Dendritic Cell Vaccine + Standard Therapy for Glioblastoma

(DERIVe Trial)

Overseen By Stevie Threatt, RN, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Annick Desjardins, MD

Must be taking: Corticosteroids

Must not be taking: Immuno-suppressive agents

Disqualifiers: Pregnancy, HIV, Hepatitis C, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

43 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that co-medication that may interfere with study results, such as immuno-suppressive agents other than corticosteroids, is not allowed. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

What data supports the effectiveness of this treatment for glioblastoma?

Research shows that using dendritic cell vaccines targeting cytomegalovirus pp65, combined with temozolomide, can extend survival in glioblastoma patients. In one study, patients receiving this combination had a median progression-free survival of 25.3 months and overall survival of 41.1 months, which is longer than typical outcomes for this condition. ^{1 2 3 4 5}

Is the dendritic cell vaccine with temozolomide safe for humans?

The dendritic cell vaccine combined with temozolomide has shown some safety concerns, including a severe immune reaction in one patient, but generally, temozolomide does not impair the function of immune cells. Removing certain components from the vaccine can help avoid adverse reactions. ^{1 2 3 4 5}

What makes the dendritic cell vaccine treatment for glioblastoma unique?

This treatment combines a dendritic cell vaccine, which helps the immune system recognize and attack cancer cells, with the standard chemotherapy drug temozolomide. Unlike traditional treatments, it uses a personalized approach by pulsing the vaccine with a patient's own tumor material, potentially enhancing the immune response against glioblastoma. ^{1 3 4 6 7}

What is the purpose of this trial?

Patients with newly diagnosed glioblastoma will be consented following tumor resection then undergo leukapheresis for harvest of peripheral blood leukocytes for generation of dendritic cells. Subjects will then receive standard of care (planned 6 weeks) radiation therapy (RT) and concurrent temozolomide (TMZ) at a standard targeted dose of 75 mg/m2/day. The study cycle of TMZ comprises a targeted dose of 150-200mg/m2/day for 5 days every 4 (+2) weeks for up to 12 cycles (patients with unmethylated MGMT gene promoter will receive only cycle 1). All patients will receive up to a total of 10 DC vaccines called pp65 CMV dendritic cells (DC). Dendritic Cell (DC) vaccines #1-3 will be given every two weeks, thus delaying the initiation of TMZ cycle 2 for patients receiving TMZ. All remaining TMZ/vaccine cycles will be 4 (+2) weeks in length. After the first 3 DC vaccines given during Cycle 1 of TMZ, the remaining DC vaccine injections are given on Day 21 (+/- 2 days) of each TMZ cycle. Subjects with unmethylated MGMT will only receive one cycle of adjuvant TMZ; however, their vaccine schedule will follow the same 4 (+ 2) week TMZ cycle schedule. Following RT, patients will be randomized into 1 of 3 groups. Groups 1 and 2 will be blinded. The groups differ in the type of pre-conditioning received prior to DC vaccine #4; additionally, Group 3 will be receiving infusions of varlilumab 7 days prior to and with vaccine #1 and 7 days prior to vaccine #3+. The pre-conditioning for each group is as follows: Group 1: Unpulsed DC pre-conditioning prior to DC vaccine #4; Group 2: Tetanus-diphtheria (Td) pre-conditioning prior to DC vaccine #4; Group 3: Td pre-conditioning prior to DC vaccine #4 and varlilumab infusion at 7 days prior to each DC vaccine (except DC vaccine #2) with Td pre-conditioning prior to vaccine #4.

Research Team

Annick Desjardins, MD, FRCPC

Principal Investigator

Duke University

Eligibility Criteria

Adults with glioblastoma who've had a tumor resection, meet certain health criteria (like KPS ≥ 70%, specific blood cell counts), are not pregnant or breastfeeding, agree to use effective contraception, and can undergo standard radiation/chemotherapy. Excluded are those with severe allergies, metal implants preventing MRI, other cancers needing active treatment, certain infections or heart conditions.

Inclusion Criteria

I had surgery for glioblastoma and my latest scans show a small remaining area of less than 1 cm.

My MRI after radiation shows no cancer spread outside the treated area.

My kidney and liver tests are within acceptable limits for my age.

Exclusion Criteria

I am not using birth control and can become pregnant or cause pregnancy.

I cannot have an MRI due to my weight or because I have certain metal implants.

My cancer has spread to my brain.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation and Concurrent Chemotherapy

Participants receive standard of care radiation therapy and concurrent temozolomide for 6 weeks

6 weeks

Weekly visits for radiation therapy

Adjuvant Chemotherapy and DC Vaccination

Participants receive temozolomide cycles and dendritic cell vaccines. DC vaccines #1-3 are given every 2 weeks, delaying TMZ cycle 2. Remaining cycles are 4 weeks long.

Up to 48 weeks

Bi-weekly visits initially, then monthly

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• Human CMV pp65-LAMP mRNA-pulsed autologous DCs
• Td
• Temozolomide
• Unpulsed DCs
• Varlilumab

Trial Overview The trial tests dendritic cell vaccines in glioblastoma patients post-surgery. Patients receive standard radiation and temozolomide chemotherapy plus up to 10 DC vaccines. They're randomized into groups receiving different pre-conditioning before the fourth vaccine; one group also gets varlilumab infusions.

Participant Groups

Group I: Gr3:DC Vaccine+varlilumab(Td pre-conditioning) Experimental Treatment 4 Interventions

Patients will receive TMZ at a target dose of 150-200 mg/m\^2/d for 5 days every 4 (+2) weeks for up to 12 cycles. DC vaccines will be administered in equal amounts to both inguinal regions. DC vaccines #1-3 occur every 2 weeks and all subsequent vaccines (up to 10) occur monthly. Group 3 patients will receive the first 3 DC vaccines every 2 weeks, same as Groups 1 and 2, but they will also receive varlilumab intraveneously (IV) 7 days before vaccine #1 and again at the same visit as vaccine #1, as well as 7 days before every DC vaccine except vaccine #2. Prior to the 4th vaccine, patients will receive a single dose of Td toxoid administered to a single side of the groin and saline administered to the contralateral side.

Group II: Gr2: DC Vaccine (Td pre-conditioning) Experimental Treatment 3 Interventions

Patients will receive TMZ at a target dose of 150-200 mg/m\^2/d for 5 days every 4 (+2) weeks for up to 12 cycles. DC vaccines will be administered in equal amounts to both inguinal regions. DC vaccines #1-3 occur every 2 weeks and all subsequent vaccines (up to 10) occur monthly. Group 2 patients will receive a single dose of Td toxoid administered to a single side of the groin and saline administered to the contralateral side the day prior to the 4th DC vaccine, which is always given bilaterally at the groin site.

Group III: Gr1: DC vaccine (DC pre-conditioning) Experimental Treatment 3 Interventions

Patients will receive TMZ at a target dose of 150-200 mg/m\^2/d for 5 days every 4 (+2) weeks for up to 12 cycles. DC vaccines will be administered in equal amounts to both inguinal regions. DC vaccines #1-3 occur every 2 weeks and all subsequent vaccines (up to 10) occur monthly. Group 1 patients will receive autologous unpulsed DC vaccines administered to a single side of the groin and saline administered to the contralateral side the day prior to the 4th DC vaccine as pre-conditioning.

Who Is Running the Clinical Trial?

Annick Desjardins, MD

Lead Sponsor

Trials

3

Recruited

150+

Gary Archer Ph.D.

Lead Sponsor

Trials

12

Recruited

290+

Celldex Therapeutics

Industry Sponsor

Trials

66

Recruited

5,900+

Anthony S. Marucci

Celldex Therapeutics

Chief Executive Officer since 2008

MBA from Columbia University, MHL from Brown University

Diane C. Young

Celldex Therapeutics

Chief Medical Officer since 2019

MD from Harvard Medical School, AB in Biochemical Sciences from Harvard University

References

1. England pubmed.ncbi.nlm.nih.gov

Expansion of effector and memory T cells is associated with increased survival in recurrent glioblastomas treated with dendritic cell immunotherapy. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Long-term Survival in Glioblastoma with Cytomegalovirus pp65-Targeted Vaccination. [2023]

3. Greece pubmed.ncbi.nlm.nih.gov

Therapeutical doses of temozolomide do not impair the function of dendritic cells and CD8+ T cells. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Severe adverse immunologic reaction in a patient with glioblastoma receiving autologous dendritic cell vaccines combined with GM-CSF and dose-intensified temozolomide. [2018]

5. Germany pubmed.ncbi.nlm.nih.gov

Phase I/II trial of combination of temozolomide chemotherapy and immunotherapy with fusions of dendritic and glioma cells in patients with glioblastoma. [2018]

6. England pubmed.ncbi.nlm.nih.gov

First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

A Phase I Study of Autologous Dendritic Cell Vaccine Pulsed with Allogeneic Stem-like Cell Line Lysate in Patients with Newly Diagnosed or Recurrent Glioblastoma. [2022]