UB-VV111 + Rapamycin for B-Cell Lymphoma

Recruiting at 5 trial locations

Overseen By Jacob Garcia, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Umoja Biopharma

Disqualifiers: Pregnancy, CNS involvement, HIV, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

106 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is a Phase 1 dose-escalation and dose-confirmation study to evaluate the safety and antitumor activity of UB-VV111. The study will enroll patients with relapsed/refractory large B-cell lymphoma (LBCL) and chronic lymphocytic leukemia (CLL).

Do I need to stop my current medications to join the trial?

The trial information does not specify if 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 drug UB-VV111 + Rapamycin for B-Cell Lymphoma?

Research shows that rapamycin, a component of the treatment, has been effective in inducing cell cycle arrest in lymphoma cells and has shown clinical activity in certain types of lymphoma. Additionally, combining rapamycin with other drugs has led to significant tumor regression in lymphoma models. ^{1 2 3 4 5}

What makes the drug UB-VV111 + Rapamycin unique for treating B-cell lymphoma?

UB-VV111 combined with Rapamycin is unique because it targets the mTOR pathway, which is crucial for cell growth and survival, and enhances the effectiveness of Rapamycin by potentially inducing more apoptosis (cell death) in aggressive B-cell lymphomas. This combination may offer a novel approach by improving the cytotoxic effects compared to using Rapamycin alone. ^{1 2 4 6 7}

Research Team

Jacob Garcia, MD

Principal Investigator

Umoja Biopharma

Eligibility Criteria

This trial is for adults with relapsed or refractory B-cell lymphoma or chronic lymphocytic leukemia. Participants must have measurable disease, be in good general health without serious diseases or active infections, and have a performance status indicating they are fully active or restricted in physically strenuous activity but ambulatory. They should not have any conditions that would exclude them from the study.

Inclusion Criteria

I have given my written consent to participate.

My organs are functioning well.

I have had CD19 therapy before and a biopsy confirmed CD19 is still present.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of UB-VV111, with some receiving additional treatment with rapamycin

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Treatment Details

Interventions

• Rapamycin
• UB-VV111

Trial Overview The trial is testing UB-VV111 alone and combined with rapamycin to assess safety and effectiveness against certain blood cancers. It's an early-phase study where doses will gradually increase to find the safest dose that can still work.

Participant Groups

Group I: UB-VV111 + rapamycin Experimental Treatment 2 Interventions

A single dose of UB-VV111 will be administered followed by treatment with rapamycin.

Group II: UB-VV111 Experimental Treatment 1 Intervention

A single dose of UB-VV111 will be administered.

UB-VV111 is already approved in United States for the following indications:

Approved in United States as UB-VV111 for:

Who Is Running the Clinical Trial?

Umoja Biopharma

Lead Sponsor

Trials

1

Recruited

110+

Findings from Research

ABT-263, a potent inhibitor of antiapoptotic proteins, significantly enhances the effectiveness of rapamycin in treating follicular lymphoma cell lines, leading to increased cell death and apoptosis.

In xenograft models, the combination of ABT-263 and rapamycin resulted in a remarkable 100% overall response rate, indicating that this combination therapy could be a promising strategy for lymphoma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ABT-263 and rapamycin act cooperatively to kill lymphoma cells in vitro and in vivo. Ackler, S., Xiao, Y., Mitten, MJ., et al.[2020]

TORKi (second-generation mTOR kinase inhibitors) induce apoptosis in cancer cells primarily by disrupting mTOR complex 1-mediated activation of 4EBP, highlighting a specific mechanism of action that enhances their effectiveness compared to traditional treatments.

The study suggests that combining TORKi with pro-apoptotic drugs, particularly BCL-2 inhibitors, can improve treatment outcomes for aggressive B-cell lymphomas, indicating a potential strategy for optimizing therapy in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of 4EBP phosphorylation mediates the cytotoxic effect of mechanistic target of rapamycin kinase inhibitors in aggressive B-cell lymphomas. Bi, C., Zhang, X., Lu, T., et al.[2021]

In a study using a mouse model of childhood B-cell progenitor acute lymphoblastic leukemia (ALL), the mTOR inhibitor RAD001 (Everolimus) significantly increased median survival from 21.3 days to 42.3 days, indicating its potential as a more effective treatment option.

When combined with vincristine, RAD001 further enhanced survival compared to either drug alone, suggesting that this combination could be a promising strategy for improving outcomes in children with ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potentiating effects of RAD001 (Everolimus) on vincristine therapy in childhood acute lymphoblastic leukemia. Crazzolara, R., Cisterne, A., Thien, M., et al.[2022]

Buparlisib (BKM120), a pan-class I phosphatidylinositol 3-kinase inhibitor, demonstrated some efficacy in treating relapsed or refractory non-Hodgkin lymphoma, with overall response rates of 11.5% for diffuse large B-cell lymphoma, 22.7% for mantle cell lymphoma, and 25.0% for follicular lymphoma among 72 patients studied.

The treatment was associated with manageable safety concerns, with common adverse events including hyperglycemia, fatigue, and nausea, suggesting that buparlisib has an acceptable toxicity profile for further development in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pan-phosphatidylinositol 3-kinase inhibition with buparlisib in patients with relapsed or refractory non-Hodgkin lymphoma. Younes, A., Salles, G., Martinelli, G., et al.[2019]

Intravascular large B-cell lymphoma (IVLBCL) shows a significant upregulation of the mTOR complex 2 pathway, indicating that this pathway may contribute to the development of the disease.

Given the activation of the mTOR pathway in IVLBCL, mTORC2 inhibitors could be a promising treatment option for patients with this aggressive lymphoma, especially those who have relapsed or are refractory to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravascular large B-cell lymphoma: report of three cases and analysis of the mTOR pathway. Shen, Q., Duan, X., Feng, W., et al.[2021]

The study evaluated the effects of the mTOR inhibitor everolimus and the RAS/RAF pathway inhibitor L744,832 on two aggressive Non-Hodgkin Lymphoma cell lines, showing that both drugs can induce cell death primarily through apoptosis.

Combining everolimus and L744,832 enhanced their antiproliferative and cytotoxic effects, suggesting that this combination therapy could offer therapeutic benefits for patients with Diffuse Large B-cell Lymphoma and Burkitt's Lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

L744,832 and Everolimus Induce Cytotoxic and Cytostatic Effects in Non-Hodgkin Lymphoma Cells. Mendes, J., Gonçalves, AC., Alves, R., et al.[2018]

PQR620, a new dual TORC1/2 inhibitor, demonstrated significant anti-tumor activity in 56 lymphoma cell lines, with a median IC50 value of 250 nM after 72 hours, indicating its potential effectiveness against lymphoma.

When combined with the BCL2 inhibitor venetoclax, PQR620 showed increased cytotoxicity, suggesting that this combination therapy could enhance treatment outcomes for lymphoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Novel TORC1/2 Kinase Inhibitor PQR620 Has Anti-Tumor Activity in Lymphomas as a Single Agent and in Combination with Venetoclax. Tarantelli, C., Gaudio, E., Hillmann, P., et al.[2023]

References

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

ABT-263 and rapamycin act cooperatively to kill lymphoma cells in vitro and in vivo. [2020]

2. Italy pubmed.ncbi.nlm.nih.gov

Inhibition of 4EBP phosphorylation mediates the cytotoxic effect of mechanistic target of rapamycin kinase inhibitors in aggressive B-cell lymphomas. [2021]

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

Potentiating effects of RAD001 (Everolimus) on vincristine therapy in childhood acute lymphoblastic leukemia. [2022]

4. Italy pubmed.ncbi.nlm.nih.gov

Pan-phosphatidylinositol 3-kinase inhibition with buparlisib in patients with relapsed or refractory non-Hodgkin lymphoma. [2019]

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

Intravascular large B-cell lymphoma: report of three cases and analysis of the mTOR pathway. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

L744,832 and Everolimus Induce Cytotoxic and Cytostatic Effects in Non-Hodgkin Lymphoma Cells. [2018]

7. Switzerland pubmed.ncbi.nlm.nih.gov

The Novel TORC1/2 Kinase Inhibitor PQR620 Has Anti-Tumor Activity in Lymphomas as a Single Agent and in Combination with Venetoclax. [2023]