Venetoclax + Navitoclax for Acute Lymphoblastic Leukemia

Not currently recruiting at 1 trial location
Seth E. Karol, MD profile photo
Overseen BySeth E. Karol, MD
Age: < 65
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: St. Jude Children's Research Hospital
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment plan for children with acute lymphoblastic leukemia or lymphoma that hasn't responded to other treatments. It combines two oral drugs, venetoclax and navitoclax, with other chemotherapy medications to evaluate their effectiveness against this cancer. The study aims to determine the best dose and assess patient response to this combination. It suits children who have tried other treatments without success and can take pills. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering a chance to be among the first to receive this new combination therapy.

Do I have to stop taking my current medications for the trial?

The trial requires you to stop taking certain medications, specifically moderate or strong CYP3A inhibitors and inducers, within a few days before starting the trial. You should also avoid grapefruit, Seville oranges, and star fruit. It's best to discuss your current medications with the trial team to see if any need to be adjusted.

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

Research has shown that the combination of venetoclax and navitoclax is being tested for safety and effectiveness in treating relapsed or refractory acute lymphoblastic leukemia (rALL). In previous studies, all patients experienced some side effects, known as adverse events. For more serious side effects, classified as Grade 3 or 4, the rate was 89%. These side effects are common with many cancer treatments and are considered when doctors determine safe doses.

Despite these side effects, the treatment has demonstrated positive responses in both children and adults with rALL, reducing cancer cells in some patients. Importantly, no major issues arose with how the drugs interacted in the body, allowing venetoclax and navitoclax to be used safely together.

Overall, while side effects exist, this treatment is considered manageable, meaning most patients can handle them with medical support. The goal is to balance side effects with the potential benefits of treating rALL.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Acute Lymphoblastic Leukemia (ALL) because they introduce a new approach to tackling the disease. Venetoclax and Navitoclax target and inhibit proteins like BCL-2 that help cancer cells survive, which is different from traditional chemotherapy that attacks rapidly dividing cells indiscriminately. This targeted action could potentially lead to fewer side effects and improved effectiveness against resistant cancer cells. Additionally, the combination of these drugs with other agents like Blinatumomab and Dasatinib might enhance the overall treatment outcome by addressing multiple pathways that contribute to leukemia progression. This multi-faceted approach could offer hope for patients with limited options, especially those who have relapsed.

What evidence suggests that this trial's treatments could be effective for acute lymphoblastic leukemia?

Research has shown that the combination of venetoclax and navitoclax may effectively treat acute lymphoblastic leukemia (ALL) that has returned or is not responding to treatment. In this trial, participants will receive venetoclax and navitoclax as part of different treatment blocks. Studies have found that nearly half of the patients achieved complete remission (CR), meaning no cancer cells were detected, after receiving this treatment. Specifically, 44% of patients undergoing a second round of treatment achieved complete remission. This combination targets proteins that help cancer cells survive, potentially enhancing treatment effectiveness. Early results suggest that adding these drugs to chemotherapy can restore treatment effectiveness in children. Overall, the evidence supports venetoclax and navitoclax as promising options for patients with relapsed or refractory ALL.13678

Who Is on the Research Team?

Seth Karol, MD - St. Jude Children's ...

Seth E. Karol, MD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 4 to under 30 with relapsed or refractory acute lymphoblastic leukemia/lymphoma. They must have certain levels of disease in the bone marrow or blood, be able to swallow pills, have no severe heart issues, and not have had certain recent treatments. Those with Down Syndrome are eligible only for specific parts of the study.

Inclusion Criteria

I am mostly able to do daily activities but need some help.
Specific criteria for patients with prior hematopoietic stem cell transplant
My leukemia or lymphoma has returned or didn't respond to treatment, with specific bone marrow involvement.
See 9 more

Exclusion Criteria

Pregnant or lactating
Inability or unwillingness to give written informed consent
I am currently taking certain medications or consuming specific foods.
See 1 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Block 1 Therapy

Participants receive combination chemotherapy with venetoclax and navitoclax, along with other agents, to evaluate activity in relapsed or refractory acute lymphoblastic leukemia or lymphoma.

4 weeks
Weekly visits for drug administration and monitoring

Block 2 Therapy

Participants receive either Block 2A or Block 2B therapy based on CD19 status, involving venetoclax combinations with either blinatumomab or high-dose cytarabine and navitoclax.

4-6 weeks
Frequent visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of minimal residual disease and overall survival.

1, 3, and 5 years from study entry

What Are the Treatments Tested in This Trial?

Interventions

  • Venetoclax and Navitoclax
Trial Overview The trial tests a combination chemotherapy using venetoclax and navitoclax on patients with relapsed leukemia/lymphoma. It aims to find the best dose when combined with either blinatumomab (for CD19-positive patients) or high-dose cytarabine (for CD19-negative patients), comparing results against past data.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Group I: Block 2Experimental Treatment17 Interventions
Group II: Block 1Experimental Treatment10 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials
451
Recruited
5,326,000+

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 profile image

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Citations

NCT03181126 | A Study of Venetoclax in Combination ...This dose-escalating study is to determine the safety, pharmacokinetics, and preliminary efficacy of venetoclax in combination with navitoclax and ...
Early-Phase Study Shows Promising Response Rates With ...Nearly half of patients with relapsed/refractory acute lymphocytic leukemia (ALL) had a complete response (CR) after treatment with a ...
Venetoclax and Navitoclax in Combination with ...Complete remission (CR) rates as low as 44% and 18% have been reported with second salvage for pediatric and adult patients with relapsed/refractory ALL, ...
Combination BCL-2 Inhibitor Therapy with Venetoclax and ...We report updated outcomes for 24 pts with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LLy) treated with venetoclax+navitoclax and ...
Rescuing of the Chemotherapy Sensitivity in Relapsed ...We retrospectively collected safety and efficacy data of VEN/NAV combined with chemotherapy in pediatric patients and young adults with r/r ALL ...
Safety and Efficacy of Venetoclax in Combination with ...Twenty-five percent of pts went on to SCT or CAR-T after achieving good response. There was no significant pharmacokinetic interaction between ...
Safety and Efficacy of Venetoclax in Combination with ...Safety and efficacy of Venetoclax in combination with Navitoclax in adult and pediatric relapsed/refractory acute lymphoblastic leukemia and lymphoblastic ...
Phase I results show venetoclax and navitoclax ...All patients experienced adverse events (AEs) of any grade, and the rate of Grade 3/4 AEs was 89%. Grade 3/4 AEs related to venetoclax or ...
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