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

NCT02700841 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 0669-19-FBNCI-2015-00743
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

Arm I (vaccine, CD34 transplant, DLI)

EXPERIMENTAL

ARM I: Patients receive 3 doses of tetanus before transplant and on days 15, and 60 post transplant.

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

Arm II (vaccine, stem cell transplant)

ACTIVE COMPARATOR

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; Procedure: Peripheral Blood Stem Cell Transplantation--AHSCT; Biological: Tetanus Toxoid Vaccine

Interventions

Melphalan DRUG

Given IV

Also known as: Alkeran, L-PAM, L-Phenylalanine Mustard, Phenylalanine Mustard, Sarcolysin

Arm I (vaccine, CD34 transplant, DLI); Arm II (vaccine, stem cell transplant)

Peripheral Blood Stem Cell Transplantation--CD34 HSCT PROCEDURE

Undergo autologous CD34 HSCT

Also known as: PBPC Transplantation, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplantation

Arm I (vaccine, CD34 transplant, DLI)

Peripheral Blood Stem Cell Transplantation--AHSCT PROCEDURE

Undergo AHSCT

Also known as: PBPC transplantation, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplantation

Arm I (vaccine, CD34 transplant, DLI); Arm II (vaccine, stem cell transplant)

T Cell-Depleted Hematopoietic Stem Cell Transplantation BIOLOGICAL

Undergo autologous CD34 HSCT

Arm I (vaccine, CD34 transplant, DLI)

Tetanus Toxoid Vaccine BIOLOGICAL

Given IM

Also known as: Tetanus Toxoid, TT

Arm I (vaccine, CD34 transplant, DLI); Arm II (vaccine, stem cell transplant)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Nebraska: lead

Study Sites (1)

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Melphalan; Peripheral Blood Stem Cell Transplantation; Tetanus Toxoid

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Toxoids; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: IIT Office
• Organization: University of Nebraska Medical Center

IITOffice@unmc.edu

402-559-4596

Study Officials

• Christopher D'Angelo, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2016
• First Posted: March 7, 2016
• Study Start: January 9, 2020
• Primary Completion: December 21, 2022
• Study Completion: December 21, 2022
• Last Updated: March 12, 2024
• Results First Posted: March 12, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)