This clinical trial studies intra-osseous donor umbilical cord blood and mesenchymal stromal
cell co-transplant in treating patients with hematologic malignancies. Giving low doses of
chemotherapy and total-body irradiation before a co-transplant of donor umbilical cord blood
and mesenchymal stromal cells into the bone (intra-osseous) helps stop the growth of cancer
cells. It may also stop the patient's immune system from rejecting the donor's stem cells.
The donated stem cells may replace the patient's immune cells and help destroy any remaining
cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can
also make an immune response against the body's normal cells. Giving cyclosporine and
mycophenolate mofetil at the time of transplant may stop this from happening.
PRIMARY OBJECTIVES:
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.
Inclusion Criteria:
- Patients must have one of the following malignancies:
- 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:
- Patients with inadequate Organ Function as defined by:
- 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
