Venetoclax + Vyxeos for Leukemia

Overseen By Site Pulblic Contact

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Children's Hospital Medical Center, Cincinnati

Must not be taking: Investigational drugs, Anti-cancer agents

Disqualifiers: APML, CNS status 3, Ph+ leukemia, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 3

Duration: 3-4 weeks

21 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining two drugs, venetoclax (a targeted therapy) and Vyxeos (a chemotherapy), is safe and tolerable for young patients with certain types of leukemia that have returned or resisted treatment. It specifically targets those with acute myeloid leukemia, myeloid sarcoma, or certain types of acute lymphoblastic leukemia. Participants should have previously tried treatments that were ineffective and must have recovered from side effects of past therapies. This study may suit patients who continue to face challenges with their leukemia despite prior treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you cannot be on other anti-cancer agents, except for certain exceptions like intrathecal agents or hydroxyurea.

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

Previous studies have shown that venetoclax and Vyxeos are generally well-tolerated. Research indicates that venetoclax, approved by the FDA for certain blood cancers, blocks a protein that helps cancer cells survive, aiding in their destruction. Vyxeos is a specialized chemotherapy that combines two drugs to target leukemia cells.

Reported side effects of venetoclax include nausea, diarrhea, and low blood cell counts, but these are usually manageable. Vyxeos can also cause low blood cell counts, and some people may experience fatigue or infections. However, these effects are common in cancer treatments and are closely monitored by doctors.

Overall, the combination of venetoclax and Vyxeos has been used before and is considered safe enough for a new combination trial. Doctors closely monitor patients to address any side effects promptly. Participants should communicate any changes in how they feel to the team for support. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for leukemia involve chemotherapy that targets rapidly dividing cells, but researchers are excited about combining Venetoclax and Vyxeos because they offer a unique approach. Venetoclax specifically targets and inhibits BCL-2, a protein that helps cancer cells survive, making it a precision treatment. Vyxeos is a liposomal formulation that delivers a fixed combination of two chemotherapy drugs directly to the leukemia cells, enhancing their effectiveness and potentially reducing side effects. This combination aims to be more effective and targeted than traditional chemotherapy, offering hope for improved outcomes.

What evidence suggests that the combination of Venetoclax and Vyxeos could be effective for acute leukemia?

Research has shown that using venetoclax with Vyxeos, the combination tested in this trial, may help treat acute leukemia. Early studies suggest these drugs work well together because they attack cancer cells in different ways. Venetoclax kills cancer cells by blocking a protein they need to survive. Vyxeos is a special type of chemotherapy that delivers two drugs directly to leukemia cells. Initial studies found that using venetoclax with similar drugs was safe and showed early signs of helping patients. This combination aims to better fight leukemia that has returned or not responded to other treatments. ^{6 7 8 9 10}

Who Is on the Research Team?

John Perentesis, MD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Are You a Good Fit for This Trial?

This trial is for young patients aged 1-39 with acute leukemia that's relapsed or hasn't responded to treatment. They should have recovered from previous therapies and not have certain other health conditions like Fanconi Anemia or Wilson's Disease, be pregnant, breastfeeding, or unable to swallow pills.

Inclusion Criteria

I am between 1 and 39 years old.

I've recovered from previous cancer treatments and it's been enough time since my last major therapy.

My leukemia has returned or didn't respond to treatment.

Exclusion Criteria

You have been diagnosed with certain types of leukemia, genetic disorders, or other medical conditions. You are pregnant or breastfeeding, have an uncontrolled infection, have received a high amount of radiation to the chest area, cannot swallow pills, have recently received certain medications or treatments, are currently taking experimental drugs or other anti-cancer medications (with a few exceptions), or are unable to follow the safety monitoring requirements of the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single course of venetoclax and Vyxeos. Venetoclax is given daily with a 3-day ramp-up, and Vyxeos is administered intravenously on Days 1, 3, and 5.

3-4 weeks

3 visits (in-person) for Vyxeos administration

Follow-up

Participants are monitored for safety, tolerability, and response to treatment, including pharmacokinetic analysis and cardiac function assessment.

60 days

What Are the Treatments Tested in This Trial?

Interventions

• Venetoclax
• Vyxeos

Trial Overview The study tests combining Venetoclax with Vyxeos (CPX-351) in pediatric and young adult patients. It aims to assess the safety of this combination therapy in those whose acute leukemia has returned or is resistant to standard treatments.

How Is the Trial Designed?

Group I: Venetoclax and Vyxeos combination Experimental Treatment 2 Interventions

Venetoclax will be given orally on Days per the assigned dose level. A single course consisting of 3 doses of Vyxeos and 7-21 doses of venetoclax depending on the assigned dose level will be administered to participants in this study. Vyxeos will be administered by central venous catheter over 90 minutes on Day 1, 3, and 5. Venetoclax is given daily by mouth per assigned dose level.

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

Approved in United States as Venclexta for:

• Chronic lymphocytic leukemia (CLL)
• Small lymphocytic lymphoma (SLL)
• Acute myeloid leukemia (AML)

Approved in European Union as Venclyxto for:

• Chronic lymphocytic leukemia (CLL)
• Small lymphocytic lymphoma (SLL)
• Acute myeloid leukemia (AML)

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

Published Research Related to This Trial

The combination of venetoclax with bendamustine-rituximab (BR) was found to be safe and tolerable in a study of 60 patients with relapsed/refractory non-Hodgkin's lymphoma, with the recommended phase II dose established at 800 mg daily.

The overall response rate to the treatment was 65%, with a median duration of response of 38.3 months, indicating preliminary efficacy for this combination therapy in managing B-cell NHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax, bendamustine, and rituximab in patients with relapsed or refractory NHL: a phase Ib dose-finding study. de Vos, S., Swinnen, LJ., Wang, D., et al.[2021]

Venetoclax is an effective oral treatment for relapsed or refractory chronic lymphocytic leukemia (CLL), showing durable responses and a manageable safety profile in clinical trials, including patients with poor prognostic factors.

In combination with rituximab, venetoclax significantly improved progression-free survival and achieved undetectable minimal residual disease compared to bendamustine plus rituximab, with benefits lasting for at least 36 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Relapsed/Refractory Chronic Lymphocytic Leukemia. Scott, LJ.[2020]

Venetoclax is an oral medication that selectively inhibits the BCL-2 protein, which helps cancer cells survive, thereby restoring the ability of these malignant cells to undergo programmed cell death (apoptosis).

It has been approved in the USA for treating chronic lymphocytic leukaemia (CLL) in patients with a specific genetic marker (17p deletion) who have already undergone at least one prior therapy, and it is being studied for various other blood cancers and conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: First Global Approval. Deeks, ED.[2018]

In a Phase 3 clinical trial, venetoclax combined with low-dose cytarabine showed improved response rates and overall survival in patients with newly diagnosed acute myeloid leukemia who couldn't undergo intensive chemotherapy, supporting its efficacy.

In an expanded access study in Japan involving 14 patients, the safety profile of venetoclax was consistent with previous findings, with neutropenia being the most common serious side effect, indicating that careful management of adverse events is crucial in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax plus low-dose cytarabine in patients with newly diagnosed acute myeloid leukemia ineligible for intensive chemotherapy: an expanded access study in Japan. Asada, N., Ando, J., Takada, S., et al.[2023]

In a study involving 15 Chinese patients with acute myeloid leukemia (AML) who could not tolerate intensive chemotherapy, venetoclax combined with low-dose cytarabine (LDAC) showed a 38% reduction in the risk of death compared to placebo, with a median overall survival of 9.0 months versus 4.1 months for the placebo group.

The treatment resulted in a complete remission rate of 33% among those receiving venetoclax, while no patients in the placebo group achieved remission, indicating that venetoclax with LDAC is an effective option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Venetoclax with low-dose cytarabine for patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy: results from the Chinese cohort of a phase three randomized placebo-controlled trial]. Hu, Y., Jin, J., Zhang, Y., et al.[2021]

In a study of 211 patients with untreated acute myeloid leukemia (AML) who were not eligible for intensive chemotherapy, venetoclax combined with low-dose cytarabine (LDAC) showed a median overall survival of 8.4 months compared to 4.1 months for the placebo group, indicating a 30% reduction in the risk of death.

The treatment with venetoclax + LDAC also resulted in significantly higher complete response rates (48.3% vs. 13.2%) and improved event-free survival (4.9 months vs. 2.1 months), while maintaining a similar safety profile to the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

6-month follow-up of VIALE-C demonstrates improved and durable efficacy in patients with untreated AML ineligible for intensive chemotherapy (141/150). Wei, AH., Panayiotidis, P., Montesinos, P., et al.[2022]

In the phase III CLL14 trial, a 12-month treatment with venetoclax combined with obinutuzumab significantly improved progression-free survival and rates of undetectable minimal residual disease compared to traditional chemoimmunotherapy with chlorambucil and obinutuzumab in patients with untreated chronic lymphocytic leukaemia.

Venetoclax + obinutuzumab is a well-tolerated, chemotherapy-free treatment option for CLL, with manageable side effects like neutropenia, making it suitable for patients who cannot undergo intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. Blair, HA.[2021]

In a subgroup of 27 Japanese patients with newly diagnosed acute myeloid leukaemia, venetoclax combined with low-dose cytarabine showed a higher complete remission rate (44.4%) compared to placebo (11.1%), indicating potential efficacy in this population.

Despite the higher remission rate, the median overall survival was similar between the venetoclax (4.7 months) and placebo (8.1 months) groups, suggesting limited survival benefit, which may be influenced by small sample size and baseline health differences among patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax plus low-dose cytarabine in Japanese patients with untreated acute myeloid leukaemia ineligible for intensive chemotherapy. Yamauchi, T., Yoshida, C., Usuki, K., et al.[2022]

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 of 82 adult patients with acute myeloid leukemia (AML), 57% were able to start venetoclax treatment safely in an outpatient setting, demonstrating its feasibility outside of the hospital.

The risk of tumor lysis syndrome (TLS) was very low, with only 2.1% of patients experiencing TLS after starting venetoclax, and 98% of patients did not require hospitalization for TLS within the first week of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outpatient initiation of venetoclax in patients with acute myeloid leukemia. Palmer, S., Patel, A., Wang, C., et al.[2023]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39418644

Lower-intensity CPX-351 plus venetoclax induction for ... Preclinical data suggest a rationale for combining CPX-351, a dual-drug liposomal encapsulation of daunorubicin and cytarabine, with venetoclax, ...

2. ashpublications.org ashpublications.org/blood/article/145/17/1870/535523/Venetoclax-plus-daunorubicin-and-cytarabine-for

Venetoclax plus daunorubicin and cytarabine for newly ... In this study, we report the initial safety and preliminary efficacy of Ven at escalating durations when combined with daunorubicin (Dauno) and ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03826992

NCT03826992 | Venetoclax Combined With Vyxeos (CPX ... This study evaluates the safety and tolerability of combining venetoclax with Vyxeos (CPX-351) in pediatric and young adult patients with acute leukemia that ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35507945/

Real-world effectiveness of CPX-351 vs venetoclax ... - PubMed CPX-351 and venetoclax and azacitidine (ven/aza) are both indicated as initial therapy for acute myeloid leukemia (AML) in older adults.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6520

V-RULES: Real-world effectiveness and safety of CPX-351 ... These results highlight the effectiveness and safety of CPX-351 for the treatment of t-AML and AML-MRC in the US RW setting, consistent with the pivotal trial ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6524989/

Venetoclax Combined With Low-Dose Cytarabine for ... An international phase Ib/II study evaluated the safety and preliminary efficacy of venetoclax, a selective B-cell leukemia/lymphoma-2 inhibitor, together with ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05554419

Study Details | NCT05554419 | Testing the Use of ... This phase II MyeloMATCH treatment trial compares cytarabine versus (vs.) cytarabine and venetoclax vs. liposome-encapsulated daunorubicin-cytarabine and ...

8. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03629171/

Clinical Trial: NCT03629171 This phase II trial studies how well liposome-encapsulated daunorubicin-cytarabine and venetoclax work in treating participants with acute ...

9. ashpublications.org ashpublications.org/bloodadvances/article/8/13/3583/516002/Venetoclax-a-new-player-in-the-treatment-of

Venetoclax: a new player in the treatment of children with high ... This review summarizes the available current knowledge about venetoclax use in childhood high-risk myeloid neoplasms and discusses the possible integration of ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6499443/

Evaluating venetoclax and its potential in treatment-naïve ... Venetoclax (ABT-199), a BH3-mimetic and selective BCL-2 inhibitor, was recently approved by the US Food and Drug Administration (FDA) for the treatment of acute ...