Non-Myeloablative Conditioning and Unrelated Umbilical Cord Blood Transplantation for Children and Adults With Serious Oncohematologic Diseases
N/A
75 Years
Both
Chronic Myeloproliferative Disorders, Graft Versus Host Disease, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms
Trial Information
Non-Myeloablative Conditioning and Unrelated Umbilical Cord Blood Transplantation for Children and Adults With Serious Oncohematologic Diseases
OBJECTIVES:
- Determine the frequency, extent, and rate of donor (myeloid and lymphoid) engraftment
in patients with serious hematologic malignancies treated with nonmyeloablative
conditioning regimen comprising fludarabine, cyclophosphamide, and low-dose total-body
irradiation followed by unrelated allogeneic umbilical cord blood transplantation and
post-transplant immunosuppression comprising cyclosporine and mycophenolate mofetil.
- Correlate clinical and umbilical cord blood-related factors with engraftment in
patients treated with this regimen.
- Determine transplant-related complications, in terms of toxicity, myelosuppression,
infections, and acute and chronic graft-versus-host disease, in patients treated with
this regimen.
- Determine disease-free and overall survival of patients treated with this regimen.
- Determine treatment-related mortality of patients treated with this regimen.
OUTLINE: This is a uncontrolled, pilot study.
- Nonmyeloablative conditioning regimen: Patients receive fludarabine IV over 30 minutes
daily on days -6 to -2 and cyclophosphamide IV over 2 hours on day -6 and undergo
low-dose total-body irradiation (TBI) on day 0.
- Unrelated allogeneic umbilical cord blood transplantation (UCBT): After completion of
TBI, patients undergo 1 or 2 unrelated allogeneic UCBTs on day 0.
- Post-transplant immunosuppression: Patients receive oral or IV cyclosporine daily
beginning on day -3 and continuing until day 180 and oral or IV mycophenolate mofetil
twice daily on days 0-30.
Patients are followed periodically for 1 year after transplantation.
PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of 1 of the following hematologic malignancies:
- Acute myeloid leukemia (AML) with or without history of myelodysplastic
syndromes, meeting 1 of the following criteria:
- In first complete remission (CR-1) with unfavorable cytogenetics and/or
achieved CR-1 after ≥ 1 course of induction therapy
- Secondary or treatment-related AML
- In second or further complete remission
- Relapsed with ≤ 20% blasts in the bone marrow AND no circulating blasts
- Acute lymphoblastic leukemia (ALL), meeting 1 of the following criteria:
- In CR-1 with unfavorable cytogenetics or elevated WBC at presentation OR
failed to achieve CR-1 after ≥ 4 weeks of induction therapy
- In second or further complete remission
- Relapsed with ≤ 20% blasts in the bone marrow AND no circulating blasts
- Other acute leukemic variants allowed at the discretion of the principal
investigator
- Chronic myelogenous leukemia (CML), meeting 1 of the following criteria:
- In first chronic phase AND refractory to or unable to tolerate imatinib
mesylate
- In second or further chronic phase
- In first or second accelerated phase
- Myelodysplastic syndromes with intermediate 2- or high-risk International
Prognosis Scoring System (IPSS) score, including any of the following:
- Refractory anemia
- Refractory anemia with excess blasts
- Chronic myelomonocytic leukemia
- Myeloproliferative disorders with poor prognosis, including any of the
following:
- Myelofibrosis with myeloid metaplasia
- No ≥ grade 3 myelofibrosis
- Atypical CML
- Juvenile myelomonocytic leukemia
- Other clonal hemopathies with an accepted poor prognosis
- Multiple myeloma with chromosome 13 abnormalities and/or progression after prior
autologous bone marrow transplantation (BMT)
- Chronic lymphocytic leukemia, meeting 1 of the following criteria:
- Primary refractory OR relapsed and refractory disease (less than partial
remission)
- Relapsed twice on or after prior chemotherapy
- Lymphoma, meeting both of the following criteria:
- Hodgkin's or non-Hodgkin's lymphoma in > CR-1 OR failed primary induction
- Chemosensitive disease, defined as > 50% reduction in mass size after the
most recent chemotherapy
- Must meet ≥ 1 of the following criteria:
- Over 45 years of age
- Has undergone prior autologous or allogeneic BMT
- Charlson^ comorbidity score ≥ 2
- Must have a high degree of tumor control (salvage therapy allowed)
- At high risk for treatment-related mortality with a myeloablative conditioning
regimen
- No massive splenomegaly
- Patients may become eligible after splenectomy or radiotherapy to the spleen
- No 5/6 or 6/6 HLA-matched related donor available
- No well-matched (i.e., ≥ 9/10 HLA match by high-resolution typing) unrelated donor
available
PATIENT CHARACTERISTICS:
Performance status
- Not specified
Life expectancy
- Not specified
Hematopoietic
- See Disease Characteristics
Hepatic
- Bilirubin ≤ 2 times upper limit of normal (ULN)
- Transaminases ≤ 4 times ULN (unless due to underlying disease)
Renal
- Creatinine clearance ≥ 50 mL/min
Cardiovascular
- Ejection fraction ≥ 30%
Pulmonary
- DCLO ≥ 35%
Other
- Negative pregnancy test
- No uncontrolled viral, bacterial, or fungal infection
- HIV negative
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
Chemotherapy
- See Disease Characteristics
Radiotherapy
- See Disease Characteristics
Other
- At least 3 months since prior immunosuppressive therapy
- At least 10 days since prior salvage therapy for patients not in at least morphologic
or radiologic complete remission
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Gordon L. Phillips, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
James P. Wilmot Cancer Center
Authority:
Unspecified
Study ID:
CDR0000448637
NCT ID:
NCT00255684
Start Date:
December 2003
Completion Date:
Related Keywords:
- Chronic Myeloproliferative Disorders
- Graft Versus Host Disease
- Leukemia
- Lymphoma
- Multiple Myeloma and Plasma Cell Neoplasm
- Myelodysplastic Syndromes
- Myelodysplastic/Myeloproliferative Neoplasms
- graft versus host disease
- adult acute myeloid leukemia in remission
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities
- 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
- childhood acute myeloid leukemia in remission
- recurrent childhood acute myeloid leukemia
- adult acute lymphoblastic leukemia in remission
- recurrent adult acute lymphoblastic leukemia
- childhood acute lymphoblastic leukemia in remission
- recurrent childhood acute lymphoblastic leukemia
- acute undifferentiated leukemia
- accelerated phase chronic myelogenous leukemia
- chronic phase chronic myelogenous leukemia
- childhood chronic myelogenous leukemia
- refractory anemia with excess blasts
- refractory anemia
- chronic myelomonocytic leukemia
- atypical chronic myeloid leukemia, BCR-ABL1 negative
- juvenile myelomonocytic leukemia
- primary myelofibrosis
- refractory hairy cell leukemia
- stage I multiple myeloma
- stage II multiple myeloma
- stage III multiple myeloma
- refractory multiple myeloma
- refractory chronic lymphocytic leukemia
- stage III adult Hodgkin lymphoma
- stage IV adult Hodgkin lymphoma
- recurrent/refractory childhood Hodgkin lymphoma
- stage III adult Burkitt lymphoma
- stage IV 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 IV adult diffuse large cell lymphoma
- stage IV adult diffuse mixed cell lymphoma
- stage IV adult diffuse small cleaved cell lymphoma
- stage III adult immunoblastic large cell lymphoma
- stage IV adult immunoblastic large cell lymphoma
- stage III adult lymphoblastic lymphoma
- stage IV adult lymphoblastic lymphoma
- stage III grade 1 follicular lymphoma
- stage III grade 2 follicular lymphoma
- stage III grade 3 follicular lymphoma
- stage IV grade 1 follicular lymphoma
- stage IV grade 2 follicular lymphoma
- stage IV grade 3 follicular lymphoma
- stage III mantle cell lymphoma
- stage III marginal zone lymphoma
- stage IV mantle cell lymphoma
- stage IV marginal zone lymphoma
- stage III small lymphocytic lymphoma
- stage IV small lymphocytic lymphoma
- extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
- nodal marginal zone B-cell lymphoma
- splenic marginal zone lymphoma
- adult acute myeloid leukemia with inv(16)(p13;q22)
- adult acute myeloid leukemia with t(15;17)(q22;q12)
- de novo myelodysplastic syndromes
- recurrent mycosis fungoides/Sezary syndrome
- recurrent cutaneous T-cell non-Hodgkin lymphoma
- recurrent childhood large cell lymphoma
- recurrent childhood lymphoblastic lymphoma
- recurrent childhood small noncleaved cell lymphoma
- recurrent adult diffuse large cell lymphoma
- recurrent adult diffuse mixed cell lymphoma
- recurrent adult diffuse small cleaved cell lymphoma
- recurrent grade 1 follicular lymphoma
- recurrent grade 2 follicular lymphoma
- recurrent grade 3 follicular lymphoma
- recurrent marginal zone lymphoma
- recurrent small lymphocytic lymphoma
- recurrent adult Burkitt lymphoma
- recurrent adult immunoblastic large cell lymphoma
- recurrent adult lymphoblastic lymphoma
- recurrent mantle cell lymphoma
- relapsing chronic myelogenous leukemia
- myelodysplastic/myeloproliferative neoplasm, unclassifiable
- previously treated myelodysplastic syndromes
- recurrent adult Hodgkin lymphoma
- secondary acute myeloid leukemia
- secondary myelodysplastic syndromes
- 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
- childhood myelodysplastic syndromes
- Neoplasms
- Graft vs Host Disease
- Leukemia
- Lymphoma
- Lymphoma, Non-Hodgkin
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
- Myelodysplastic Syndromes
- Preleukemia
- Myeloproliferative Disorders
- Lymphoma, Large-Cell, Immunoblastic
- Myelodysplastic-Myeloproliferative Diseases
Name | Location |
|---|---|
| James P. Wilmot Cancer Center at University of Rochester Medical Center | Rochester, New York 14642 |
