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

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

35 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research study is to determine the safety of CT-011 alone, as well as the combination of the Dendritic cell fusion vaccine and CT-011, after autologous stem cell transplantation (ASCT). We are also trying to find out what effect the combination has on the disease, including if it is more successful in preventing or delaying the disease from coming back, compared to treatment with autologous transplantation alone. ASCT is a standard therapy for multiple myeloma that is often successful in significantly decreasing the amount of cancer in the body. CT-011 is an investigational monoclonal antibody. Monoclonal antibodies are a type of drug given by infusion into a vein and are known to target specific cells (in this case, cells in the immune system). The dendritic cell fusion vaccine is an investigational agent that tries to help the immune system to recognize and fight against cancer cells. Unlike a standard vaccine that is used to prevent infections, cancer vaccines are being studied to see if they can fight cancers that are already in the body.

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.

What data supports the effectiveness of the treatment PD-1 Blockade + Dendritic Cell Fusion Vaccine + CT-011 for Multiple Myeloma?

Research shows that the combination of CT-011, an anti-PD-1 antibody, with a dendritic cell/myeloma fusion vaccine can enhance the immune response in patients with multiple myeloma by activating T-cells, which are crucial for fighting cancer. Additionally, blocking the PD-1/PD-L1 pathway has been shown to improve survival in myeloma models, suggesting that this approach may help the immune system better target and destroy cancer cells. ^{1 2 3 4 5}

Is the combination of PD-1 Blockade, Dendritic Cell Fusion Vaccine, and CT-011 generally safe for humans?

The combination of PD-1 blockade with CT-011 and dendritic cell fusion vaccine has been studied in multiple myeloma, showing enhanced immune responses without specific safety concerns mentioned in the provided studies. However, caution is advised as combining checkpoint inhibitors with certain drugs increased the risk of death in myeloma patients, highlighting the need for careful monitoring. ^{1 2 4 6 7}

How is the treatment with PD-1 Blockade, Dendritic Cell Fusion Vaccine, and CT-011 unique for multiple myeloma?

This treatment is unique because it combines a vaccine made from a patient's own tumor cells and immune cells (dendritic cells) with CT-011, an antibody that blocks PD-1, a protein that can suppress the immune system. This combination aims to enhance the body's immune response against multiple myeloma by activating T-cells to better recognize and attack cancer cells. ^{1 2 8 9 10}

Research Team

David Avigan, MD

Principal Investigator

Beth Israel Deaconess Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

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

PD-1 blockade by CT-011, anti-PD-1 antibody, enhances ex vivo T-cell responses to autologous dendritic cell/myeloma fusion vaccine. [2021]

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

Randomized Phase II Trial of Dendritic Cell/Myeloma Fusion Vaccine with Lenalidomide Maintenance after Upfront Autologous Hematopoietic Cell Transplantation for Multiple Myeloma: BMT CTN 1401. [2023]

3. China pubmed.ncbi.nlm.nih.gov

[Expression and Significance of PD-1, PD-L1 and CTLA-4 in the Bone Marrow of Patients with Multiple Myeloma]. [2022]

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

Immunosuppressive effects of multiple myeloma are overcome by PD-L1 blockade. [2022]

5. United States 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. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

The challenges of checkpoint inhibition in the treatment of multiple myeloma. [2020]

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

The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti-PD-1 antibody. [2022]

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

Cellular and vaccine immunotherapy for multiple myeloma. [2023]

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

Vaccination with dendritic cell/tumor fusion cells results in cellular and humoral antitumor immune responses in patients with multiple myeloma. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Identification and characterization of HLA-A24-specific XBP1, CD138 (Syndecan-1) and CS1 (SLAMF7) peptides inducing antigens-specific memory cytotoxic T lymphocytes targeting multiple myeloma. [2019]