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Combination Immunotherapy and Autologous Stem Cell Transplantation for Myeloma

Primary Purpose

Myeloma

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Prevnar- Pneumococcal Conjugate Vaccine (PCV)

Activated/costimulated autologous T-cell

Revlamid® (Lenalidomide)

MAGE-A3/GM-GSF, Hiltonol® (Poly-ICLC)

About this trial

This is an interventional treatment trial for Myeloma focused on measuring Advanced Disease, MAGE-A3 Immunizations with Hiltonol, Vaccine-Primed Autologous T-Cells, Lenalidomide Maintenance

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of Maryland Greenebaum Cancer Center
Abramson Cancer Center of the University of Pennsylvania

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Prevnar, T Cells, Lenalidomide, MAGE A-3

Arm Description

All patients will receive a priming immunization with a MAGE-A3/GM-CSF vaccine with adjuvant Hiltonol® (Poly-ICLC) along with the pneumococcal conjugate vaccine/PCV control vaccine about 10 days before a steady-state mononuclear cell apheresis. Patients will then undergo hematopoietic stem cell mobilization. All patients will receive high-dose melphalan followed by hematopoietic stem cells on day 0. On day +2, patients will receive anti-CD3/anti-CD28-costimulated autologous T cells. At days 14, 42, and 90, patients will receive MAGEA3/GM-CSF (+Hiltonol® Poly-ICLC) and PCV booster immunizations followed by restaging studies and immune assessments at day +100. At day 100, after immunizations and restaging, patients will start Revlamid® (Lenalidomide) maintenance therapy followed by 2 additional MAGE-A3 and PCV immunizations at days 120 and 150.

Outcomes

Primary Outcome Measures

Primary Myeloma Endpoint

To determine whether lenalidomide maintenance plus the late booster immunizations leads to improved myeloma clinical responses between day 180 and day 100 post-transplant.

Secondary Outcome Measures

Full Information

NCT ID

NCT01245673

First Posted

November 19, 2010

Last Updated

March 19, 2020

Sponsor

University of Pennsylvania

1. Study Identification

Unique Protocol Identification Number

NCT01245673

Brief Title

Combination Immunotherapy and Autologous Stem Cell Transplantation for Myeloma

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 Type

Interventional

2. Study Status

Record Verification Date

March 2020

Overall Recruitment Status

Completed

Study Start Date

May 10, 2011 (Actual)

Primary Completion Date

December 2015 (Actual)

Study Completion Date

December 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Pennsylvania

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Myeloma

Keywords

Advanced Disease, MAGE-A3 Immunizations with Hiltonol, Vaccine-Primed Autologous T-Cells, Lenalidomide Maintenance

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

28 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Prevnar, T Cells, Lenalidomide, MAGE A-3

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Prevnar- Pneumococcal Conjugate Vaccine (PCV)

Intervention Description

After study enrollment, patients will receive Prevnar- Pneumococcal Conjugate Vaccine (PCV). At Day #14, Day #42, and Day #90, Day #120 and Day #150, patients will receive a booster immunization with Prevnar- Pneumococcal Conjugate Vaccine (PCV).

Intervention Type

Other

Intervention Name(s)

Activated/costimulated autologous T-cell

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Revlamid® (Lenalidomide)

Intervention Description

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 Revlamid® (Lenalidomide) 10 mg/day for maintenance therapy (10 mg/day) until progression of myeloma or development of intolerance.

Intervention Type

Biological

Intervention Name(s)

MAGE-A3/GM-GSF, Hiltonol® (Poly-ICLC)

Intervention Description

After study enrollment, patients will receive both MAGE-A3/GM-CSF [+ coinjection of 2mg of Hiltonol®(Poly-ICLC)]. At Day #14, Day #42, Day #90, Day #120 and Day #150 patients will receive an additional immunization with MAGE-A3/GM-GSF, Hiltonol® (Poly-ICLC).

Primary Outcome Measure Information:

Title

Primary Myeloma Endpoint

Description

To determine whether lenalidomide maintenance plus the late booster immunizations leads to improved myeloma clinical responses between day 180 and day 100 post-transplant.

Time Frame

Between day 100 and 180 post transplant

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility 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: 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). 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 (> 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Aaron Rapoport, M.D.

Organizational Affiliation

University of Maryland Greenebaum Cancer Center

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Ed Stadtmauer, MD

Organizational Affiliation

Abramson Cancer Center at Penn Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Maryland Greenebaum Cancer Center

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21201

Country

United States

Facility Name

Abramson Cancer Center of the University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

24520093

Citation

Rapoport AP, Aqui NA, Stadtmauer EA, Vogl DT, Xu YY, Kalos M, Cai L, Fang HB, Weiss BM, Badros A, Yanovich S, Akpek G, Tsao P, Cross A, Mann D, Philip S, Kerr N, Brennan A, Zheng Z, Ruehle K, Milliron T, Strome SE, Salazar AM, Levine BL, June CH. Combination immunotherapy after ASCT for multiple myeloma using MAGE-A3/Poly-ICLC immunizations followed by adoptive transfer of vaccine-primed and costimulated autologous T cells. Clin Cancer Res. 2014 Mar 1;20(5):1355-65. doi: 10.1158/1078-0432.CCR-13-2817. Epub 2014 Feb 11.

Results Reference

derived

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Combination Immunotherapy and Autologous Stem Cell Transplantation for Myeloma

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