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

NCT ID: NCT02700841

Last Updated: 2024-03-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-09
• Study Completion Date: 2022-12-21

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

Conditions

Plasma Cell Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I (vaccine, CD34 transplant, DLI)

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

Group Type: EXPERIMENTAL

Melphalan

Intervention Type: DRUG

Given IV

Peripheral Blood Stem Cell Transplantation--CD34 HSCT

Intervention Type: PROCEDURE

Undergo autologous CD34 HSCT

Peripheral Blood Stem Cell Transplantation--AHSCT

Intervention Type: PROCEDURE

Undergo AHSCT

T Cell-Depleted Hematopoietic Stem Cell Transplantation

Intervention Type: BIOLOGICAL

Undergo autologous CD34 HSCT

Tetanus Toxoid Vaccine

Intervention Type: BIOLOGICAL

Given IM

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.

Group Type: ACTIVE_COMPARATOR

Melphalan

Intervention Type: DRUG

Given IV

Peripheral Blood Stem Cell Transplantation--AHSCT

Intervention Type: PROCEDURE

Undergo AHSCT

Tetanus Toxoid Vaccine

Intervention Type: BIOLOGICAL

Given IM

Interventions

Melphalan

Given IV

Intervention Type: DRUG

Peripheral Blood Stem Cell Transplantation--CD34 HSCT

Undergo autologous CD34 HSCT

Intervention Type: PROCEDURE

Peripheral Blood Stem Cell Transplantation--AHSCT

Undergo AHSCT

Intervention Type: PROCEDURE

T Cell-Depleted Hematopoietic Stem Cell Transplantation

Undergo autologous CD34 HSCT

Intervention Type: BIOLOGICAL

Tetanus Toxoid Vaccine

Given IM

Intervention Type: BIOLOGICAL

Other Intervention Names

Alkeran; L-PAM; L-Phenylalanine Mustard; Phenylalanine Mustard; Sarcolysin; PBPC Transplantation; Peripheral Blood Progenitor Cell Transplantation; Peripheral Stem Cell Support; Peripheral Stem Cell Transplantation; PBPC transplantation; Peripheral Blood Progenitor Cell Transplantation; Peripheral Stem Cell Support; Peripheral Stem Cell Transplantation; Tetanus Toxoid; TT

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Nebraska

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christopher D'Angelo, MD

Role: PRINCIPAL_INVESTIGATOR

University of Nebraska

Locations

University of Nebraska Medical Center

Omaha, Nebraska, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2015-00743

Identifier Type: REGISTRY

Identifier Source: secondary_id

0669-19-FB

Identifier Type: -

Identifier Source: org_study_id