Combination Immunotherapy and Autologous Stem Cell Transplantation for Myeloma

NCT01245673 | Completed Phase 2 Results DMC

• 2 other identifiers: UPCC 02710UMGCC 0955
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 2

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.

Conditions

Myeloma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Between day 100 and 180 post transplant

Study Arms (1)

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.

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

Interventions

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).

Prevnar, T Cells, Lenalidomide, MAGE A-3

Activated/costimulated autologous T-cell OTHER

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.

Prevnar, T Cells, Lenalidomide, MAGE A-3

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.

Prevnar, T Cells, Lenalidomide, MAGE A-3

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).

Prevnar, T Cells, Lenalidomide, MAGE A-3

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (2)

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• 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.

  PMID: 24520093 DERIVED

MeSH Terms

Conditions

Neoplasms, Plasma Cell

Interventions

Heptavalent Pneumococcal Conjugate Vaccine; Lenalidomide; poly ICLC

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Pneumococcal Vaccines; Streptococcal Vaccines; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures; Vaccines, Combined; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Liz Veloso
• Organization: University of Pennsylvania

eveloso@pennmedicine.upenn.edu

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Study Officials

• Aaron Rapoport, M.D.

  University of Maryland Greenebaum Cancer Center

  STUDY CHAIR

• Ed Stadtmauer, MD

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2010
• First Posted: November 22, 2010
• Study Start: May 10, 2011
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2018
• Last Updated: April 6, 2020
• Results First Posted: March 19, 2020

Record last verified: 2020-03

Locations

US (2)