Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
EARLY_PHASE1
6 participants
INTERVENTIONAL
2015-07-22
2020-02-07
Brief Summary
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Detailed Description
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I. To estimate the feasibility of combining intra-osseous umbilical cord blood (UCB) hematopoietic stem cells and human mesenchymal stromal cells (hMSC) following reduced intensity conditioning (RIC).
SECONDARY OBJECTIVES:
I. To estimate the time to engraftment of intra-osseous (IO) UCB transplant combined with hMSC following RIC.
II. To estimate the safety profile of IO UBC transplant combined with hMSC.
OUTLINE:
REDUCED INTENSITY CONDITIONING: Patients receive cyclophosphamide intravenously (IV) over 2 hours on day -6 and fludarabine phosphate IV on days -6 to -2 and undergo total body irradiation (TBI) on day -1.
GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive cyclosporine orally (PO) or IV over 2 hours every 12 hours on beginning on days -5 to 100 with taper beginning on day 100 and mycophenolate mofetil IV or PO twice daily (BID) on days -5 to 100.
TRANSPLANT: Patients undergo intra-osseous UCB and hMSC co-transplant on day 0.
After completion of study treatment, patients are followed up at days 28 and 100, and then at 6, 9, and 12 months.
Conditions
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Keywords
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Treatment (intra-osseous UCB with hMSC co-transplant)
REDUCED INTENSITY CONDITIONING (RIC):
Flu/Cy/TBI: Patients receive cyclophosphamide IV over 2 hours on day -6 and fludarabine phosphate IV on days -6 to -2 and undergo total-body irradiation on day -1.
Flu/Mel: Patients receive fludarabine daily on days -5 to -2, a single dose of melphalan on day -2, and ATG on day -3 and day-2.
GVHD PROPHYLAXIS: Patients receive cyclosporine PO or IV over 2 hours every 12 hours on beginning on days -5 to 100 with taper beginning on day 100 and mycophenolate mofetil IV or PO BID on days -5 to 100.
TRANSPLANT: Patients undergo a co-transplantation of an intra-osseous umbilical cord blood transplantation and a mesenchymal stem cell transplantation on day 0.
cyclophosphamide
All patients will receive a single IV dose of 50 mg/kg of cyclophosphamide on day -6
fludarabine phosphate
Given by IV during prep at 40mg/m2 for 5 days
total-body irradiation
Undergo single fraction of reduced intensity conditioning (RIC) regimen of 200 cGy TBI without shielding on day -1
cyclosporine
Initiated in patients on the day -5. Cyclosporine will be administered orally or intravenously at 2 mg/kg/dose every 12 hours for 2-hour period. Cyclosporine will continue until day +100
mycophenolate mofetil
Given at 1g intravenously or orally twice daily from day -5 to +100, or as clinically indicated.
umbilical cord blood transplantation
Following RIC, on day T+0, dimethylsulphoxide will be removed from the cord blood cells and given as transplant.
mesenchymal stem cell transplantation
The total dosage of hMSC will be 2x10\^6cells/kg (+/-20%).
Interventions
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cyclophosphamide
All patients will receive a single IV dose of 50 mg/kg of cyclophosphamide on day -6
fludarabine phosphate
Given by IV during prep at 40mg/m2 for 5 days
total-body irradiation
Undergo single fraction of reduced intensity conditioning (RIC) regimen of 200 cGy TBI without shielding on day -1
cyclosporine
Initiated in patients on the day -5. Cyclosporine will be administered orally or intravenously at 2 mg/kg/dose every 12 hours for 2-hour period. Cyclosporine will continue until day +100
mycophenolate mofetil
Given at 1g intravenously or orally twice daily from day -5 to +100, or as clinically indicated.
umbilical cord blood transplantation
Following RIC, on day T+0, dimethylsulphoxide will be removed from the cord blood cells and given as transplant.
mesenchymal stem cell transplantation
The total dosage of hMSC will be 2x10\^6cells/kg (+/-20%).
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Acute myelogenous leukemia (AML): high-risk AML including:
* Antecedent hematological disease (e.g., myelodysplasia \[MDS\])
* Treatment-related leukemia
* Complete remission (first complete remission \[CR1\]) with poor-risk cytogenetics or molecular markers (e.g. fms-related tyrosine kinase 3 \[Flt 3\] mutation, 11q23, del 5, del 7, complex cytogenetics)
* Second complete remission (CR2) or third complete remission (CR3)
* Induction failure or first relapse with either
* ≤ 10% blasts in the marrow and/or
* ≤ 5% blasts in the peripheral blood
* Acute lymphoblastic leukemia (ALL)
* High-risk CR1 including:
* Poor-risk cytogenetics (e.g., Philadelphia chromosome t(9;22)or 11q23 rearrangements)
* Presence of minimal disease by flow cytometry after 2 or more cycles of chemotherapy
* No complete remission (CR) within 4 weeks of initial treatment
* Induction failure
* CR2 or CR3 with either:
* ≤ 10% blasts in the marrow and/or
* ≤ 5% blasts in the peripheral blood
* Myelodysplastic syndromes (MDS), Intermediate-1 (INT-1), intermediate-2 (INT-2) or high Revised International Prognostic Scoring System (IPSS-R) score that has failed at least 1 first line therapy
* Myelofibrosis (MF):
* Intermediate-2 or high risk by Dynamic International Prognostic Scoring System (DIPSS)-plus
* Monosomal karyotype
* Presence of inv(3)/i(17q) abnormalities
* Other unfavorable karyotype OR leukocytes ≥40 X 10\^9/L AND
* Circulating blasts ≤ 9%
* Relapsed or refractory lymphoid malignancies (including non-Hodgkin lymphoma, Hodgkin lymphoma and chronic lymphocytic leukemia) meeting the following criteria:
* Disease status: stable disease, partial remission or 2nd and 3rd complete remission
* Chronic myelogenous leukemia (CML) in second chronic phase after accelerated or blast crisis; blast crisis defined as:
* Blast count ≥ 20% in the peripheral blood or bone marrow
* Large foci of blasts on bone marrow
* Presence of extra-medullary blastic infiltrate (myeloid sarcoma or chloroma)
* Recipients of prior autologous or allogeneic transplant are eligible, as long as at least 3 months have passed since the transplant, and the patient fulfills other eligibility criteria
* Eastern Cooperative Oncology Group (ECOG) performance status ≤2
* Candidates for reduced intensity conditioning regimens
* Patients who do not have HLA-matched (defined as matched in HLA A, B, C, and DRB1) related or unrelated donors, those who elect to undergo UCB even if they have a MRD or MUD, or patients who require a UCB either for emergency indications such as primary graft failure.
* Cord Blood Units available through NMDP with the following minimal criteria:
* HLA Match: 4/6 or better match (HLA A, B, DRB1)
* Cell dose: Minimum of 2.0x107TNC/kg pre thaw
* Concurrent therapy for extramedullary leukemia or central nervous system (CNS) lymphoma: concurrent therapy or prophylaxis for testicular leukemia, CNS leukemia, and CNS lymphoma including standard intrathecal chemotherapy and/or radiation therapy will be allowed as clinically indicated; such treatment may continue until the planned course is completed; subjects must be in CNS remission at the time of protocol enrollment if there is a history of CNS involvement
* Subjects must have a back-up umbilical cord on the registry in addition to the umbilical cord being used in this study
* Subjects must have the ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria
* Creatinine clearance \< 30 ml/min
* Bilirubin ≥ 2 x institutional upper limit of normal
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) ≥ 2 x institutional upper limit of normal
* Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) ≥ 2 x institutional upper limit of normal
* Corrected diffusing capacity of the lung for carbon monoxide (DLCOcorr) \< 40% normal
* Left ventricular ejection fraction \< 35%
* Patients with uncontrolled inter-current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant or breastfeeding women are excluded from this study
18 Years
75 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Case Comprehensive Cancer Center
OTHER
Responsible Party
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Marcos de Lima
Principal Investigator
Principal Investigators
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Leland Metheny, MD
Role: PRINCIPAL_INVESTIGATOR
Case Comprehensive Cancer Center
Locations
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Case Comprehensive Cancer Center
Cleveland, Ohio, United States
Countries
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Other Identifiers
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NCI-2014-01316
Identifier Type: REGISTRY
Identifier Source: secondary_id
CASE1Z14
Identifier Type: OTHER
Identifier Source: secondary_id
CASE1Z14
Identifier Type: -
Identifier Source: org_study_id