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

Phase 1/Phase 2
18 Years
80 Years
Open (Enrolling)
Multiple Myeloma

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Trial Information

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

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.

Inclusion Criteria

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

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

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.

Type of Study:


Study Design:

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

Outcome Measure:

Does combination therapy delay hematopoietic recovery or induce other autoimmune events.

Outcome Time Frame:

2 yrs

Safety Issue:


Principal Investigator

Carl H June, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of Pennsylvania


United States: Food and Drug Administration

Study ID:

UPCC 13406 / GCC610



Start Date:

December 2006

Completion Date:

December 2015

Related Keywords:

  • Multiple Myeloma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell



University of PennsylvaniaPhiladelphia, Pennsylvania  19104
Greenbaum Cancer CenterBaltimore, Maryland  21201-1595