Accelerated Venetoclax Escalation for Chronic Lymphocytic Leukemia

(SAVE Trial)

JC
MF
CC
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Overseen ByCeleste Carey, MS
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: Dana-Farber Cancer Institute
Must be taking: Venetoclax
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
Approved in 2 JurisdictionsThis treatment is already approved in other countries

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a faster method to increase doses of venetoclax, a medication for certain cancers, in individuals with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The researchers aim to determine if patients can safely manage a quicker dose escalation over five days instead of the usual five weeks. Participants may also receive additional treatments like rituximab or obinutuzumab. Individuals with a confirmed diagnosis of CLL or SLL, experiencing symptoms that affect daily life, such as significant fatigue or spleen swelling, may be suitable for this trial. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to contribute to groundbreaking cancer research.

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

The trial protocol does not specify if you must stop all current medications. However, you cannot take medications or foods that are strong inhibitors or inducers of CYP3A starting 1 week before the first dose of venetoclax. If you're on targeted therapies, a washout period of at least five half-lives is required. Corticosteroid therapy (prednisone or equivalent ≤20 mg daily) is allowed.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications or foods that strongly affect CYP3A enzymes at least one week before starting venetoclax. If you're on targeted therapies, a washout period (time without taking certain medications) of at least five half-lives is needed, unless otherwise approved by the study investigator.

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

Research has shown that venetoclax is generally well-tolerated by patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Studies have identified some common side effects, such as low blood cell counts, diarrhea, and nausea, which were mostly mild to moderate.

When combined with other treatments like obinutuzumab or rituximab, venetoclax maintains a similar safety profile. Patients might experience the same side effects, but these are usually manageable with proper care.

The FDA has already approved venetoclax for use in CLL, indicating a strong safety record when used as directed. Ongoing research is exploring a faster way to increase the dose, so safety data is still being collected. However, past findings provide a hopeful indication of its safety.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about accelerated venetoclax escalation for chronic lymphocytic leukemia (CLL) because it aims to rapidly increase the dosage of venetoclax, potentially achieving full therapeutic effects much faster than traditional methods. Unlike standard CLL treatments, which usually require gradual dosage increases over several weeks to minimize the risk of tumor lysis syndrome (TLS), this approach seeks to safely escalate the dose over just five days. Additionally, venetoclax itself is a BCL-2 inhibitor, which works differently from many traditional CLL treatments by directly inducing cancer cell death. This accelerated approach could significantly reduce the time patients spend in the hospital and allow for quicker transitions to at-home care, potentially improving quality of life and treatment outcomes.

What evidence suggests that this trial's treatments could be effective for chronic lymphocytic leukemia?

Research has shown that venetoclax, the primary treatment in this trial, effectively treats chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Studies have found that venetoclax targets a protein called BCL2, which helps cancer cells survive. By blocking BCL2, venetoclax helps kill these cancer cells. In one study, 77% of patients with CLL that had returned or didn't respond to other treatments experienced a positive response to venetoclax. This drug has proven effective even in patients with high-risk genetic changes, such as a specific type of CLL called del(17p). Overall, venetoclax has a strong track record of helping patients with these blood cancers. Participants in this trial may also receive rituximab or obinutuzumab alongside venetoclax, as determined by their doctor.45678

Who Is on the Research Team?

Jennifer Crombie, MD - Dana-Farber ...

Jennifer Crombie, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed or relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Participants must have symptoms like anemia, weight loss, fatigue, fevers without infection, night sweats, and adequate organ function. They should not have had a recent stem cell transplant or other cancers and must be willing to use contraception.

Inclusion Criteria

My white blood cell count has rapidly increased recently.
My blood tests show worsening anemia or low platelets.
I have had significant weight loss, fatigue, fevers, or night sweats without infection.
See 15 more

Exclusion Criteria

My cancer has spread to my brain or spinal cord.
I had a stem cell transplant less than 6 months ago or I am being treated for graft vs. host disease.
I am taking Coumadin or another blood thinner.
See 17 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive venetoclax with accelerated dose increases over 5 days, followed by daily administration at home. Some may also receive rituximab or obinutuzumab.

5 days for dose ramp-up, followed by up to 6 cycles of additional treatment
Hospitalized for 5 days, then regular follow-ups

Active Follow-up

Participants are actively followed for approximately 3 months to monitor safety and effectiveness.

3 months

Long-term Follow-up

Participants enter a long-term follow-up period where they will be observed for a maximum of 5 years.

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

  • Obinutuzumab
  • Rituximab
  • Venetoclax
Trial Overview The study tests if patients can safely handle a faster dose increase of Venetoclax compared to the standard schedule. It's for those at different risks for tumor lysis syndrome. Some may also receive Rituximab or Obinutuzumab as part of their treatment regimen.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: VenetoclaxExperimental Treatment3 Interventions

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

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Approved in United States as Venclexta for:
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Approved in European Union as Venclyxto for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials
1,128
Recruited
382,000+

Published Research Related to This Trial

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.
Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia.Blair, HA.[2021]
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.
Venetoclax: First Global Approval.Deeks, ED.[2018]
Venetoclax, a BCL-2 antagonist, is effective in treating chronic lymphocytic leukemia (CLL) and acute myelogenous leukemia (AML), but many patients eventually develop resistance to the treatment.
Understanding the mechanisms of resistance to venetoclax is crucial for developing new combination therapies, which are currently being tested in clinical trials to enhance treatment efficacy.
The path to venetoclax resistance is paved with mutations, metabolism, and more.Sullivan, GP., Flanagan, L., Rodrigues, DA., et al.[2023]

Citations

NCT01889186 | A Study of the Efficacy of ABT-199 in ...This was an open-label, multicenter, global study to determine the efficacy of ABT-199 ( Venetoclax ) monotherapy in participants with relapsed/refractory (R/R) ...
The potential of venetoclax (ABT-199) in chronic lymphocytic ...This review summarizes the role of BCL2 in CLL pathogenesis, the development path targeting its inhibition prior to VEN, and the preclinical and clinical data ...
Venetoclax (ABT-199/GDC-0199) Monotherapy Induces ...A phase 1 study of VEN showed high response rates in pts with relapsed/refractory (R/R) CLL, including del(17p) CLL (overall response rate, ORR = 77%). This ...
Targeting BCL2 with Venetoclax in Relapsed Chronic ...Selective targeting of BCL2 with venetoclax had a manageable safety profile and induced substantial responses in patients with relapsed CLL or SLL.
A Phase 2 Open-Label Study of the Efficacy and Safety ...This was an open-label, non-randomized, multicenter, Phase 2 study evaluating the efficacy and safety of ABT-199 in 127 participants with relapsed or refractory ...
VEN+G Safety Data for CLL/SLL - venclextaLearn about the VEN+G safety profiles for the VENCLEXTA® CLL regimens, including common adverse reactions. See full safety and Prescribing Information for ...
Safety and Efficacy of a Combination of Venetoclax (GDC ...We present preliminary efficacy and updated safety data from an ongoing phase 1b study (NCT01685892) evaluating this combination in R/R or treatment-naïve (TN) ...
VEN+R Safety Data for CLL/SLL - venclextaVENCLEXTA-based regimens offer well-studied safety profiles with exposure limited to 2 years1* · No ongoing treatment exposure · VEN+R safety from the MURANO ...
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