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

Primary Purpose

Multiple Myeloma

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

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

GM-CSF, PCV, T cell infusion

About this trial

This is an interventional treatment trial for Multiple Myeloma

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Written informed consent must be obtained from all patients before entry into the study
Patients must have a diagnosis of myeloma
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
Patients must have measurable disease on study entry.
Patients must be between ages 18-80 (inclusive).
Patients should have adequate vital organ function.
ECOG performance status 0-2
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:

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

Sites / Locations

Greenbaum Cancer Center
University of Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

hTERT/GM-CSF+PCV, T cell infusion

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

Arm Description

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

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

Outcomes

Primary Outcome Measures

Primary toxicity endpoint

Incidence of delayed hematopoietic recovery and the incidence of Grade 3 or greater autoimmune events

Secondary Outcome Measures

Full Information

NCT ID

NCT00834665

First Posted

January 3, 2008

Last Updated

October 21, 2019

Sponsor

University of Pennsylvania

Collaborators

University of Maryland, College Park

1. Study Identification

Unique Protocol Identification Number

NCT00834665

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2019

Overall Recruitment Status

Completed

Study Start Date

December 2006 (undefined)

Primary Completion Date

December 2017 (Actual)

Study Completion Date

December 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Pennsylvania

Collaborators

University of Maryland, College Park

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is: 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. 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: 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). 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Myeloma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

59 (Actual)

8. Arms, Groups, and Interventions

Arm Title

hTERT/GM-CSF+PCV, T cell infusion

Arm Type

Experimental

Arm Description

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

Arm Title

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

Arm Type

Experimental

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

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

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

GM-CSF, PCV, T cell infusion

Intervention Description

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

Primary Outcome Measure Information:

Title

Primary toxicity endpoint

Description

Incidence of delayed hematopoietic recovery and the incidence of Grade 3 or greater autoimmune events

Time Frame

2 yrs

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Each subject must meet ALL of the following criteria during screening to be enrolled in the study: Written informed consent must be obtained from all patients before entry into the study Patients must have a diagnosis of myeloma 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 Patients must have measurable disease on study entry. Patients must be between ages 18-80 (inclusive). Patients should have adequate vital organ function. ECOG performance status 0-2 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: Pregnant or nursing females HIV, HTLV-1/2 seropositivity Known history of myelodysplasia Known history of chronic active hepatitis or liver cirrhosis (if suspected by laboratory studies, should be confirmed by liver biopsy). Active Hepatitis B Prior autotransplant or allogeneic transplant More than 4 distinct, prior courses of therapy for myeloma History of severe autoimmune disease requiring steroids or other immunosuppressive treatments. Active immune-mediated diseases including: connective tissue diseases, uveitis, sarcoidosis, inflammatory bowel disease, multiple sclerosis. Evidence or history of other significant cardiac, hepatic, renal, ophthalmologic, psychiatric, or gastrointestinal disease which might increase the risks of participating in the study Active bacterial, viral or fungal infections.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Carl H June, MD

Organizational Affiliation

University of Pennsylvania

Official's Role

Study Chair

Facility Information:

Facility Name

Greenbaum Cancer Center

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21201

Country

United States

Facility Name

University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

21030558

Citation

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.

Results Reference

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

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