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

Phase I/II Combination Immunotherapy After ASCT for Advanced Myeloma to Study HTERT Vaccination Followed by Adoptive Transfer of Vaccine-Primed Autologous T Cells

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Biological: hTERT vaccine, GM-CSF, PCV, T cell infusion; Biological: GM-CSF, PCV, T cell infusion

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 Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Greenbaum Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Each subject must meet ALL of the following criteria during screening to be enrolled in the study:

1. Written informed consent must be obtained from all patients before entry into the study
2. Patients must have a diagnosis of myeloma

3. Patients must meet one of the following criteria:

   • Myeloma has relapsed, progressed, or failed to respond after at least one prior course of therapy.
   • Myeloma has responded partially to initial therapy but neither a complete nor a near-complete response has developed after at least 3 cycles or months of initial therapy.
   • Myeloma has high-risk features
4. Patients must have measurable disease on study entry.
5. Patients must be between ages 18-80 (inclusive).
6. Patients should have adequate vital organ function.
7. ECOG performance status 0-2
8. Women of child-bearing potential (WOCBP) and their spouses or partners must be willing to use adequate contraception for the duration of the active treatment phase of the study and for at least 4 months after the last dose of chemotherapy. In addition, contraceptive measures must be continued as long as the patient remains on maintenance thalidomide in accordance with the STEPS program.

Key Exclusion Criteria

Subjects who meet ANY of the following criteria cannot be enrolled in the study:

1. Pregnant or nursing females
2. HIV, HTLV-1/2 seropositivity
3. Known history of myelodysplasia
4. Known history of chronic active hepatitis or liver cirrhosis (if suspected by laboratory studies, should be confirmed by liver biopsy).
5. Active Hepatitis B
6. Prior autotransplant or allogeneic transplant
7. More than 4 distinct, prior courses of therapy for myeloma
8. History of severe autoimmune disease requiring steroids or other immunosuppressive treatments.
9. Active immune-mediated diseases including: connective tissue diseases, uveitis, sarcoidosis, inflammatory bowel disease, multiple sclerosis.
10. Evidence or history of other significant cardiac, hepatic, renal, ophthalmologic, psychiatric, or gastrointestinal disease which might increase the risks of participating in the study
11. Active bacterial, viral or fungal infections.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: hTERT/GM-CSF+PCV, T cell infusion; ARM A = hTERT/GM-CSF+PCV, T cell infusion	Biological: hTERT vaccine, GM-CSF, PCV, T cell infusion; hTERT vaccine (multi-peptide vaccine), Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF), Prevnar-Pneumococcal Conjugate vaccine (PCV), T cell infusion
Experimental: GM-CSF+PCV, T cell infusion,GM-CSF+PVC; ARM B GM-CSF+PCV, T cell infusion,GM-CSF+PVC	Biological: GM-CSF, PCV, T cell infusion; Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF), Prevnar-Pneumococcal Conjugate vaccine (PCV), T cell infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary toxicity endpoint	Incidence of delayed hematopoietic recovery and the incidence of Grade 3 or greater autoimmune events	2 yrs

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: University of Maryland, College Park
• Investigators: Study Chair: Carl H June, MD, University of Pennsylvania

Publications and helpful links

General Publications

• Rapoport AP, Aqui NA, Stadtmauer EA, Vogl DT, Fang HB, Cai L, Janofsky S, Chew A, Storek J, Akpek G, Badros A, Yanovich S, Tan MT, Veloso E, Pasetti MF, Cross A, Philip S, Murphy H, Bhagat R, Zheng Z, Milliron T, Cotte J, Cannon A, Levine BL, Vonderheide RH, June CH. Combination immunotherapy using adoptive T-cell transfer and tumor antigen vaccination on the basis of hTERT and survivin after ASCT for myeloma. Blood. 2011 Jan 20;117(3):788-97. doi: 10.1182/blood-2010-08-299396. Epub 2010 Oct 28.

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: January 3, 2008
• First Submitted That Met QC Criteria: February 2, 2009
• First Posted (Estimate): February 3, 2009

Study Record Updates

• Last Update Posted (Actual): October 23, 2019
• Last Update Submitted That Met QC Criteria: October 21, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Sargramostim; Molgramostim
• Other Study ID Numbers: UPCC 13406 / GCC610

Plan for Individual participant data (IPD)

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