Redirected Auto T Cells for Advanced Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Adaptimmune
Sponsor:
Collaborators:
University of Maryland Greenebaum Cancer Center
Abramson Cancer Center of the University of Pennsylvania
Information provided by (Responsible Party):
Adaptimmune
ClinicalTrials.gov Identifier:
NCT01352286
First received: May 4, 2011
Last updated: December 4, 2013
Last verified: December 2013
  Purpose

The primary objective is to evaluate the safety and tolerability of autologous genetically modified T cells transduced to express the high affinity of MAGE-A3 TCR in HLA-A1 subjects and the high affinity NYESO-1 TCR in HLA-A2 subjects.


Condition Intervention Phase
Multiple Myeloma
Genetic: Autologous Genetically modified T cells
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Adaptimmune:

Primary Outcome Measures:
  • Evaluate the safety and tolerability of autologous genetically modified T cells [ Time Frame: 3 yrs ] [ Designated as safety issue: Yes ]
    Occurrence of study related adverse events, defined as NCI CTC> grade 4 signs/symptoms, laboratory toxicities and clinical events that are probably or definitely related to study treatment at any time from the infusion until day 180. This will include infusional toxicity, and any toxicity probably or definitely related to the NYESO-1-c259-T


Secondary Outcome Measures:
  • Clinical Response Rate [ Time Frame: at day 180 ] [ Designated as safety issue: Yes ]
    evaluate correlates of treatment efficacy by measuring (i) clinical response rates to treatment and (ii) the appearance of target antigen/MHC loss variants upon disease recurrence, as well as (iii) immunological :parameters associated with product persistence, bioactivity and functionality.


Estimated Enrollment: 26
Study Start Date: April 2011
Estimated Study Completion Date: April 2019
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Autologous Genetically modified T cells
Patients with advanced myeloma and who are candidates for autologous stem cell transplants, or syngeneic stem cell transplants (SSCT), will be eligible. Prior to full screening on this study, patients will undergo prescreening to evaluate HLA-A type and presence of NYESO-1/LAGE antigen. Patients will undergo a steady-state mononuclear cell apheresis for T cell collection, with an optional second collection. Once mononuclear cells have been collected, patients (or donors in the case of SSCT) will then undergo hematopoietic stem cell mobilization. Patients will receive a dose >0.1-1 x 10^10 anti-CD3/anti-CD28-costimulated autologous T cells which have been genetically modified to express high affinity NYESO-1 TCRs.
Genetic: Autologous Genetically modified T cells
Patients receiving autologous genetically modified T cells will undergo myeloma restaging at days +42, +100 and 6 months post infusion and then Q3 months until relapse/progression or until 5 years, whichever comes first.

Detailed Description:

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.

  Eligibility

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

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01352286

Contacts
Contact: Ed Stadtmauer, MD 855-216-0098 PennCancerTrials@emergingmed.com

Locations
United States, Maryland
Greenebaum Cancer Center, University of Maryland Recruiting
Baltimore, Maryland, United States, 21201
Contact: Aaron Rapoport, MD         
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania Active, not recruiting
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Adaptimmune
University of Maryland Greenebaum Cancer Center
Abramson Cancer Center of the University of Pennsylvania
Investigators
Principal Investigator: Ed Stadtmauer, MD Abramson Cancer Center of the University of Pennsylvania
Principal Investigator: Aaron Rapaport, MD University of Maryland Greenebaum Cancer Center
  More Information

No publications provided

Responsible Party: Adaptimmune
ClinicalTrials.gov Identifier: NCT01352286     History of Changes
Other Study ID Numbers: UPCC 01411
Study First Received: May 4, 2011
Last Updated: December 4, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Adaptimmune:
Multiple myeloma
Autologous stem cell transplantation
Received initial treatment previously

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 September 16, 2014