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

Phase 2

Terminated

Conditions: Plasma Cell Myeloma

Interventions: 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

Registration Number: NCT02700841

Lead Sponsor: University of Nebraska

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.

Detailed Description: PRIMARY OBJECTIVES:

1. 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

2. To determine the feasibility and safety of this approach

SECONDARY OBJECTIVES:

1. 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.

2. To compare post-transplant recovery of T-regs and MDSCs between the two arms.

3. To compare progression free survival (PFS) at 2 years post-transplant

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 8

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (vaccine, CD34 transplant, DLI)	T Cell-Depleted Hematopoietic Stem Cell Transplantation	ARM I: Patients receive 3 doses of tetanus before transplant and on days 15, and 60 post transplant.
Arm I (vaccine, CD34 transplant, DLI)	Tetanus Toxoid Vaccine	ARM I: Patients receive 3 doses of tetanus before transplant and on days 15, and 60 post transplant.
Arm I (vaccine, CD34 transplant, DLI)	Peripheral Blood Stem Cell Transplantation--CD34 HSCT	ARM I: Patients receive 3 doses of tetanus before transplant and on days 15, and 60 post transplant.
Arm I (vaccine, CD34 transplant, DLI)	Peripheral Blood Stem Cell Transplantation--AHSCT	ARM I: Patients receive 3 doses of tetanus before transplant and on days 15, and 60 post transplant.
Arm II (vaccine, stem cell transplant)	Peripheral Blood Stem Cell Transplantation--AHSCT	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.
Arm II (vaccine, stem cell transplant)	Tetanus Toxoid Vaccine	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.
Arm I (vaccine, CD34 transplant, DLI)	Melphalan	ARM I: Patients receive 3 doses of tetanus before transplant and on days 15, and 60 post transplant.
Arm II (vaccine, stem cell transplant)	Melphalan	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.

Primary Outcome Measures

Name	Time	Method
Number of Safely Treated Participants (Feasibility and Safety)	Through 180 days post-transplant	Determine safety of outcomes based on the number of safely treated participants by CTCAE version 5.0 tool

Secondary Outcome Measures