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

Sponsor:	University of Pennsylvania
Collaborator:	University of Maryland
Information provided by (Responsible Party):	University of Pennsylvania
ClinicalTrials.gov Identifier:	NCT00834665

Purpose

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.

Condition	Intervention	Phase
Multiple Myeloma	Biological: Telomerase (hTERT vaccine + pneumococcal conjugate vaccine (PCV)) Biological: PCV vaccine	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Multiple Myeloma

U.S. FDA Resources

Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:

Does combination therapy delay hematopoietic recovery or induce other autoimmune events. [ Time Frame: 2 yrs ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Does combination therapy generate cytotoxic T-cell responses to autologous myeloma cells in-vivo. [ Time Frame: 2 yrs ] [ Designated as safety issue: No ]

Estimated Enrollment:	56
Study Start Date:	December 2006
Estimated Study Completion Date:	December 2015
Estimated Primary Completion Date:	December 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: ARM A ARM A Injection 1 and 2 the telomerase vaccination, followed by GM-CSF, which will also be injected at the same site in order to make the vaccinations work better. Injection 3 and 4 (deep part of the skin in the left thigh)- the survivin and CMV vaccination, followed by GM-CSF. Injection 5 - the PCV vaccination.	Biological: Telomerase (hTERT vaccine + pneumococcal conjugate vaccine (PCV)) One vaccination prior to autologous transplant and 3 vaccination after autologous transplant.
Active Comparator: ARM B ARM B Injection 1: PCV vaccination Injection 2 GM-CSF injection Injection 3 : GM-CSF injection	Biological: PCV vaccine Receipt of PCV vaccine and GM-CSF injections prior to autologous transplant and post transplant

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.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00834665

Locations

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

Sponsors and Collaborators

University of Pennsylvania

University of Maryland

Investigators

Study Chair:

Carl H June, MD

University of Pennsylvania

More Information

No publications provided

Responsible Party:	University of Pennsylvania
ClinicalTrials.gov Identifier:	NCT00834665 History of Changes
Other Study ID Numbers:	UPCC 13406 / GCC610
Study First Received:	January 3, 2008
Last Updated:	January 10, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases

Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on May 24, 2012