Phase I/II Clinical Trial Combining hTERT Tumor Vaccine & Autologous T Cells in Patients With Advanced Myeloma

Phase 1

Completed

• Conditions: Multiple Myeloma
• Interventions: Biological: hTERT vaccine, GM-CSF, PCV, T cell infusion; Biological: GM-CSF, PCV, T cell infusion

• Registration Number: NCT00834665
• Lead Sponsor: University of Pennsylvania

Brief Summary

The purpose of this study is:

1. To evaluate the safety of activated T cell infusions and immunization with hTERT multi-peptide vaccine in the post-transplant setting and whether the combination can delay hematopoietic recovery or induce other autoimmune events.

2. To determine whether the strategy of infusing vaccine-primed T-cells early after transplant in conjunction with post-transplant boosters leads to the induction of cellular immune responses to hTERT.

Detailed Description

This protocol proposes to combine two different investigational products to test the hypothesis that autologous T cell therapy can augment the potency of a putative tumor vaccine post- stem cell transplant, and lead to a myeloma-directed T-cell mediated "graft vs. myeloma" effect in patients with advance myeloma. The hope is that this combination therapy approach will result in a more rapid recovery of acquired immunity and consequently increased cure rates and better clinical outcomes. The two investigational products to be evaluated in this Phase I/II study include:

1. hTERT Vaccine (the putative tumor vaccine)- a multi-peptide vaccine consisting of 3 peptides against the catalytic subunit of telomerase (hTERT D988Y, I540, and R572Y), 1 survivin peptide (Sur1M2- an antiapoptotic protein), and 1 CMV (cytopeptide (N495).

2. T cell therapy- T-cells isolated from the patient and activated/expanded ex vivo by antiCD3/28 beads.

This is a two-site study at the University of Pennsylvania and University of Maryland to recruit a total of fifty-six study patients. The key eligibility criteria are patients who have systemic or multifocal myeloma requiring autologous stem cell transplantation. After enrollment, patients will be divided into two arms (A and B) according to their HLA A2 status (A = HLA A2 +, B = HLA A2-). Patients in ARM A will be initially immunized with the hTERT vaccine along with a pneumococcal conjugate vaccine (PCV); patients in ARM B will be initially immunized and given boosters of PCV only. All patients will undergo T-cell harvest, stem cell mobilization and collection, high-dose chemotherapy, autologous stem cell transplant (ASCT), and an infusion of expanded T cells at day 2 after ASCT. Patients in ARM A will then receive three hTERT/PCV vaccine boosters at day 14, 42, and 90 after ASCT.

Study Timeline

• Study Start: 2006-12
• Study First Submitted: 2008-01-03
• Study First Submitted QC: 2009-02-02
• Study First Posted: 2009-02-03
• Primary Completion: 2017-12
• Study Completion: 2017-12
• Status Verified: 2019-10
• Last Update Submitted: 2019-10-21
• Last Update Posted: 2019-10-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 59

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
hTERT/GM-CSF+PCV, T cell infusion	hTERT vaccine, GM-CSF, PCV, T cell infusion	ARM A = hTERT/GM-CSF+PCV, T cell infusion
GM-CSF+PCV, T cell infusion,GM-CSF+PVC	GM-CSF, PCV, T cell infusion	ARM B GM-CSF+PCV, T cell infusion,GM-CSF+PVC

Primary Outcome Measures

Name	Time	Method
Primary toxicity endpoint	2 yrs	Incidence of delayed hematopoietic recovery and the incidence of Grade 3 or greater autoimmune events

Trial Locations

Locations (2)

Greenbaum Cancer Center; 🇺🇸 Baltimore, Maryland, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States