Venetoclax + CLAG-M for AML

Recruiting at 1 trial location

Overseen By Mohamad Abou Khalil

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Investigational agents

Disqualifiers: Venetoclax refractory, CNS involvement, 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

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 18 months

52 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding venetoclax, a targeted therapy, to a treatment called CLAG-M can improve outcomes for individuals with relapsed or refractory acute myeloid leukemia (AML), a type of blood cancer. Researchers seek to establish whether this combination can more effectively clear the cancer and improve survival without events like relapse. The trial will compare two groups: one receiving CLAG-M with venetoclax and another without it. This trial may suit those whose AML has returned or not responded to treatment, particularly if they haven't received certain recent therapies. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have had AML-directed therapy within 14 days before starting the trial, except for hydroxyurea, and you should not be on immunosuppressive therapy except for low-dose prednisone.

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

Research has shown that venetoclax, when combined with CLAG-M (a type of chemotherapy), is generally safe for individuals with relapsed or hard-to-treat acute myeloid leukemia (AML). In earlier studies, patients tolerated this combination well, and the side effects were manageable. Common side effects included low blood cell counts, which are expected with these treatments. These studies help confirm the treatment's safety and demonstrate that venetoclax can effectively work with other drugs like those in CLAG-M. The goal is to improve patient outcomes by reducing cancer presence and extending the time they remain free from cancer-related issues. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the venetoclax treatment for acute myeloid leukemia (AML) because it works by targeting a specific protein called BCL-2, which helps cancer cells survive. Unlike traditional chemotherapy, venetoclax is designed to promote cancer cell death by interfering with this protein, potentially offering a more precise treatment option. Additionally, when combined with the CLAG-M regimen (a mix of cladribine, cytarabine, G-CSF, and mitoxantrone), venetoclax might enhance the effectiveness of the therapy, potentially leading to better outcomes for patients with AML. This combination could provide a powerful new approach compared to standard therapies.

What evidence suggests that this trial's treatments could be effective for AML?

This trial will compare CLAG-M chemotherapy with and without venetoclax for treating relapsed or hard-to-treat acute myeloid leukemia (AML). Research has shown that adding venetoclax to CLAG-M chemotherapy may aid in treating these cases. Previous studies found that combining venetoclax with strong chemotherapy improved outcomes for high-risk patients. Venetoclax weakens cancer cells, enhancing the effectiveness of chemotherapy. Early results suggest this combination could lead to better disease control and longer survival, offering hope for patients with challenging cases of AML. ^{1 2 3 5 6}

Who Is on the Research Team?

David Sallman, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with acute myeloid leukemia (AML) that has come back or hasn't responded to treatment. Participants should be suitable for intensive chemotherapy. Specific details about inclusion and exclusion criteria are not provided, but typically these would involve age, previous treatments, and overall health status.

Inclusion Criteria

I am HIV-positive, on treatment, and my viral load has been undetectable for 6 months.

Participants with history of HCV infection must have undetectable viral load

I have chronic hepatitis B but it's under control with medication.

Exclusion Criteria

My leukemia has spread to my brain or spinal cord.

I had a stem cell transplant from a donor within the last 3 months.

My cancer has a known TP53 mutation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CLAG-M therapy with or without venetoclax

Up to 18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Venetoclax

Trial Overview The study tests if adding a drug called Venetoclax to the CLAG-M regimen (a combination of Cladribine, Cytarabine, Mitoxantrone, G-CSF) is safe and more effective than CLAG-M alone in improving outcomes for relapsed or refractory AML patients.

How Is the Trial Designed?

Group I: CLAG-based therapy with venetoclax Experimental Treatment 2 Interventions

Study participants will receive CLAG-M (cladribine, cytarabine, G-CSF, mitoxantrone) and Venetoclax

Group II: CLAG-based therapy without venetoclax Active Control 1 Intervention

Study participants will receive CLAG-M (cladribine, cytarabine, G-CSF, mitoxantrone)

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

AbbVie

Industry Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Published Research Related to This Trial

In a study of 51 patients with relapsed or refractory acute myeloid leukemia (RR-AML), venetoclax (VEN) showed a low complete remission (CR) rate of 12.4%, indicating limited effectiveness in this heavily pretreated population.

The median overall survival (OS) for patients treated with VEN was only 104 days, with 28% of patients experiencing treatment interruptions due to toxicity, highlighting the challenges and risks associated with this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Venetoclax in Patients with Relapsed or Refractory Acute Myeloid Leukemia: The PETHEMA Registry Experience. Labrador, J., Saiz-Rodríguez, M., de Miguel, D., 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 retrospective study of 40 patients with relapsed/refractory acute myeloid leukemia (AML) treated with venetoclax, 76% of those who survived more than two cycles achieved neutrophil recovery, indicating a positive response to the treatment.

Venetoclax demonstrated safety and efficacy in advanced AML, with a median overall survival of 5.5 months for all patients and 6.5 months for those who survived beyond two months, suggesting it can be a viable option for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax is safe and efficacious in relapsed/refractory AML. Ganzel, C., Ram, R., Gural, A., et al.[2021]

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 study of 43 patients with acute myeloid leukemia (AML) treated with venetoclax and hypomethylating agents (HMAs), outpatient initiation of venetoclax was found to be safe, with only one case (2.5%) of laboratory tumor lysis syndrome (TLS) and no clinical TLS episodes reported.

The 30-day mortality rate after starting venetoclax was 0%, indicating that the outpatient ramp-up approach does not compromise patient safety in this treatment setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor lysis syndrome risk in outpatient versus inpatient administration of venetoclax and hypomethlators for acute myeloid leukemia. Pelcovits, A., Moore, J., Bakow, B., et al.[2021]

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]

Venetoclax is an effective oral medication for treating chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML), showing significant efficacy when combined with other therapies like obinutuzumab and azacitidine.

While venetoclax is associated with adverse events such as neutropenia and gastrointestinal disorders, the article emphasizes the importance of managing these side effects to ensure patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practical Management of the Venetoclax-Treated Patient in Chronic Lymphocytic Leukemia and Acute Myeloid Leukemia. Waggoner, M., Katsetos, J., Thomas, E., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04797767

Study Details | NCT04797767 | Venetoclax and CLAG-M ... This phase I/II trial finds the best dose, side effects and how well giving venetoclax in combination with cladribine, cytarabine, ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40535475/

Phase 1 trial of venetoclax with cladribine, cytarabine, G- ... Intensifying induction by combining venetoclax with a high-dose cytarabine regimen may improve outcomes for high-risk populations such as adult ...

3. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper200883.html

Paper: Phase I Trial Combining Venetoclax with Cladribine ... We report the results of a phase I study of venetoclax in combination with the high-intensity induction regimen, CLAG-M, for fit patients with ND adverse-risk ...

4. fredhutch.org fredhutch.org/en/research/clinical-trials/trial-details.fh_trial_id_13940.venetoclax-and-clag-m-for-the-treatment-of-acute-myeloid-leukemia-and-high-grade-myeloid-neoplasms.html

Venetoclax and CLAG-M for the Treatment of Acute ... This phase I trial finds the best dose and side effects of venetoclax in combination with cladribine, cytarabine, granulocyte colony-stimulating ...

5. mdpi.com mdpi.com/2077-0383/13/2/549

Venetoclax Combined with Intensive Chemotherapy We discuss the mechanisms behind resistance to chemotherapy and offer a comprehensive review on current treatments of refractory/relapsed AML.

6. aacrjournals.org aacrjournals.org/clincancerres/article/31/8/1407/754524/Cladribine-Added-to-Idarubicin-and-Cytarabine-as

Cladribine Added to Idarubicin and Cytarabine as an ... However, cladribine, cytarabine, and G-CSF with/without mitoxantrone (CLAG/CLAG-M) were successfully used in R/R AML with a CR rate of about 40% and better ...