Combination Immunotherapy and Autologous Stem Cell Transplantation for Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01245673
Recruitment Status : Active, not recruiting
First Posted : November 22, 2010
Last Update Posted : December 20, 2017
Information provided by (Responsible Party):
University of Pennsylvania

Brief Summary:
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 or disease Intervention/treatment Phase
Myeloma Biological: Prevnar- Pneumococcal Conjugate Vaccine (PCV) Other: Activated/costimulated autologous T-cell Drug: Lenalidomide Biological: MAGE-A3, Hiltonol® (Poly-ICLC) Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : April 2011
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : August 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Prevnar, T Cells, Lenalidomide, MAGE A-3 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)]

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

  2. Change in Paraprotein Levels [ Time Frame: 180 Days Post-Transplant ]
    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 :
  1. MAGE-A3 Immune Responses [ Time Frame: Day 180 post-transplant ]
    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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01245673

United States, Maryland
University of Maryland Greenebaum Cancer Center
Baltimore, Maryland, United States, 21201
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
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

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: University of Pennsylvania Identifier: NCT01245673     History of Changes
Other Study ID Numbers: UPCC 02710
UMGCC 0955 ( Other Identifier: University of Maryland Greenebaum Cancer Center )
First Posted: November 22, 2010    Key Record Dates
Last Update Posted: December 20, 2017
Last Verified: December 2017

Keywords provided by 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
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Heptavalent Pneumococcal Conjugate Vaccine
Poly I-C
Carboxymethylcellulose Sodium
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Immunosuppressive Agents
Leprostatic Agents