Enhancing Anti--Tetanus Vaccine Response After Autologous Stem Cell Transplantation

Study Overview
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Brief Summary
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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.

Detailed Description
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PRIMARY OBJECTIVES: 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 To determine the feasibility and safety of this approach SECONDARY OBJECTIVES: 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. To compare post-transplant recovery of T-regs and MDSCs between the two arms. To compare progression free survival (PFS) at 2 years post-transplant

Official Title
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A Phase II Study of Enhancing Anti-Tetanus Vaccine Response After Autologous Stem Cell Transplantation

Conditions
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Plasma Cell Myeloma

Intervention / Treatment
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* Drug: Melphalan
* Procedure: Peripheral Blood Stem Cell Transplantation--CD34 HSCT
* Procedure: Peripheral Blood Stem Cell Transplantation--AHSCT
* Biological: T Cell-Depleted Hematopoietic Stem Cell Transplantation
* Biological: Tetanus Toxoid Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 19 years to 70 years old at time of study entry (consent) Diagnosis of Multiple Myeloma as per updated International Myeloma Working Group (IMWG) criteria . 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%. Must have standard risk myeloma (see exclusion criterion 4). 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) Able to understand and sign a consent form. Creatinine clearance equal or > 60 ml/min (calculated) 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. Serum bilirubin, ALT, AST less than 3 X upper limit of normal FVC, FEV1 or DLCO >50% predicted before admission for transplant as per institutional standards. Patients on home oxygen are not allowed on the protocol. No more than 6 months of pre-transplant MM chemotherapy is allowed (from the date of the start of the induction therapy). KPS ≥ 70%or ECOG 0-2. Must be eligible to receive Melphalan dose of 200mg/m2 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: Participation in another clinical study with an investigational product during the last 28 days. Prior stem cell transplant (either autologous or allogeneic) Creatinine clearance < 60 ml/min (calculated) 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. Documented central nervous system or extramedullary disease. Significant organ dysfunction deemed to carry inappropriate risk for AHSCT. Intention or plans for cyclophosphamide mobilization. Known allergic reactions after previous tetanus diphtheria vaccination or had a condition of Guillain Barre Syndrome (GBS) Known active hepatitis B, C or HIV infections on initial assessment. Enrollment on any other transplant related protocols.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (vaccine, CD34 transplant, DLI)<br>ARM I: Patients receive 3 doses of tetanus before transplant and on days 15, and 60 post transplant. | Drug: Melphalan<br>* Given IV<br>* Other names: Sarcolysin;Procedure: Peripheral Blood Stem Cell Transplantation--CD34 HSCT<br>* Undergo autologous CD34 HSCT<br>* Other names: Peripheral Stem Cell Transplantation;Procedure: Peripheral Blood Stem Cell Transplantation--AHSCT<br>* Undergo AHSCT<br>* Other names: Peripheral Stem Cell Transplantation;Biological: T Cell-Depleted Hematopoietic Stem Cell Transplantation<br>* Undergo autologous CD34 HSCT<br>Biological: Tetanus Toxoid Vaccine<br>* Given IM<br>* Other names: TT;|
| Active Comparator: Arm II (vaccine, stem cell transplant)<br>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<br>* Given IV<br>* Other names: Sarcolysin;Procedure: Peripheral Blood Stem Cell Transplantation--AHSCT<br>* Undergo AHSCT<br>* Other names: Peripheral Stem Cell Transplantation;Biological: Tetanus Toxoid Vaccine<br>* Given IM<br>* Other names: TT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of safely treated patients (feasibility and safety) | Determine safety of outcomes by CTCAE version 5.0 tool | Baseline to 180 days post-transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | 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. | Up to 2 years post-transplant |