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A Pilot Phase I/II, Dual-Cohort, Two-Site, Clinical Trial Evaluating the Safety and Activity of Redirected Autologous Tcells Expressing a High Affinity TCR Specific for MAGE-A3/6 or NY-ESO-1 Administered Post ASCT in Patients With Advanced Myeloma


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

Thank you

Trial Information

A Pilot Phase I/II, Dual-Cohort, Two-Site, Clinical Trial Evaluating the Safety and Activity of Redirected Autologous Tcells Expressing a High Affinity TCR Specific for MAGE-A3/6 or NY-ESO-1 Administered Post ASCT in Patients With Advanced Myeloma


Purpose of this study is to evaluate the safety and tolerability of autologous genetically
modified T cells. Genetic material is transferred into the subject's previously harvested
autologous T cells to redirect them to target myeloma cells rather than their usual target.
Study subjects must have systemic or multifocal myeloma requiring autologous stem cell
transplantation whose disease has relapsed or incompletely responded to prior therapy or
have high-risk features. Subjects must also have measureable disease on study entry, as
defined by quantifiable or detectable levels of serum or urine paraprotein or elevated serum
free light chains with an abnormal ratio.


Inclusion Criteria:



- Myeloma has relapsed, progressed, or failed to respond after at least one prior
course of therapy (consisting of at least 2 treatment cycles or months of therapy).

- Failure to respond would correspond to a reduction of less than or equal to 25%of the
original, diagnostic serum or urine paraprotein measurement.

- Myeloma has responded partially to initial therapy but a complete response
(immunofixation negative and normal serum free light chain studies) has not developed
after a minimum of 3 cycles or months of initial therapy.

- Myeloma has high risk features as defined by the presence of one or more cytogenetic
abnormalities known to confer a poor outcome even after standard autotransplants:
complex karyotype (greater or equal to 3 abnormalities), t(4;14), t(14;16), del (17)
(p13.1), and/or chromosome 13 abnormalities. These patients may be enrolled even
while in complete or near-complete remission.

Extended disease-free survival after autotransplantation would be unexpected for these
patients and therefore especially meaningful.

- Subjects must have measurable disease on study entry. Measurable disease may include
quantifiable or detectable levels of serum or urine paraprotein. For patients with
minimally secretory disease or non-secretory myeloma on study entry, serum free
lamda or kappa light chain levels or the serum free light chain ratio may be measured
and used for disease monitoring if abnormal.

- Subjects mus have ECOG score of 0-2 (unless due solely to bone pain)

- Female subjects of childbearing potential must have a negative pregnancy test and
both male and female (of childbearing potential) subjects must agree to use reliable
methods of contraception during the study.

- Prior to Lenalidomide maintenance phase, all study participants must be registered
into the mandatory RevAssist program, and be willing and able to comply with the
requirements of RevAssist. Lemalidomide treatment phase: able to take aspirin (81 or
325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use
warfarin or low molecular weight heparin).

- HLA-A1 patients must have confirmed MAGE-A3/6 expression on the marrow biopsy
specimen and HLA-A2 patients must have confirmed expression of NY-ESO-1 (these
determinations will be under a preenrollment screening consent form using criteria
listed below in study procedures.)

Exclusion Criteria:

- Pregnant or nursing females

- HIV or 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 (as defined by positive Hepatitis B surface antigen); positive
Hepatitis C virus (HCV) antibody is NOT an exclusion.

- Prior allogeneic transplant.

- 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 would likely increase the risks of
participating in the study.

- Active bacterial, viral, or fungal infections.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Evaluate the safety and tolerability of autologous genetically modified T cells

Outcome Description:

Monitoring for occurrences of study related adverse events

Outcome Time Frame:

3 yrs

Safety Issue:

Yes

Principal Investigator

Ed Stadtmauer, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Abramson Cancer Center of the University of Pennsylvania

Authority:

United States: Food and Drug Administration

Study ID:

UPCC 01411

NCT ID:

NCT01352286

Start Date:

April 2011

Completion Date:

April 2019

Related Keywords:

  • Multiple Myeloma
  • Multiple myeloma
  • Autologous stem cell transplantation
  • Received initial treatment previously
  • Multiple Myeloma
  • Neoplasms, Plasma Cell

Name

Location

Abramson Cancer Center of the University of PennsylvaniaPhiladelphia, Pennsylvania  19104-4283
Greenebaum Cancer Center, University of MarylandBaltimore, Maryland  21201