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

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

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.

Study Overview

• Status: Terminated
• Conditions: Plasma Cell Myeloma
• Intervention / Treatment: 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

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

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 19 years to 70 years old at time of study entry (consent)
2. Diagnosis of Multiple Myeloma as per updated International Myeloma Working Group (IMWG) criteria .
3. 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%.
4. Must have standard risk myeloma (see exclusion criterion 4).
5. 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)
6. Able to understand and sign a consent form.
7. Creatinine clearance equal or > 60 ml/min (calculated)
8. 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.
9. Serum bilirubin, ALT, AST less than 3 X upper limit of normal
10. FVC, FEV1 or DLCO >50% predicted before admission for transplant as per institutional standards. Patients on home oxygen are not allowed on the protocol.
11. No more than 6 months of pre-transplant MM chemotherapy is allowed (from the date of the start of the induction therapy).
12. KPS ≥ 70%or ECOG 0-2.
13. Must be eligible to receive Melphalan dose of 200mg/m2
14. 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:

1. Participation in another clinical study with an investigational product during the last 28 days.
2. Prior stem cell transplant (either autologous or allogeneic)
3. Creatinine clearance < 60 ml/min (calculated)
4. 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.
5. Documented central nervous system or extramedullary disease.
6. Significant organ dysfunction deemed to carry inappropriate risk for AHSCT.
7. Intention or plans for cyclophosphamide mobilization.
8. Known allergic reactions after previous tetanus diphtheria vaccination or had a condition of Guillain Barre Syndrome (GBS)
9. Known active hepatitis B, C or HIV infections on initial assessment.
10. Enrollment on any other transplant related protocols.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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: Alkeran; L-PAM; L-Phenylalanine Mustard; Phenylalanine Mustard; Sarcolysin; Procedure: Peripheral Blood Stem Cell Transplantation--CD34 HSCT; Undergo autologous CD34 HSCT; Other Names: Peripheral Blood Progenitor Cell Transplantation; Peripheral Stem Cell Support; Peripheral Stem Cell Transplantation; PBPC Transplantation; Procedure: Peripheral Blood Stem Cell Transplantation--AHSCT; Undergo AHSCT; Other Names: PBPC transplantation; Peripheral Blood Progenitor Cell Transplantation; Peripheral Stem Cell Support; Peripheral Stem Cell Transplantation; Biological: T Cell-Depleted Hematopoietic Stem Cell Transplantation; Undergo autologous CD34 HSCT; Biological: Tetanus Toxoid Vaccine; Given IM; Other Names: TT; Tetanus Toxoid
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: Alkeran; L-PAM; L-Phenylalanine Mustard; Phenylalanine Mustard; Sarcolysin; Procedure: Peripheral Blood Stem Cell Transplantation--AHSCT; Undergo AHSCT; Other Names: PBPC transplantation; Peripheral Blood Progenitor Cell Transplantation; Peripheral Stem Cell Support; Peripheral Stem Cell Transplantation; Biological: Tetanus Toxoid Vaccine; Given IM; Other Names: TT; Tetanus Toxoid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Safely Treated Participants (Feasibility and Safety)	Determine safety of outcomes based on the number of safely treated participants by CTCAE version 5.0 tool	Through 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

Collaborators and Investigators

• Sponsor: University of Nebraska
• Investigators: Principal Investigator: Christopher D'Angelo, MD, University of Nebraska

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2020
• Primary Completion (Actual): December 21, 2022
• Study Completion (Actual): December 21, 2022

Study Registration Dates

• First Submitted: March 2, 2016
• First Submitted That Met QC Criteria: March 2, 2016
• First Posted (Estimated): March 7, 2016

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Infections; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Clostridium Infections; Multiple Myeloma; Neoplasms, Plasma Cell; Tetanus; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Melphalan; Mechlorethamine
• Other Study ID Numbers: 0669-19-FB; NCI-2015-00743 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No