Enhancing Anti--Tetanus Vaccine Response After Autologous Stem Cell Transplantation
Study Details
Study Description
Brief Summary
This pilot randomized Phase II trial (10 subjects per arm) will compare immune reconstitution following transplantation of an autologous mobilized graft product to reconstitution following transplantation of a mobilized graft product followed by an autologous lymphocyte infusion collected prior to G-CSF mobilization. All subjects will receive tetanus vaccines pre and post-transplant. The primary end point will be tetanus vaccine immune responses post-transplant.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
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To compare the cellular and humoral vaccine response post-transplant between the two arms by performing Elisa, and T-cell enzyme-linked immunospot (ELISPOT) assays
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To determine the feasibility and safety of this approach
SECONDARY OBJECTIVES:
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To compare post-transplant recovery of innate and adaptive immune cells (CD8, CD4, CD19, NK, γδ T-cells), in addition to T-cell phenotype markers between the two arms.
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To compare post-transplant recovery of T-regs and MDSCs between the two arms.
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To compare progression free survival (PFS) at 2 years post-transplant
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm I (vaccine, CD34 transplant, DLI) ARM I: Patients receive 3 doses of tetanus before transplant and on days 15, and 60 post transplant. |
Drug: Melphalan
Given IV
Other Names:
Procedure: Peripheral Blood Stem Cell Transplantation--CD34 HSCT
Undergo autologous CD34 HSCT
Other Names:
Procedure: Peripheral Blood Stem Cell Transplantation--AHSCT
Undergo AHSCT
Other Names:
Biological: T Cell-Depleted Hematopoietic Stem Cell Transplantation
Undergo autologous CD34 HSCT
Biological: Tetanus Toxoid Vaccine
Given IM
Other Names:
|
| Active Comparator: Arm II (vaccine, stem cell transplant) Patients receive 3 doses of tetanus as in Arm I. Patients receive high-dose melphalan IV on day -2 and undergo AHSCT on day 0. |
Drug: Melphalan
Given IV
Other Names:
Procedure: Peripheral Blood Stem Cell Transplantation--AHSCT
Undergo AHSCT
Other Names:
Biological: Tetanus Toxoid Vaccine
Given IM
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of safely treated patients (feasibility and safety) [Baseline to 180 days post-transplant]
Determine safety of outcomes by CTCAE version 5.0 tool
Secondary Outcome Measures
- Progression-free survival [Up to 2 years post-transplant]
Kaplan Meier method, Logrank test, and Cox model will be employed to investigate the effect of ALC, AMC, and immune cells on survival post AHSCT.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age ≥ 19 years to 70 years old at time of study entry (consent)
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Diagnosis of Multiple Myeloma as per updated International Myeloma Working Group (IMWG) criteria .
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Must have measurable disease defined as: for secretory MM, serum monoclonal protein ≥1.0 g/dL, urine monoclonal protein ≥200 mg/24 hrs, and involved free light chain ≥ 10 mg/dL; or in case of non-secretory MM, bone marrow plasma cell percentage ≥30%.
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Must have standard risk myeloma (see exclusion criterion 4).
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Must have received bortezomib, lenalidomide and dexamethasone (VRd) as a form of induction therapy pre-AHSCT (use of cyclophosphamide, bortezomib and dexamethasone may be allowed for up to 2 weekly doses before initiation of VRd induction, if necessary clinically for cytoreduction)
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Able to understand and sign a consent form.
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Creatinine clearance equal or > 60 ml/min (calculated)
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Ejection fraction equal or > 50% before admission for transplant as per institutional standards. Patients with coronary heart disease (recent myocardial infarctions, angina, cardiac stent, or bypass surgery in the last 6 months or arrhythmia) need to be cleared by cardiology as per institutional BMT standards.
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Serum bilirubin, ALT, AST less than 3 X upper limit of normal
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FVC, FEV1 or DLCO >50% predicted before admission for transplant as per institutional standards. Patients on home oxygen are not allowed on the protocol.
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No more than 6 months of pre-transplant MM chemotherapy is allowed (from the date of the start of the induction therapy).
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KPS ≥ 70%or ECOG 0-2.
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Must be eligible to receive Melphalan dose of 200mg/m2
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A female of child-bearing potential, must have two negative urine pregnancy test results within 10 to 14 days prior to starting the first dose of vaccine pre-transplant as a way of ensuring safe transplant planning.
Exclusion Criteria:
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Participation in another clinical study with an investigational product during the last 28 days.
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Prior stem cell transplant (either autologous or allogeneic)
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Creatinine clearance < 60 ml/min (calculated)
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High risk MM defined as those with the following disease, fluorescence in situ hybridization and/or cytogenetic features: del17p, del1p with 1q gain, t(4;14), t(14;16), t(14;20), >1 cytogenetic abnormality on karyotype, hypodiploid, plasma cell leukemia (primary or secondary), or subjects who failed to achieve ≥PR to induction therapy (i.e. VRd) and required salvage induction prior to AHSCT.
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Documented central nervous system or extramedullary disease.
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Significant organ dysfunction deemed to carry inappropriate risk for AHSCT.
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Intention or plans for cyclophosphamide mobilization.
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Known allergic reactions after previous tetanus diphtheria vaccination or had a condition of Guillain Barre Syndrome (GBS)
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Known active hepatitis B, C or HIV infections on initial assessment.
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Enrollment on any other transplant related protocols.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Nebraska Medical Center | Omaha | Nebraska | United States | 68198 |
Sponsors and Collaborators
- University of Nebraska
Investigators
- Principal Investigator: Muhamed Baljevic, MD, University of Nebraska
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 669-19
- NCI-2015-00743