MyelomaPhase 2NCT01245673

Combination Immunotherapy and Autologous Stem Cell Transplantation for Myeloma

A Phase 2 study testing Prevnar- Pneumococcal Conjugate Vaccine (PCV), Activated/costimulated autologous T-cell and Revlamid® (Lenalidomide) in people with Myeloma, run by University of Pennsylvania at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Myeloma
What is being tested?: Prevnar- Pneumococcal Conjugate Vaccine (PCV), Activated/costimulated autologous T-cell and Revlamid® (Lenalidomide)
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 28 participants
Where: 2 sitesUnited States
Study dates: 10 May 2011to Dec 2018
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

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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).

Who cannot join

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

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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.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

University of Maryland Greenebaum Cancer Center
Baltimore, Maryland, 21201
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

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

Read the 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.

Conditions: Myeloma
Being tested: Prevnar- Pneumococcal Conjugate Vaccine (PCV), Activated/costimulated autologous T-cell, Revlamid® (Lenalidomide), MAGE-A3/GM-GSF, Hiltonol® (Poly-ICLC)
Keywords: Advanced Disease, MAGE-A3 Immunizations with Hiltonol, Vaccine-Primed Autologous T-Cells, Lenalidomide Maintenance
Medical subject headings: Neoplasms, Plasma Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Prevnar- Pneumococcal Conjugate Vaccine (PCV)Biological
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).
Activated/costimulated autologous T-cellOther
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.
Revlamid® (Lenalidomide)Drug
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.
MAGE-A3/GM-GSF, Hiltonol® (Poly-ICLC)Biological
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).

Study groups in NCT01245673
Study group	Role	What they receive
Prevnar, T Cells, Lenalidomide, MAGE A-3	Experimental	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. Receives: Biological: Prevnar- Pneumococcal Conjugate Vaccine (PCV); Other: Activated/costimulated autologous T-cell; Drug: Revlamid® (Lenalidomide); Biological: MAGE-A3/GM-GSF, Hiltonol® (Poly-ICLC)

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Between day 100 and 180 post transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

10 May 2011Dec 2018

First posted22 Nov 2010 (estimated)
Study start10 May 2011
Primary completionDec 2015
Study completionDec 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for MyelomaStudies of the same condition, open and under way.
More trials run by University of PennsylvaniaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 28 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01245673
Sponsor's protocol ID: UPCC 02710
Other IDs: UMGCC 0955
Status last verified: Mar 2020
First submitted: 19 Nov 2010
Last updated: 6 Apr 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 24520093

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Myeloma trials

Study at a glance

From the registry record, last updated by the sponsor on 6 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01245673
Acronym / sponsor ID: UPCC 02710
Conditions: Myeloma
Keywords: Advanced Disease, MAGE-A3 Immunizations with Hiltonol, Vaccine-Primed Autologous T-Cells, Lenalidomide Maintenance
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 28 participants (actual)
Lead sponsor: University of PennsylvaniaUniversity, hospital or other
Study start: 10 May 2011 (actual)
Primary completion: Dec 2015 (actual)
Study completion: Dec 2018 (actual)
First posted: 22 Nov 2010 (estimated)
Results: Posted 19 Mar 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Prevnar, T Cells, Lenalidomide, MAGE A-3	Experimental	Biological: Prevnar- Pneumococcal Conjugate Vaccine (PCV), Other: Activated/costimulated autologous T-cell, Drug: Revlamid® (Lenalidomide), Biological: MAGE-A3/GM-GSF, Hiltonol® (Poly-ICLC)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.

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (14 listed)

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:
Patients must have measurable disease on study entry

Key exclusion criteria (11 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Prevnar- Pneumococcal Conjugate Vaccine (PCV)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).	Biological	Prevnar, T Cells, Lenalidomide, MAGE A-3
Activated/costimulated autologous T-cellFor 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.	Other	Prevnar, T Cells, Lenalidomide, MAGE A-3
Revlamid® (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 Revlamid® (Lenalidomide) 10 mg/day for maintenance therapy (10 mg/day) until progression of myeloma or development of intolerance.	Drug	Prevnar, T Cells, Lenalidomide, MAGE A-3
MAGE-A3/GM-GSF, Hiltonol® (Poly-ICLC)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).	Biological	Prevnar, T Cells, Lenalidomide, MAGE A-3

Primary outcome

Primary Myeloma Endpoint
Time frame: Between day 100 and 180 post transplant
To determine whether lenalidomide maintenance plus the late booster immunizations leads to improved myeloma clinical responses between day 180 and day 100 post-transplant.

Results and safety

Results posted to the registry on 19 Mar 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
MAGE A-3, GM-CSF, Hiltonol®, T Cells, Lenalidomide,	28	27

Primary outcome: Primary Myeloma Endpoint

Time frame: Between day 100 and 180 post transplant. Count of participants. Unit: Participants

Measure	Prevnar, T Cells, Lenalidomide, MAGE A-3 n = 26
Subjects in CR D100 and D180	4
Subjects in sCR D100 and 180	1
Subjects in VGPR D100 and D180	1
Subjects in PR D100 and D180	5
Subjects with SD at D+100 and 180	3
Subjects with improved response at D100 and D180	6
Subjects with poorer response at D100 and D180	4
Subjects with no disease response reported	2

Population analysed: Subjects that reached D100 and D180

Adverse events

Time frame: Adverse event reporting begins at the time of T-cell harvest and continues until day 180 post infusion.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Prevnar, T Cells, Lenalidomide, MAGE A-3	9 of 27 (33.3%)	27 of 27 (100%)	0 of 27

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 24520093Rapoport 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.

Related trials for Myeloma

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Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
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RecruitingPhase 2
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Active, not recruitingPhase 3
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Aaron Rapoport, M.D. study chair

University of Maryland Greenebaum Cancer Center

Ed Stadtmauer, MD principal investigator

Abramson Cancer Center at Penn Medicine

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Primary Myeloma Endpoint (time frame: Between day 100 and 180 post transplant). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01245673, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2020.