PD-1 Blockade + Dendritic Cell Fusion Vaccine + CT-011 for Multiple Myeloma

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Beth Israel Deaconess Medical Center

Disqualifiers: Venous thromboembolism, Autoimmune disease, HIV, others

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

Duration: 18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for multiple myeloma, a type of blood cancer. Researchers aim to determine if combining a monoclonal antibody called CT-011 with the Dendritic Cell Fusion Vaccine can more effectively prevent or delay cancer recurrence after autologous stem cell transplantation (ASCT). Participants are divided into two groups: one receives only CT-011, while the other receives both the vaccine and CT-011. Individuals with multiple myeloma who can undergo high-dose chemotherapy and have a specific disease pattern are suitable candidates for the trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that CT-011, a monoclonal antibody treatment, has been studied in people with multiple myeloma. Studies indicate it is generally safe, though its effectiveness can vary. This treatment aims to help the immune system fight cancer cells.

The dendritic cell fusion vaccine, another treatment in this trial, has also been tested in people with multiple myeloma. It was well-tolerated and helped strengthen the immune response against the cancer.

Both treatments have demonstrated promising safety profiles, as they did not cause serious side effects in previous studies. This is encouraging for those considering joining the trial, suggesting the treatments are likely safe based on past research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of PD-1 blockade with dendritic cell fusion vaccine and CT-011 for treating multiple myeloma because it introduces an innovative approach to enhance the immune system's response to cancer cells. Unlike the standard treatments, which often include chemotherapy and stem cell transplants, CT-011 is a monoclonal antibody designed to block PD-1, a protein that helps cancer cells evade the immune system. The dendritic cell fusion vaccine works by stimulating the body's own immune cells to recognize and attack myeloma cells more effectively. This combination aims to boost the immune system's ability to fight the cancer, potentially leading to more durable responses and improved outcomes for patients.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

Research has shown that CT-011, a new type of antibody, could help treat multiple myeloma. It boosts the activity of T-cells, immune cells that find and attack cancer cells. CT-011 also enhances the function of natural killer cells, another type of immune cell, to combat myeloma cells. In this trial, participants in Group 1 will receive CT-011 alone.

Group 2 will test another treatment, the dendritic cell fusion vaccine, which helps the immune system target and fight cancer. Previous studies found that most patients experienced an immune response, and their disease stopped progressing after receiving this vaccine. Participants in Group 2 will receive both the dendritic cell fusion vaccine and CT-011. Together, these treatments aim to strengthen the body’s defense against multiple myeloma. ^{1 4 5 6 7}

Who Is on the Research Team?

David Avigan, MD

Principal Investigator

Beth Israel Deaconess Medical Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with multiple myeloma who are candidates for high-dose chemotherapy and stem cell rescue. They must have a certain level of heart function, specific lab results, measurable disease, and no serious illnesses like significant heart disease or active infections. Pregnant women or those with autoimmune diseases (except stable hypothyroidism) can't join.

Inclusion Criteria

Your heart's pumping ability is greater than 45%.

Your test results need to match the study's requirements.

Patients with multiple myeloma who may be considered for intensive chemotherapy followed by stem cell transplant.

Exclusion Criteria

You have had a serious blood clot in a vein in the past.

You have a serious autoimmune disease.

You have HIV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-3 months

Initial Therapy and Stem Cell Transplantation

Participants receive standard therapy to reduce multiple myeloma cells, followed by high dose chemotherapy and autologous stem cell transplantation

Several weeks

Treatment

Participants receive 3 infusions of CT-011 at 6 week intervals. Group 2 also receives Dendritic Cell Fusion Vaccine one week after each CT-011 infusion

18 weeks

Weekly visits for monitoring and tests

Follow-up

Participants are monitored with blood tests, urine tests, bone marrow aspirate/biopsy, and skeletal survey at one, three, and six months following the last study treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• CT-011
• Dendritic Cell Fusion Vaccine

Trial Overview The study is testing the safety and effect of CT-011 alone and combined with a dendritic cell fusion vaccine after autologous stem cell transplantation in multiple myeloma patients. It aims to see if this combination helps prevent or delay cancer recurrence better than standard therapy.

How Is the Trial Designed?

Group I: Group 1 Active Control 1 Intervention

Monoclonal antibody CT-011 will be given 1-3 months following autologous transplant. 3 doses will be given at 6 week intervals.

Group II: Group 2 Active Control 2 Interventions

Vaccination with DC/myeloma fusion cells will be given 1-3 months following autologous transplant. Vaccination will be given at 6 weeks intervals. The monoclonal antibody CT-011 will be given 1 week following each vaccination. 3 doses of CT-011 will be given at 6 week intervals.

Who Is Running the Clinical Trial?

Beth Israel Deaconess Medical Center

Lead Sponsor

Trials

872

Recruited

12,930,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Brigham and Women's Hospital

Collaborator

Trials

1,694

Recruited

14,790,000+

Dana-Farber Cancer Institute

Collaborator

Trials

1,128

Recruited

382,000+

Rambam Health Care Campus

Collaborator

Trials

513

Recruited

350,000+

Gateway for Cancer Research

Collaborator

Trials

47

Recruited

2,500+

Published Research Related to This Trial

The novel PD-1 B-cell peptide vaccine (PD1-Vaxx) demonstrated superior efficacy compared to standard anti-PD-1 monoclonal antibodies in preclinical mouse models of colon carcinoma, suggesting it may be a promising alternative for cancer treatment.

Combining PD1-Vaxx with a HER-2 peptide vaccine resulted in enhanced tumor growth inhibition, and both vaccines showed a favorable safety profile with no observed toxicity or autoimmunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and antitumor efficacy of a novel human PD-1 B-cell vaccine (PD1-Vaxx) and combination immunotherapy with dual trastuzumab/pertuzumab-like HER-2 B-cell epitope vaccines (B-Vaxx) in a syngeneic mouse model. Kaumaya, PTP., Guo, L., Overholser, J., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3142955/

PD-1 blockade by CT-011, anti PD-1 antibody, enhances ex ... We demonstrate that PD-1 expression is increased in T cells of patients with active myeloma, and that CT-011 enhances activated T cell responses following DC/ ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3490105/

The PD-1/PD-L1 axis modulates the natural killer cell ... We demonstrate that CT-011, a novel anti–PD-1 antibody, enhances human NK-cell function against autologous, primary MM cells, seemingly through effects on NK- ...

3. withpower.com withpower.com/trial/phase-3-multiple-myeloma-2-2010-9626f

PD-1 Blockade + Dendritic Cell Fusion Vaccine + CT-011 ... This combination aims to enhance the body's immune response against multiple myeloma by activating T-cells to better recognize and attack cancer cells.

4. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.02749/full

Promises and Pitfalls in the Use of PD-1/PD-L1 Inhibitors ... This review aims to analyze the available preclinical and clinical data on the role of PD-1/PD-L1 inhibitors in MM therapy, focusing on available preliminary ...

5. ehoonline.biomedcentral.com ehoonline.biomedcentral.com/articles/10.1186/s40164-023-00456-5

Immune checkpoint inhibitors for multiple myeloma ... PD-1 blockade by CT-011, anti-PD-1 antibody, enhances ex vivo T-cell responses to autologous dendritic cell/myeloma fusion vaccine. J ...

6. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1323914/pdf

Immune checkpoint blockade in hematological malignancies Multiple early phase studies showed safety but low efficacy of PD-1 ... associated with clinical outcomes of relapsed/refractory multiple myeloma ...

7. nature.com nature.com/articles/s41420-024-01818-6

harnessing the immune system to battle multiple myeloma By blocking the combination of PD-1 and PD-L1, inhibitors restore T-cell killing function against myeloma cells [36]. Furthermore, studies have ...