- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02181478
Intra-Osseous Co-Transplant of UCB and hMSC
Intra-osseous Co-transplant of Cord Blood and Mesenchymal Stromal Cells: A Feasibility Study
Study Overview
Status
Conditions
- Myelodysplastic Syndromes
- Hodgkin Lymphoma
- Refractory Hodgkin Lymphoma
- Myelofibrosis
- Acute Lymphoblastic Leukemia
- Acute Myelogenous Leukemia
- Chronic Myelogenous Leukemia
- Refractory Chronic Lymphocytic Leukemia
- Refractory Non-Hodgkin Lymphoma
- Lymphoid Malignancies
- Relapsed Non-Hodgkin Lymphoma
- Relapsed Chronic Lymphocytic Leukemia
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
-
-
Ohio
-
Cleveland, Ohio, United States, 44106-5065
- Case Comprehensive Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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. |
All patients will receive a single IV dose of 50 mg/kg of cyclophosphamide on day -6
Other Names:
Given by IV during prep at 40mg/m2 for 5 days
Other Names:
Undergo single fraction of reduced intensity conditioning (RIC) regimen of 200 cGy TBI without shielding on day -1
Other Names:
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
Other Names:
Given at 1g intravenously or orally twice daily from day -5 to +100, or as clinically indicated.
Other Names:
Following RIC, on day T+0, dimethylsulphoxide will be removed from the cord blood cells and given as transplant.
Other Names:
The total dosage of hMSC will be 2x10^6cells/kg (+/-20%).
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of patients with BM cellularity failure: Measure of feasibility
Time Frame: 42 days after transplant
|
Primary graft failure is defined by <10% BM cellularity in bone marrow biopsies.
Failure in more than 30% of patients will indicate unfeasibility of treatment
|
42 days after transplant
|
Number of patients with ANC failure without evidence of disease: Measure of feasibility
Time Frame: 42 days after transplant
|
Primary graft failure is defined by <500 ANC cell/ul in bone marrow biopsies.
Failure in more than 30% of patients will indicate unfeasibility of treatment
|
42 days after transplant
|
Number of patients with hematopoietic recovery without evidence of donor umbilical cord blood engraftment: Measure of feasibility
Time Frame: 42 days after transplant
|
Primary graft failure is defined by hematopoietic recovery with <10% donor cell chimerism.
Failure in more than 30% of patients will indicate unfeasibility of treatment
|
42 days after transplant
|
Number of patients with hematopoietic recovery without evidence of donor umbilical cord blood engraftment: Measure of feasibility
Time Frame: 100 days after transplant
|
Primary graft failure is defined by hematopoietic recovery with <40% donor cell chimerism.
Failure in more than 30% of patients will indicate unfeasibility of treatment
|
100 days after transplant
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of toxicities assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time Frame: Up to 12 months
|
Descriptive statistics will be used.
|
Up to 12 months
|
Rate of neutrophil recovery
Time Frame: Up to 12 months
|
The rate of neutrophil recovery and median time of recovery will be estimated using the methods of Kaplan and Meier.
|
Up to 12 months
|
Rate of platelet recovery
Time Frame: Up to 12 months
|
The rate of platelet recovery and median time of recovery will be estimated using the methods of Kaplan and Meier.
|
Up to 12 months
|
Median time of neutrophil recovery
Time Frame: Up to 12 months
|
The median time of neutrophil recovery will be estimated using the methods of Kaplan and Meier.
|
Up to 12 months
|
Median time of platelet recovery
Time Frame: Up to 12 months
|
The median time of platelet recovery will be estimated using the methods of Kaplan and Meier.
|
Up to 12 months
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Bone Marrow Diseases
- Hematologic Diseases
- Myeloproliferative Disorders
- Leukemia, B-Cell
- Lymphoma
- Myelodysplastic Syndromes
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Hodgkin Disease
- Lymphoma, Non-Hodgkin
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Dermatologic Agents
- Anti-Bacterial Agents
- Antibiotics, Antineoplastic
- Antifungal Agents
- Antitubercular Agents
- Antibiotics, Antitubercular
- Calcineurin Inhibitors
- Cyclophosphamide
- Fludarabine
- Fludarabine phosphate
- Mycophenolic Acid
- Cyclosporine
- Cyclosporins
Other Study ID Numbers
- CASE1Z14 (Other Identifier: Case Comprehensive Cancer Center)
- P30CA043703 (U.S. NIH Grant/Contract)
- NCI-2014-01316 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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