VIP152 + Venetoclax + Prednisone for Blood Cancers

Overseen By NCI Medical Oncology Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Strong CYP3A inhibitors, Strong CYP3A inducers

Disqualifiers: HIV, Active infections, Heart failure, others

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

Compensation: Varies

Number of Visits: 3

Duration: Up to 72 weeks (24 cycles)

8 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: Non-Hodgkin lymphomas are blood cancers that can be difficult to treat. They can also return after treatment. Examples include diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma (PTCL). More effective treatments are needed for these diseases. Objective: To test the safety of a study drug (Enitociclib (VIP152) in combination with other drugs used to treat people with aggressive blood cancers. Eligibility: People aged 18 years or older diagnosed with DLBCL, PTCL, or related blood cancers. The cancers must have either not responded to treatment or returned after treatment. Design: Participants will undergo screening. They will have a physical exam with scans and blood and urine tests. They will have imaging scans and tests of their heart function. They may also provide a bone marrow aspiration or biopsy. Participants may provide a saliva sample for deoxyribonucleic acid (DNA) testing. Participants will receive study treatment in cycles. Each cycle is 21 days. Participants will take two drugs by mouth at home once a day on days 1-10 of each cycle. On days 2 and 9 they will come to the clinic to receive VIP152. This drug will be administered through a small plastic tube with a needle placed in a vein. On day 11, participants will receive a fourth medication as an injection under the skin. They will rest and recover on days 12-21. Screening tests will be repeated periodically throughout the study period. Treatment will continue for up to 24 cycles. Participants will have follow-up visits for up to 5 years.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does exclude participants who are taking certain strong or moderate CYP3A inhibitors or inducers within 14 days before starting the study drugs. 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 the drug combination VIP152, Venetoclax, and Prednisone for blood cancers?

The research does not provide direct evidence for the effectiveness of the combination of VIP152, Venetoclax, and Prednisone for blood cancers. However, it mentions that prednisone is often used in combination with other drugs for prostate cancer, suggesting it may help enhance the effectiveness of cancer treatments. ^{1 2 3 4 5}

Is the combination of VIP152, Venetoclax, and Prednisone generally safe for humans?

Prednisone, when used in combination with other drugs like abiraterone acetate, has been associated with some adverse events such as fluid retention, high blood pressure, and low potassium levels. However, it generally has an acceptable safety profile in clinical settings. No specific safety data for the combination of VIP152, Venetoclax, and Prednisone was found in the provided research articles. ^{2 6 7 8 9}

What makes the drug combination of VIP152, Venetoclax, and Prednisone unique for blood cancers?

This drug combination is unique because Venetoclax is a potent oral drug that targets and inhibits a protein called BCL-2, which helps cancer cells survive. By combining it with VIP152 and Prednisone, the treatment may enhance the ability to kill cancer cells in blood cancers, offering a novel approach compared to traditional chemotherapy. ^{10 11 12 13 14}

Research Team

Christopher J Melani, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults diagnosed with aggressive blood cancers like DLBCL or PTCL, which have not responded to treatment or returned after treatment. Participants must be over 18, understand the study and consent to it, agree to use effective contraception if of childbearing potential, and cannot be breastfeeding. They should have adequate organ function and no active infections or other cancer treatments within specific time frames before the trial.

Inclusion Criteria

Ability to understand and sign a written informed consent document

Agreement to use highly effective contraception for women and men of reproductive potential

Breastfeeding participants must discontinue breastfeeding during study treatment

Exclusion Criteria

Active receipt of other anti-cancer investigational agents

HIV-positive participants

I do not have another active cancer that could interfere with treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive VIP152, venetoclax, and prednisone in 21-day cycles, with clinic visits on days 2 and 9 for VIP152 administration and day 11 for an injection

Up to 72 weeks (24 cycles)

2 visits (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Periodic visits (in-person)

Treatment Details

Interventions

• Prednisone
• Venetoclax
• VIP152

Trial Overview The trial is testing VIP152 in combination with venetoclax and prednisone (VVIP) for safety and effectiveness against relapsed/refractory lymphoid malignancies. Patients will take medications orally at home and receive VIP152 intravenously at a clinic during 21-day cycles for up to 24 cycles, followed by up to five years of follow-up visits.

Participant Groups

Group I: Cohort 2/Phase 2: Arm 2 Dose Expansion Experimental Treatment 10 Interventions

Enitociclib (VIP152), Venetoclax and prednisone (VVIP) - VIP152 and venetoclax at the recommended phase II dose (RP2D) with prednisone at fixed doses.

Group II: Cohort 1/Phase 1: Arm 1 Dose Escalation Experimental Treatment 10 Interventions

Enitociclib (VIP152), Venetoclax and prednisone (VVIP) - VIP152 and venetoclax at escalating doses with prednisone at fixed doses to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of VIP152 and venetoclax.

Prednisone is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Prednisone for:

• Allergic reactions
• Asthma
• Blood disorders
• Cancer
• Eye problems
• Immune system disorders
• Inflammatory conditions
• Multiple sclerosis
• Organ transplantation
• Rheumatoid arthritis
• Skin conditions

Approved in European Union as Prednisone for:

• Allergic reactions
• Asthma
• Blood disorders
• Cancer
• Eye problems
• Immune system disorders
• Inflammatory conditions
• Multiple sclerosis
• Organ transplantation
• Rheumatoid arthritis
• Skin conditions

Approved in Canada as Prednisone for:

• Allergic reactions
• Asthma
• Blood disorders
• Cancer
• Eye problems
• Immune system disorders
• Inflammatory conditions
• Multiple sclerosis
• Organ transplantation
• Rheumatoid arthritis
• Skin conditions

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Cabazitaxel, when combined with prednisone, significantly improves overall survival in patients with hormone-refractory metastatic prostate cancer who have previously been treated with docetaxel, as shown in the pivotal TROPIC trial.

The treatment also enhances progression-free survival and response rates for tumor and PSA levels, while maintaining an acceptable safety profile, with common side effects including hematological issues and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabazitaxel: a guide to its use in hormone-refractory metastatic prostate cancer. Keating, GM.[2021]

Switching from prednisone to dexamethasone in patients with metastatic castration-resistant prostate cancer who have progressed on abiraterone acetate plus prednisone may be beneficial, as suggested by the review of four clinical studies.

Potential candidates for this steroid switch include patients with PSA progression but no clinical or radiological progression, those without severe side effects from CYP-17 inhibition, and individuals unfit for chemotherapy or radium-223.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corticosteroid switch after progression on abiraterone acetate plus prednisone. Roviello, G., Sobhani, N., Corona, SP., et al.[2020]

Venetoclax is a highly effective treatment for relapsed or refractory chronic lymphocytic leukemia (CLL), achieving response rates of about 80% in clinical trials involving 240 patients from 2011 to 2016.

While venetoclax has an acceptable safety profile, common side effects include neutropenia and diarrhea, and there is a risk of tumor lysis syndrome (TLS), which can be managed through careful dose ramp-up and patient education, leading to no reported TLS events in ongoing trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . Brumbaugh Paradis, H., Alter, D., Llerandi, D.[2018]

In a study comparing treatment regimens for relapsed/refractory acute myeloid leukemia (R/R AML), the venetoclax (VEN) combination therapy showed a comparable overall response rate (59.3%) to intensive chemotherapy (IC) (44.0%), suggesting it is an effective alternative for patients who have failed previous treatments.

Patients receiving the VEN combination had a significantly higher percentage of successful stem cell transplants at blast clearance (86.5% vs. 62.3% for IC), indicating better disease control and potentially lower treatment-related mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective comparison of salvage intensive chemotherapy versus venetoclax-combined regimen in patients with relapsed/refractory acute myeloid leukemia (AML). Park, S., Kwag, D., Kim, TY., et al.[2022]

In a phase I study involving 48 patients with relapsed or refractory multiple myeloma (RRMM), the combination of venetoclax with daratumumab and dexamethasone (VenDd) showed a remarkable overall response rate of 96%, indicating its strong efficacy, especially in patients with the t(11;14) translocation.

The combination of venetoclax with bortezomib, daratumumab, and dexamethasone (VenDVd) also demonstrated significant efficacy, with a 92% overall response rate, and an 18-month progression-free survival rate of 66.7%, suggesting that these combinations could provide durable responses in RRMM treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Venetoclax Plus Daratumumab and Dexamethasone, With or Without Bortezomib, in Patients With Relapsed or Refractory Multiple Myeloma With and Without t(11;14). Bahlis, NJ., Baz, R., Harrison, SJ., et al.[2022]

In a study involving 272 patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), higher concentrations of venetoclax led to a quicker reduction in lymphocyte counts and tumor size, resulting in a high objective response rate (ORR) of 84.8% at a daily dose of 400 mg.

Importantly, increasing the dose of venetoclax did not correlate with a higher risk of serious adverse events like neutropenia or infections, suggesting that the 400 mg daily regimen is both effective and safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Venetoclax Exposure on Clinical Efficacy and Safety in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia. Freise, KJ., Jones, AK., Eckert, D., et al.[2018]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Safety and efficacy of the MDR inhibitor Incel (biricodar, VX-710) in combination with mitoxantrone and prednisone in hormone-refractory prostate cancer. [2018]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Cabazitaxel: a guide to its use in hormone-refractory metastatic prostate cancer. [2021]

3. Australia pubmed.ncbi.nlm.nih.gov

The Influence of Prednisone on the Efficacy of Cabazitaxel in Men with Metastatic Castration-Resistant Prostate Cancer. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Safety of cabazitaxel in senior adults with metastatic castration-resistant prostate cancer: results of the European compassionate-use programme. [2022]

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

Safety and efficacy of the multidrug resistance inhibitor Incel (biricodar; VX-710) in combination with paclitaxel for advanced breast cancer refractory to paclitaxel. [2019]

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

Abiraterone acetate and prednisone in the pre- and post-docetaxel setting for metastatic castration-resistant prostate cancer: a mono-institutional experience focused on cardiovascular events and their impact on clinical outcomes. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Phase Ib trial of reformulated niclosamide with abiraterone/prednisone in men with castration-resistant prostate cancer. [2022]

8. Japan pubmed.ncbi.nlm.nih.gov

Corticosteroid switch after progression on abiraterone acetate plus prednisone. [2020]

9. Italy pubmed.ncbi.nlm.nih.gov

[Abiraterone acetate: a novel therapeutic option in hormone-refractory prostate cancer]. [2016]

10. Cyprus pubmed.ncbi.nlm.nih.gov

Combination of Venetoclax and hypomethylating agents in relapsed/refractory acute myeloid leukemia: A case series from a single center. [2022]

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

Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . [2018]

12. England pubmed.ncbi.nlm.nih.gov

A retrospective comparison of salvage intensive chemotherapy versus venetoclax-combined regimen in patients with relapsed/refractory acute myeloid leukemia (AML). [2022]

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

Phase I Study of Venetoclax Plus Daratumumab and Dexamethasone, With or Without Bortezomib, in Patients With Relapsed or Refractory Multiple Myeloma With and Without t(11;14). [2022]

14. Switzerland pubmed.ncbi.nlm.nih.gov

Impact of Venetoclax Exposure on Clinical Efficacy and Safety in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia. [2018]