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

Conditions:Blood Cancer, Lymphoma, Leukemia
Therapuetic Areas:Oncology
Age Range:Any
Start Date:March 2006

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A Myeloablative Conditioning Regimen Consisting of Cyclophosphamide, Fludarabine and Total Body Irradiation Followed by the Transplantation of Unrelated Donor Double Unit Umbilical Cord Blood Grafts for Patients With Hematological Malignancy

RATIONALE: Giving high-dose chemotherapy and total-body irradiation before a donor umbilical
cord blood stem cell transplant helps stop the growth of cancer or 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 before transplant may stop this from

PURPOSE: This phase II trial is studying how well giving cyclophosphamide and fludarabine
together with total-body irradiation and donor umbilical cord blood transplant works in
treating patients with hematologic cancer or other disease.



- Determine, preliminarily, the efficacy of double-unit umbilical cord blood (UCB)
transplantation (UCBT) in patients with hematologic malignancy.


- Determine the incidence and rate of donor-derived neutrophil and platelet recovery in
these patients.

- Determine the contribution of each unit of UCB to initial and sustained engraftment in
these patients.

- Determine the incidence and severity of acute graft-vs-host disease (GVHD) at 100 days
in these patients.

- Determine the incidence and severity of chronic GVHD at 1 year in these patients.

- Determine the incidence of treatment-related mortality at 100 and 180 days in these

- Determine the incidence of malignant relapse in these patients.

- Determine the incidence of serious infectious complications in these patients.

- Determine immune recovery after UCBT and correlate with serious infectious
complications in these patients.

- Determine the probabilities of overall and disease-free survival of these patients at 2
years after UCBT.

- Determine the performance of double-unit correlative laboratory studies and correlate
with engraftment of each unit in these patients.


- Myeloablative preparative regimen: Patients receive fludarabine phosphate IV over 30
minutes on days -7 to -5 and cyclophosphamide IV over 30-60 minutes on days -6 and -5.
Patients also undergo total-body irradiation 3 times daily on days -3 to -1 and twice
on day 0.

- Umbilical cord blood (UCB) transplantation: Patients receive UCB IV over 20-60 minutes
on day 0. Patients also receive filgrastim (G-CSF) IV or subcutaneously beginning on
day 1 and continuing until blood counts recover.

- Graft-vs-host (GVHD) prophylaxis: Patients receive cyclosporine IV over 2-4 hours or
orally every 8-12 hours on days -3 to 100 and mycophenolate mofetil IV or orally twice
daily on days -3 to 45.

Blood samples and bone marrow aspirates are collected at baseline and periodically during
and after completion of study treatment. Samples may be examined for engraftment, chimerism
analysis, cytogenetic analysis, recovery of natural killer cells, and immune recovery.
Lymphoid immunophenotyping and function is also determined.

UCB units are examined by flow cytometry and killer immunoglobulin-like receptor (KIR)
genotype analysis.

After completion of study therapy, patients are followed periodically for at least 2 years.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.


- Diagnosis of one of the following:

- Acute myeloid leukemia (AML) meeting 1 of the following criteria:

- Complete first remission (CR1) at high risk for relapse, defined by 1 of
the following:

- Known prior diagnosis of myelodysplastic syndromes (MDS)

- Therapy-related AML

- WBC > 100,000/mm³

- Presence of extramedullary leukemia at diagnosis

- Unfavorable FAB type (M0, M5-7)

- High-risk cytogenetics (those associated with MDS, abnormalities of
Philadelphia chromosomes 5, 7, or 8, or complex karyotype)

- Required ≥ 2 inductions to achieve CR1

- Complete second remission (CR2)

- No AML ≥ CR2

- Acute lymphoblastic leukemia (ALL) meeting 1 of the following criteria:

- CR1 at risk for relapse, defined by 1 of the following:

- WBC > 100,000/mm³ (< 18 years old) OR > 50,000/mm³ (≥ 18 years old)

- Presence of extensive extramedullary disease (excluding CNS disease)

- Presence of high-risk cytogenetic abnormality, such as t(9;22),
t(1;19), t(4;11), or other myelomonocytic leukemia rearrangements
(11q23) or t(8;14) (excluding blastic-phase ALL in pediatric patients)

- Failed to achieve complete remission after 4 weeks of induction

- CR2 or complete third remission (CR3)

- Not > CR3

- Acute undifferentiated leukemia, infant leukemia, or biphenotypic leukemia in
CR1, CR2, or CR3

- Patients with infant leukemia must be able to receive total-body

- Not > CR3

- Juvenile myelomonocytic leukemia with < 30% bone marrow blasts

- Chronic myelogenous leukemia meeting the following criteria:

- Failed prior imatinib mesylate AND in first or second chronic phase or
accelerated phase

- Not in blast crisis

- MDS meeting the following criteria:

- Low (score 0) International Prognostic Scoring System (IPSS) score with
life threatening cytopenia or red cell or platelet-transfusion dependent OR
intermediate (score 1) or high (score 2) IPSS score

- Patients with bone marrow blasts ≥ 10% should have AML induction therapy
with disease response to < 5% blasts and at least partial count recovery

- No MDS with ≥ 10% bone marrow blasts refractory to chemotherapy

- Non-Hodgkin's lymphoma (NHL) meeting 1 of the following criteria:

- High-grade disease in first partial remission (PR) after initial therapy
with biopsy-proven residual disease that is not appropriate for further
chemotherapy or autologous stem cell transplantation

- High-grade or diffuse large cell NHL with recurrent disease after first
remission with chemosensitivity as evidenced by at least PR (defined as >
50% reduction in mass size after therapy)

- No NHL refractory to chemotherapy (less than PR after ≥ 2 regimens)

- No AML evolved from myelofibrosis

- Not a candidate for autologous stem cell transplantation

- No active CNS leukemia

- No bone marrow aplasia (bone marrow cellularity < 5%)

- No acute leukemia with any of the following:

- Morphologic relapse or persistent disease in the bone marrow (cytogenetic
relapse without morphologic evidence of relapse or cytogenetic persistent
disease in the bone marrow is allowed)

- Active extramedullary leukemia

- Required > 2 courses of chemotherapy to obtain present remission status

- No suitably HLA matched related or unrelated volunteer donor available

- Double-unit umbilical cord blood units must meet the following criteria:

- At least 4 of 6 HLA-A and B antigen and DRB1 allele matched with recipient

- At least 3 of 6 HLA-A, B, and DRB1 matched to each other

- Cryopreserved dose of ≥ 1.5 x 10^7 total nucleated cells/recipient body weight
NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been
adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will
replace the former terminology of "low", "intermediate", or "high" grade
lymphoma. However, this protocol uses the former terminology.


- Karnofsky performance status (PS) 70-100% (age ≥ 16 years) OR Lansky PS 70-100% (age
< 16 years)

- Creatinine clearance ≥ 60 mL/min OR creatinine < 1.5 mg/dL

- Bilirubin < 2.5 mg/dL (unless Gilbert's syndrome)

- ALT and AST < 3 times upper limit of normal

- Albumin ≥ 2.5 g/dL

- LVEF ≥ 50%

- DLCO ≥ 60%

- No uncontrolled viral, bacterial, or fungal infection

- Not HIV positive

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception


- See Disease Characteristics

- No prior autologous or allogeneic hematopoietic stem cell transplantation

- No prior radiation therapy rendering the patient ineligible for total-body
We found this trial at
1275 York Avenue
New York, New York 10065
Memorial Sloan-Kettering Cancer Center Memorial Sloan-Kettering Cancer Center — the world's oldest and largest private...
New York, NY
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