Transplantation of Umbilical Cord Blood From Unrelated Donors in Patients With Hematological Diseases Using a Non-Myeloablative Preparative Regimen
N/A
69 Years
Both
Breast Cancer, Kidney Cancer, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes
Trial Information
Transplantation of Umbilical Cord Blood From Unrelated Donors in Patients With Hematological Diseases Using a Non-Myeloablative Preparative Regimen
OBJECTIVES:
Primary
- Determine the safety of nonmyeloablative preparative regimen comprising
cyclophosphamide, fludarabine, and total-body irradiation with or without
anti-thymocyte globulin, in terms of non-relapse mortality at day 100
post-transplantation, in patients with advanced hematologic malignancies, metastatic
breast cancer, or renal cell cancer who are undergoing umbilical cord blood
transplantation from an unrelated donor.
Secondary
- Determine the hematopoietic recovery and degree of chimerism on days 21, 60, 100, 180,
and 360 post-transplantation.
- Determine the incidence of grade II-IV and III-IV acute graft-versus-host disease
(GVHD) by day 100 post-transplantation and chronic GVHD at 1 year post-transplantation.
- Evaluate the risk of relapse at 1 year post-transplantation.
- Determine overall survival at 1 year post-transplantation.
OUTLINE:
- Nonmyeloablative preparative regimen: Patients receive cyclophosphamide IV over 2 hours
on day -6 and fludarabine IV over 1 hour on days -6 to -2. Patients also undergo
total-body irradiation on day -1. Some patients* may also receive anti-thymocyte
globulin (ATG) IV twice daily on days -6 to -4.
NOTE: *Patients who have not had prior combination chemotherapy within the past 3 months OR
who only received 1 prior induction course for the treatment of acute lymphoblastic
leukemia, acute myeloid leukemia, myelodysplastic syndromes, or chronic myelogenous leukemia
in blast crisis receive ATG during the preparative regimen.
- Umbilical cord blood transplantation (UCBT): Patients undergo UCBT from an unrelated
donor on day 0.
- Graft-versus-host disease prophylaxis: Patients receive cyclosporine IV over 2 hours or
orally 2-3 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 twice
daily beginning on day -3 and continuing until day 30 or until 7 days after
engraftment.
After transplantation, patients are followed periodically for 2 years.
PROJECTED ACCRUAL: A total of 120 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of 1 of the following:
- Acute myeloid leukemia (AML), meeting 1 of the following criteria:
- In first complete remission (CR1) by morphology AND at high risk, as
evidenced by 1 of the following:
- AML secondary to myelodysplastic syndromes (MDS)
- High-risk cytogenetics, such as those associated with MDS or complex
karyotype
- More than 2 courses of therap were required to obtain a CR
- In second or greater CR by morphology
- In morphologic relapse or persistent disease, defined as > 5% blasts in
normocellular bone marrow OR any percentage of blasts if blasts have unique
morphologic markers (e.g., auer rods)
- In cytogenetic relapse (without morphologic relapse)
- Acute lymphoblastic leukemia (ALL), meeting 1 of the following criteria:
- In CR1 by morphology AND at high risk, as evidenced by 1 of the following:
- High-risk cytogenetics, such as t(9;22), t(1;19), t(4;11), or other
MLL rearrangements
- More than 1 course of therapy was required to obtain a CR
- In second or greater CR by morphology
- In morphologic relapse or persistent disease as defined for AML
- In cytogenetic relapse (without morphologic relapse)
- Chronic myelogenous leukemia
- All types allowed except refractory blast crisis
- Non-Hodgkin's lymphoma (NHL)
- No intermediate- or high-grade NHL or mantle cell NHL that is progressive
on salvage therapy
- Stable disease allowed provided it is non-bulky
- Hodgkin's lymphoma
- No progressive disease on salvage therapy
- Stable disease allowed provided it is non-bulky
- Chronic lymphocytic leukemia
- Multiple myeloma
- MDS
- Any subtype allowed, including refractory anemia if there is severe
pancytopenia or complex cytogenetics
- Less than 5% blasts
- If patient has blasts ≥ 5% then they must undergo induction therapy
before transplantation
- Metastatic breast cancer
- Disease must have responded to recent chemotherapy OR in plateau after
response to chemotherapy
- Renal cell cancer
- Acquired bone marrow failure syndromes
- Small percentage of blasts that is equivocal between marrow regeneration vs early
relapse allowed provided there are no associated cytogenetic markers consistent with
relapse (for patients with AML or ALL)
- Must have a 4/6 HLA-A, -B, and -DRB1 matched unrelated umbilical cord blood donor
available
- No 5/6 or 6/6 HLA-A , -B, and -DRB1 matched sibling donor available
- No more than 2 antigen mismatches at the HLA-A, -B, or -DRB1 loci 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.
PATIENT CHARACTERISTICS:
- Karnofsky performance status 60-100% OR Lansky performance status 50-100% (pediatric
patients)
- Albumin > 2.5 g/dL
- Creatinine ≤ 2.0 mg/dL (adults) OR creatinine clearance > 40 mL/min (pediatric
patients)
- Adults with creatinine > 1.2 mg/dL or a history of renal dysfunction must have a
creatinine clearance > 40 mL/min
- Transaminases < 5 times upper limit of normal (ULN)
- Bilirubin < 3 times ULN
- LVEF ≥ 35%
- DLCO > 30% of predicted
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No evidence of HIV infection or known HIV-positivity
- No decompensated congestive heart failure
- No uncontrolled cardiac arrhythmia
- No requirement for supplemental oxygen
- No active, serious infection
- Recent mold infection (e.g., Aspergillus) allowed provided patient has received
≥ 30 days of appropriate treatment AND infection is controlled and cleared by an
infectious disease specialist
PRIOR CONCURRENT THERAPY:
- No prior irradiation that precludes the safe administration of 1 additional dose of
200 cGy of total-body irradiation
- At least 3 months since prior myeloablative bone marrow transplantation
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Safety as assessed by a non-relapse mortality < 30% within day 100
Safety Issue:
Yes
Principal Investigator
Claudio G. Brunstein, MD, PhD
Investigator Role:
Study Chair
Investigator Affiliation:
Masonic Cancer Center, University of Minnesota
Authority:
United States: Federal Government
Study ID:
2000LS039
NCT ID:
NCT00365287
Start Date:
June 2000
Completion Date:
December 2005
Related Keywords:
- Breast Cancer
- Kidney Cancer
- Leukemia
- Lymphoma
- Multiple Myeloma and Plasma Cell Neoplasm
- Myelodysplastic Syndromes
- stage IV breast cancer
- recurrent renal cell cancer
- stage III renal cell cancer
- stage IV renal cell cancer
- adult acute myeloid leukemia in remission
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities
- adult acute myeloid leukemia with inv(16)(p13;q22)
- adult acute myeloid leukemia with t(15;17)(q22;q12)
- adult acute myeloid leukemia with t(16;16)(p13;q22)
- adult acute myeloid leukemia with t(8;21)(q22;q22)
- recurrent adult acute myeloid leukemia
- recurrent childhood acute myeloid leukemia
- accelerated phase chronic myelogenous leukemia
- chronic phase chronic myelogenous leukemia
- relapsing chronic myelogenous leukemia
- recurrent adult Hodgkin lymphoma
- recurrent/refractory childhood Hodgkin lymphoma
- stage III adult Hodgkin lymphoma
- stage IV adult Hodgkin lymphoma
- stage III chronic lymphocytic leukemia
- stage IV chronic lymphocytic leukemia
- stage I multiple myeloma
- stage II multiple myeloma
- stage III multiple myeloma
- de novo myelodysplastic syndromes
- previously treated myelodysplastic syndromes
- secondary myelodysplastic syndromes
- refractory anemia
- adult acute lymphoblastic leukemia in remission
- blastic phase chronic myelogenous leukemia
- childhood acute lymphoblastic leukemia in remission
- childhood acute myeloid leukemia in remission
- childhood chronic myelogenous leukemia
- extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
- nodal marginal zone B-cell lymphoma
- noncontiguous stage II adult Burkitt lymphoma
- noncontiguous stage II adult diffuse large cell lymphoma
- noncontiguous stage II adult diffuse mixed cell lymphoma
- noncontiguous stage II adult diffuse small cleaved cell lymphoma
- noncontiguous stage II adult immunoblastic large cell lymphoma
- noncontiguous stage II adult lymphoblastic lymphoma
- noncontiguous stage II grade 1 follicular lymphoma
- noncontiguous stage II grade 2 follicular lymphoma
- noncontiguous stage II grade 3 follicular lymphoma
- noncontiguous stage II mantle cell lymphoma
- noncontiguous stage II marginal zone lymphoma
- noncontiguous stage II small lymphocytic lymphoma
- recurrent adult acute lymphoblastic leukemia
- recurrent adult Burkitt lymphoma
- recurrent adult diffuse large cell lymphoma
- recurrent adult diffuse mixed cell lymphoma
- recurrent adult diffuse small cleaved cell lymphoma
- recurrent adult immunoblastic large cell lymphoma
- recurrent adult lymphoblastic lymphoma
- recurrent childhood acute lymphoblastic leukemia
- recurrent childhood lymphoblastic lymphoma
- recurrent childhood large cell lymphoma
- recurrent childhood small noncleaved cell lymphoma
- recurrent grade 1 follicular lymphoma
- recurrent grade 2 follicular lymphoma
- recurrent grade 3 follicular lymphoma
- recurrent mantle cell lymphoma
- recurrent marginal zone lymphoma
- recurrent small lymphocytic lymphoma
- refractory chronic lymphocytic leukemia
- refractory multiple myeloma
- secondary acute myeloid leukemia
- splenic marginal zone lymphoma
- stage III adult Burkitt lymphoma
- stage III adult diffuse large cell lymphoma
- stage III adult diffuse mixed cell lymphoma
- stage III adult diffuse small cleaved cell lymphoma
- stage III adult immunoblastic large cell lymphoma
- stage III adult lymphoblastic lymphoma
- stage III grade 1 follicular lymphoma
- stage III grade 2 follicular lymphoma
- stage III grade 3 follicular lymphoma
- stage III mantle cell lymphoma
- stage III marginal zone lymphoma
- stage III small lymphocytic lymphoma
- stage IV adult Burkitt lymphoma
- stage IV adult diffuse large cell lymphoma
- stage IV adult diffuse mixed cell lymphoma
- stage IV adult diffuse small cleaved cell lymphoma
- stage IV adult immunoblastic large cell lymphoma
- stage IV adult lymphoblastic lymphoma
- stage IV grade 1 follicular lymphoma
- stage IV grade 2 follicular lymphoma
- stage IV grade 3 follicular lymphoma
- stage IV mantle cell lymphoma
- stage IV marginal zone lymphoma
- stage IV small lymphocytic lymphoma
- refractory anemia with excess blasts in transformation
- refractory anemia with ringed sideroblasts
- refractory cytopenia with multilineage dysplasia
- refractory anemia with excess blasts
- childhood myelodysplastic syndromes
- Breast Neoplasms
- Neoplasms
- Carcinoma, Renal Cell
- Kidney Neoplasms
- Hematologic Diseases
- Leukemia
- Lymphoma
- Lymphoma, Non-Hodgkin
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
- Myelodysplastic Syndromes
- Preleukemia
- Lymphoma, Large-Cell, Immunoblastic
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