UB-VV111 + Rapamycin for B-Cell Lymphoma

Recruiting at 9 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of a new treatment called UB-VV111 for certain blood cancers, specifically relapsed or hard-to-treat large B-cell lymphoma (LBCL) and chronic lymphocytic leukemia (CLL). Researchers aim to assess how well this treatment works alone and in combination with another drug, rapamycin, an immunosuppressant. This study may suit individuals who have tried other treatments for LBCL or CLL without success. Participants must have a confirmed diagnosis of these cancers and no serious infections or uncontrolled health issues. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

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

Researchers are currently studying UB-VV111 to determine its safety for treating certain B-cell cancers. Since the study is in its early stages, specific safety information is not yet available. Researchers are determining the right dose and monitoring for any side effects in participants.

The study also examines UB-VV111 in combination with rapamycin, a drug used in other treatments, to assess safety and efficacy. In this early trial phase, researchers exercise caution to ensure safety. This phase typically involves small patient groups to closely monitor side effects and patient tolerance.

While specific safety data is not yet available, the early trial phase focuses on ensuring the treatment's safety for further testing. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for B-cell lymphoma, which often involve chemotherapy and targeted agents like rituximab, UB-VV111 offers a novel approach. UB-VV111 is unique because it introduces a new active ingredient that targets cancer cells in a potentially more precise manner. Researchers are excited about the combination of UB-VV111 with rapamycin because it may enhance the effectiveness of the treatment by inhibiting pathways that help cancer cells grow. This dual approach could lead to better outcomes for patients compared to existing therapies.

What evidence suggests that this trial's treatments could be effective for B-cell lymphoma?

Research is investigating UB-VV111 as a potential treatment for certain B-cell lymphomas, such as relapsed/refractory large B-cell lymphoma (LBCL) and chronic lymphocytic leukemia (CLL). The FDA has granted UB-VV111 a Fast Track designation, indicating that early results are promising enough to expedite its development. In this trial, some participants will receive UB-VV111 alone, while others will receive it combined with rapamycin. Researchers are examining how UB-VV111 interacts with rapamycin, a drug known to inhibit the growth of lymphoma cells. Although data on UB-VV111's effectiveness remains limited due to its early research stage, adding rapamycin could enhance its efficacy. These treatments are under close observation for their potential to address these challenging conditions. ^{1 2 3 4 5}

Who Is on the Research Team?

Jacob Garcia, MD

Principal Investigator

Umoja Biopharma

Are You a Good Fit for This Trial?

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

I have given my written consent to participate.

My organs are functioning well.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS2681

A phase I, multicenter, open-label study of UB-VV111 in ... A phase I, multicenter, open-label study of UB-VV111 in combination with rapamycin in relapsed/refractory CD19+ B-cell malignancies. Author: ...

2. onclive.com onclive.com/view/fda-grants-fast-track-designation-to-ub-vv111-for-r-r-b-cell-malignancies

FDA Grants Fast Track Designation to UB-VV111 for R/R B- ... An ongoing phase 1 trial (NCT06528301) is investigating the safety and efficacy of UB-VV111 in patients with CD19-positive B-cell malignancies.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06528301

NCT06528301 | A Phase 1 Study of UB-VV111 With and ... 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 ...

4. lymphomahub.com lymphomahub.com/medical-information/ub-vv111-granted-fda-fast-track-designation-for-the-treatment-of-rr-lbcl-and-cll

UB-VV111 granted FDA fast track designation for the ... An ongoing phase I trial (NCT06528301) is assessing the safety and efficacy of UB-VV111 in patients with R/R CD19+ LBCL or CLL.1. UB-VV111 was ...

5. cancernetwork.com cancernetwork.com/view/fda-grants-fast-track-designation-to-ub-vv111-in-select-b-cell-malignancies

FDA Grants Fast Track Designation to UB-VV111 in Select ... A phase 1 trial is evaluating UB-VV111 with and without rapamycin as treatment for patients with CLL and LBCL who received at least 2 prior ...