after engraftment in the absence of acute GVHD.
After completion of study treatment, patients are followed up periodically for 2 years.
The unrelated cord blood donor(s) must be 4-6/6 human leukocyte antigen (HLA)-A, B, DRB1 matched with the recipient (HLA matching using molecular techniques: A and B to antigen level resolution and DR to allele level resolution)
No existing HLA-identical related donor is available
Suitable UCB units available according to Umbilical Cord Blood Graft selection algorithm; the UCB graft may consist of one or two UCB units
Acute myeloid leukemia (AML): high risk complete response (CR)1 (as evidenced by preceding myelodysplastic syndromes [MDS], high risk cytogenetics, >= 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia; CR2+; all patients must be in CR as defined by hematological recovery, AND < 5% blasts by light microscopy within the bone marrow with a cellularity of >=15%
Very high risk pediatric patients with AML; patients < 21 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 lymphocytic leukemia (ALL): high risk CR1 as defined by cytogentics (such as t(9;22), t (1:19), t(4;11), other mixed lineage leukemia (MLL) rearrangements, hypodiploidy, or IKZF1 abnormalities), deoxyribonucleic acid (DNA) index < 0.81, > 1 cycle to obtain CR or presence minimal residual disease (MRD); patients in CR2+ are eligible; all patients must be in CR as defined by hematological recovery, AND < 5% blasts by light microscopy within the bone marrow with a cellularity of >= 15%
Very high risk pediatric patients with ALL; patients < 21 years are also considered high risk CR1 if they had M2 or M3 marrow at day 42 from the initiation of induction or M3 marrow at the end of induction; they are eligible once they achieved a complete remission
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
Plasma Cell leukemia after initial therapy, who achieved at least a partial remission
Myelodysplasia (MDS) International Prostate Symptom Score (IPSS) Int-2 or High risk (i.e. refractory anemia with excess blasts [RAEB], refractory anemia with excess blasts in transformation [RAEBt]) or refractory anemia with severe pancytopenia or high risk cytogenetics; blasts must be < 10% by a representative bone marrow aspirate morphology
Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma or follicular lymphoma are eligible if there was disease progression/relapse within 12 of achieving a partial or complete remission; patients who had remissions lasting > 12 months, are eligible after at least two prior therapies; patients with bulky disease (nodal mass greater than 5 cm) should be considered for debulking chemotherapy before transplant
Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are eligible after initial therapy in CR1+ or PR1+
Large cell non-Hodgkin's lymphoma (NHL) > CR2/ > PR2; patients in CR2/PR2 with initial short remission (< 6 months) are eligible
Lymphoblastic lymphoma, Burkitt’s lymphoma, and other high-grade NHL after initial therapy if stage III/IV in CR1/PR1 or after progression if stage I/II < 1 year
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
Recipients must have a Karnofsky score (adults) >= 80 % or Lansky score >= 50% (pediatrics)
Creatinine < 2.0 (adults) or creatinine clearance > 40 ml/min (pediatrics)
Bilirubin, aspartate aminotransferase (AST)/alanine aminotransferase (ALT), alkaline phosphatase (ALP) =< 2 x upper limit of normal
Diffusion capacity of carbon monoxide (DLCO)corr > 50% normal
Left ventricular ejection fraction >= 45%
Voluntary written informed consent before performance of any study-related procedure not part of normal medical care
Active infection at time of transplantation (including active infection with aspergillus or other mold within 30 days)
History of human immunodeficiency virus (HIV) infection
Pregnant or breast feeding; the agents used in this study may be teratogenic to a fetus and there is no information on the excretion of agents into breast milk; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy
Chemotherapy refractory large cell and high grade NHL (i.e. progressive disease after > 2 salvage regimens)
If > 18 years old, prior myeloablative transplant within the last 6 months
If =< 18 years old, prior myeloablative transplant within the last 6 months; if > 18 years old prior myeloablative allotransplant or autologous transplant
Extensive prior therapy including > 12 months alkylator therapy or > 6 months alkylator therapy with extensive radiation
Patients who have received Y-90 ibritumomab (zevalin) or I-131 tostumomab (bexxar), as part of their salvage therapy are not eligible for myeloablative umbilical cord blood transplant
Trial Contact Information
Trial Lead Organizations / Sponsors / Collaborators
University of Minnesota/Masonic Cancer Center
- National Cancer Institute
University of Minnesota/Masonic Cancer Center
Link to the current ClinicalTrials.gov record.
NLM Identifier NCT00309842
Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.