Fludarabine, Cyclophosphamide, and Total-Body Irradiation in Treating Patients Who Are Undergoing an Umbilical Cord Blood Transplant for Hematologic Cancer

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Basic Trial Information

PhaseTypeAgeTrial IDs
Phase IITreatment55 and underMT2005-10
NCI-2010-01444, 2005LS043, UMN-2005LS043, UMN-BMT-MT2005-10, UMN-MT2005-10, UMN-0507M71475, NCT00309842

Trial Description

Summary

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

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. 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.

OUTLINE:

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.

Eligibility Criteria

Inclusion Criteria:

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

Advanced myelofibrosis

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

Myeloproliferative syndromes

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

Exclusion Criteria:

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
Claudio Brunstein, Principal Investigator

Trial Sites

U.S.A.

Minnesota
Minneapolis

University of Minnesota/Masonic Cancer Center

Claudio Brunstein
Ph: 612-624-0400
Email: bruns072@umn.edu

Claudio Brunstein
Principal Investigator

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.