Combination Immunotherapy and Autologous Stem Cell Transplantation for Myeloma

This study is currently recruiting participants.
Verified April 2013 by Abramson Cancer Center of the University of Pennsylvania
Sponsor:
Collaborator:
University of Pennsylvania
Information provided by (Responsible Party):
Abramson Cancer Center of the University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT01245673
First received: November 19, 2010
Last updated: April 2, 2013
Last verified: April 2013
  Purpose

One purpose of this study is to find out if a new combination of immune system treatments (MAGE-A3 vaccine plus activated T-cells) will allow the body to build up protection ("immunity") against the myeloma cells. A second purpose is to find out how well this combination of immune system treatments is able to control the myeloma.


Condition Intervention Phase
Advanced Myeloma.
Biological: Prevnar- Pneumococcal Conjugate Vaccine (PCV)
Other: Activated/costimulated autologous T-cell
Drug: Lenalidomide
Biological: MAGE-A3, Hiltonol® (Poly-ICLC)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Combination Immunotherapy After ASCT for Advanced Myeloma to Study MAGE-A3 Immunizations With Hiltonol® (Poly-ICLC) Plus Transfer of Vaccine-Primed Autologous T Cells Followed by Lenalidomide Maintenance

Resource links provided by NLM:


Further study details as provided by Abramson Cancer Center of the University of Pennsylvania:

Primary Outcome Measures:
  • T-Cell responses against the MAGE-3 vaccine [ Time Frame: At day 100 post transplant ] [ Designated as safety issue: Yes ]
    T-cell responses against the MAGE-A3 vaccine as measured by proliferation & intracellular cytokine assays, at D100 post-transplant is the primary immunological endpoint.

  • Change in Paraprotein Levels [ Time Frame: 180 Days Post-Transplant ] [ Designated as safety issue: Yes ]
    We will also compare the paraprotein levels in the blood or urine by SPEP/UPEP and serum free light chain analyses at day 100 post-transplant to the levels at day +180 post-transplant. We would like to demonstrate that the overall response rate (PR + near-CR + CR) is > 20% greater at day +180 than at day +100.


Secondary Outcome Measures:
  • MAGE-A3 Immune Responses [ Time Frame: Day 180 post-transplant ] [ Designated as safety issue: Yes ]
    A secondary endpoint will be the comparison of MAGE-A3 immune responses at day 180 post-transplant vs day 100 post-transplant to evaluate immune potentiation effect of lenalidomide.


Estimated Enrollment: 28
Study Start Date: November 2010
Estimated Study Completion Date: November 2013
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: Prevnar- Pneumococcal Conjugate Vaccine (PCV)
    On day +2 all patients will receive ~ 5 x 10e10 costimulated T-cells which have been primed in vivo with MAGE-A3/ Hiltonol® and PCV.
    Other: Activated/costimulated autologous T-cell
    For all patients, the cells will be expanded ex vivo for up to 12 days and then prepared for infusion ~day 2 post-transplant. The target number of costimulated T-cells for infusion will be ~ 5 x 10e10 T-cells total in 100-500 mL total volume. On the designated infusion date, the T-cells will be harvested.
    Drug: Lenalidomide
    At about day 100 post-transplant, after completion of post-transplant immunological assessments and myeloma restaging studies, patients will be eligible to receive low-dose lenalidomide for maintenance therapy (10 mg/day) until progression of myeloma or development of intolerance.
    Biological: MAGE-A3, Hiltonol® (Poly-ICLC)
    After study enrollment, patients will receive both MAGE-A3/GM-CSF [+ coinjection of 2mg of Hiltonol®(Poly-ICLC)]
Detailed Description:

Autologous stem cell transplant (ASCT) can lead to a complete or partial disappearance of the myeloma in about 2 out of 3 patients. However, an ASCT only sometimes leads to a cure of the myeloma. In about half the patients the myeloma comes back after about 1-2 years. In about 90% of patients it comes back by about 10 years after transplant.

One possible way to improve upon the results of ASCT for myeloma is to help the body's defense or immune system recover faster after transplant. Another way is to teach the body's immune system to fight against the myeloma cells.

In two earlier research studies which included more than 100 patients, certain types of immune cells called "T cells" or "T lymphocytes" were taken out of a patient's body using a procedure called "apheresis". These cells were then grown up in the lab. After the transplant, these T cells were put back into the patients. The replaced T cells helped the patients'immune systems to recover faster after the transplant. In addition, when the T cells were given back to patients they also received a vaccination. The vaccination or injection was for a certain type of pneumonia germ called "pneumococcus". We found that most patients built up protection against this pneumonia-causing germ. In another study, we used a possible myeloma cancer vaccine. However, we found that less than half the patients responded to this vaccine.

In this new study, we want to test a different type of myeloma cancer vaccine. This different cancer vaccine is based on a protein called MAGE-A3. The MAGE-A3 protein is found in about 50% of cases of myeloma. This vaccine consists of small pieces of protein (called "peptides") which come from the MAGE-A3 protein. In order to help the immune system respond better we will add two new steps. First we will add an immune system stimulant called "Hiltonol®" to each vaccination. Hiltonol® is a chemical substance that turns on several parts of the immune system. It may make the immune system better able to respond to the vaccine. It has been tested in several hundred patients and has been used with about a dozen different types of cancer and germ vaccines. Second, starting about 100 days after the transplant procedure, patients will get a medicine called Lenalidomide. Lenalidomide is already approved by the Food and Drug Administration (FDA) for treatment of myeloma. In this study, we want to know whether Lenalidomide could help to improve the body's ability to respond to the vaccinations and help to treat the myeloma itself.

  Eligibility

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

Inclusion Criteria:

  • Written informed consent
  • Patients must be registered with the Sponsor's Monitor
  • Patients must have a diagnosis of myeloma
  • Patients must meet one of the following criteria:

    1. 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).
    2. 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.
    3. 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 (> or = to 3 abnormalities),t(4;14),t(14;16),del (17)(p13.1),and/or chromosome 13 abnormalities.
  • Patients must have measurable disease on study entry
  • Patients must be between ages 18-80 (inclusive).
  • Patients should have adequate vital organ function as defined by the protocol.
  • ECOG performance status 0-2 (unless due solely to bone pain)
  • 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®.
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test as per the protocol
  • Lenalidomide 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).

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 + Hepatitis B surface antigen); + Hepatitis C virus (HCV) antibody is NOT an exclusion
  • 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 would likely 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: NCT01245673

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

Locations
United States, Maryland
University of Maryland Greenebaum Cancer Center Recruiting
Baltimore, Maryland, United States, 21201
Contact: Sunita Philip, MPH    410-328-8199    sphilip1@umm.edu   
Principal Investigator: Aaron P. Rapoport, M.D.         
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania Completed
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Abramson Cancer Center of the University of Pennsylvania
University of Pennsylvania
Investigators
Study Chair: Aaron Rapoport, M.D. University of Maryland Greenebaum Cancer Center
Principal Investigator: Ed Stadtmauer, MD Abramson Cancer Center of the University of Pennsylvania
  More Information

No publications provided

Responsible Party: Abramson Cancer Center of the University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01245673     History of Changes
Other Study ID Numbers: UPCC 02710, UMGCC 0955
Study First Received: November 19, 2010
Last Updated: April 2, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Abramson Cancer Center of the University of Pennsylvania:
Advanced Disease
MAGE-A3 Immunizations with Hiltonol
Vaccine-Primed Autologous T-Cells
Lenalidomide Maintenance

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
Poly ICLC
Thalidomide
Lenalidomide
Interferon Inducers
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances

ClinicalTrials.gov processed this record on April 17, 2014