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

NCT ID: NCT00834665

Last Updated: 2019-10-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-12-31
• Study Completion Date: 2017-12-31

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.

Conditions

Multiple Myeloma

Study Design

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

Study Groups

hTERT/GM-CSF+PCV, T cell infusion

ARM A = hTERT/GM-CSF+PCV, T cell infusion

Group Type: EXPERIMENTAL

hTERT vaccine, GM-CSF, PCV, T cell infusion

Intervention Type: BIOLOGICAL

hTERT vaccine (multi-peptide vaccine), Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF), Prevnar-Pneumococcal Conjugate vaccine (PCV), T cell infusion

GM-CSF+PCV, T cell infusion,GM-CSF+PVC

ARM B GM-CSF+PCV, T cell infusion,GM-CSF+PVC

Group Type: EXPERIMENTAL

GM-CSF, PCV, T cell infusion

Intervention Type: BIOLOGICAL

Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF), Prevnar-Pneumococcal Conjugate vaccine (PCV), T cell infusion

Interventions

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

Intervention Type: BIOLOGICAL

GM-CSF, PCV, T cell infusion

Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF), Prevnar-Pneumococcal Conjugate vaccine (PCV), T cell infusion

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Maryland, College Park

OTHER

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carl H June, MD

Role: STUDY_CHAIR

University of Pennsylvania

Locations

Greenbaum Cancer Center

Baltimore, Maryland, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 21030558 (View on PubMed)

Other Identifiers

UPCC 13406 / GCC610

Identifier Type: -

Identifier Source: org_study_id