Acalabrutinib + Obinutuzumab + Chlorambucil for Chronic Lymphocytic Leukemia

(ElevateTN Trial)

Not currently recruiting at 294 trial locations
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial
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 different drug combinations to determine the most effective treatment for chronic lymphocytic leukemia (CLL), a type of blood cancer. Researchers compare three treatments: one with obinutuzumab (Gazyva) and chlorambucil, another with acalabrutinib (Calquence) and obinutuzumab, and a third with only acalabrutinib. The trial seeks participants who have not received prior treatment and have active CLL impacting their daily life, such as fatigue or unintentional weight loss. Joining this study may help identify a better way to treat CLL. As a Phase 3 trial, it represents the final step before FDA approval, offering a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you require certain medications like proton-pump inhibitors or strong CYP3A inhibitors/inducers. It's best to discuss your current medications with the trial team.

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

Research shows that both acalabrutinib and obinutuzumab are generally well-tolerated by patients with chronic lymphocytic leukemia (CLL). Studies have found that acalabrutinib is safer than traditional chemoimmunotherapy, particularly regarding heart-related side effects.

When combined, acalabrutinib and obinutuzumab are safe for most patients, with side effects that are usually manageable. These can include mild issues like headaches and tiredness, while more serious side effects are less common but possible.

Chlorambucil, used in another treatment option, has a long history in cancer treatment. It can cause side effects like low blood cell counts and nausea, but these are often manageable.

Overall, previous research and real-world patient experiences have shown these treatments to be safe. However, potential participants should discuss any concerns with their healthcare provider.12345

Why are researchers excited about this trial's treatments?

Most treatments for Chronic Lymphocytic Leukemia (CLL), like ibrutinib or rituximab, work by targeting specific proteins on cancer cells to stop their growth. But acalabrutinib, included in this study, works differently by more selectively inhibiting the Bruton's tyrosine kinase (BTK) enzyme, potentially leading to fewer side effects and better patient tolerance. The combination of obinutuzumab, a monoclonal antibody, with chlorambucil or acalabrutinib provides a potent approach to attacking cancer cells from multiple angles, aiming to enhance efficacy. Researchers are excited about these treatments because they offer new hope for improved patient outcomes and quality of life by possibly reducing toxicity and increasing effectiveness against CLL.

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

Research has shown that acalabrutinib, one of the treatments in this trial, is very effective in treating chronic lymphocytic leukemia (CLL) when used alone. In one study, 92% of patients who received acalabrutinib and immunotherapy experienced no cancer growth, compared to 47% of those who received traditional treatments. In this trial, some participants will receive acalabrutinib alone, while others will receive it in combination with obinutuzumab. The combination of acalabrutinib with obinutuzumab has also shown promise. Specifically, this combination improved survival rates and was more effective in preventing cancer progression than acalabrutinib alone. A study found that this combination had an 87% rate of patients living without cancer progression for 48 months. These findings suggest that both acalabrutinib alone and in combination with obinutuzumab could be effective options for treating CLL.12678

Who Is on the Research Team?

AC

AstraZeneca Clinical Study Information Center

Principal Investigator

1-877-240-9479 information.center@astrazeneca.com

Are You a Good Fit for This Trial?

This trial is for adults with untreated chronic lymphocytic leukemia (CLL). Participants must be over 18, have a certain level of kidney function, and not have had previous systemic treatments for CLL. They should also meet specific health criteria like a particular white blood cell count and organ function. Women who can become pregnant and men who can father children must use effective contraception.

Inclusion Criteria

I am a man who can father children and agree to use effective birth control.
I am either over 65 years old or between 18 and 65 with specific conditions.
I have been diagnosed with CLL that tests positive for CD20.
See 7 more

Exclusion Criteria

Concurrent participation in another therapeutic clinical trial
I am currently taking warfarin or a similar blood thinner.
I have been diagnosed with prolymphocytic leukemia or Richter's syndrome.
See 20 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive treatment with Acalabrutinib and Obinutuzumab, Acalabrutinib monotherapy, or Obinutuzumab and Chlorambucil over 6 cycles

6 cycles

Maintenance

Participants continue on study to generate more evidence, with more than 430 subjects currently in this phase

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 40 months

What Are the Treatments Tested in This Trial?

Interventions

  • Acalabrutinib
  • Chlorambucil
  • Obinutuzumab
Trial Overview The study compares the effectiveness of two treatment combinations: obinutuzumab with chlorambucil versus acalabrutinib with obinutuzumab, as well as acalabrutinib alone in treating CLL. It looks at how long patients live without their disease getting worse, overall response rate to treatment, time until next treatment is needed, and overall survival rates.
How Is the Trial Designed?
3Treatment groups
Experimental Treatment
Active Control
Group I: Arm C - Acalabrutinib MonotherapyExperimental Treatment1 Intervention
Group II: Arm B - Acalabrutinib in Combination with ObinutuzumabExperimental Treatment2 Interventions
Group III: Arm A - Obinutuzumab in Combination with ChlorambucilActive Control2 Interventions

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

🇺🇸
Approved in United States as Calquence for:
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Approved in European Union as Calquence for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

Acerta Pharma BV

Lead Sponsor

Trials
46
Recruited
5,900+

Published Research Related to This Trial

Acalabrutinib, a selective Bruton tyrosine kinase inhibitor, showed improved safety outcomes compared to other targeted therapies for treatment-naïve chronic lymphocytic leukemia (CLL) patients, although it was associated with a higher risk of neutropenia and leukopenia in some cases.
The analysis indicated that acalabrutinib (with or without obinutuzumab) had similar efficacy in terms of progression-free survival compared to other treatments, suggesting it is a safe and effective option for CLL patients.
Matching-adjusted indirect comparisons of safety and efficacy of acalabrutinib versus other targeted therapies in patients with treatment-naïve chronic lymphocytic leukemia.Davids, MS., Telford, C., Abhyankar, S., et al.[2021]
In a phase 3 study involving 535 patients with treatment-naive chronic lymphocytic leukaemia, acalabrutinib combined with obinutuzumab or as a monotherapy significantly improved progression-free survival compared to the standard treatment of obinutuzumab with chlorambucil, with median survival not reached for the acalabrutinib groups versus 22.6 months for the chlorambucil group.
The safety profile of acalabrutinib was favorable, with fewer infusion reactions and a lower incidence of grade 3 or higher adverse events compared to the obinutuzumab-chlorambucil group, indicating it is a viable chemotherapy-free treatment option for patients.
Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial.Sharman, JP., Egyed, M., Jurczak, W., et al.[2021]
Obinutuzumab, in combination with chlorambucil, significantly improved progression-free survival (PFS) in patients with previously untreated chronic lymphocytic leukemia (CLL), with a median PFS of 23.0 months compared to 11.1 months for chlorambucil alone.
The treatment also resulted in a higher overall response rate (ORR) of 75.9% for the obinutuzumab group versus 32.1% for the chlorambucil group, indicating its efficacy in treating CLL.
U.S. Food and drug administration approval: obinutuzumab in combination with chlorambucil for the treatment of previously untreated chronic lymphocytic leukemia.Lee, HZ., Miller, BW., Kwitkowski, VE., et al.[2022]

Citations

1.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/40736551/
Real-world efficacy and safety outcomes of acalabrutinib in ...NAOS, one of the largest real-world cohorts of acalabrutinib-treated CLL patients in Europe, showed effectiveness and safety consistent with ...
Real-World Effectiveness and Safety Outcomes of ...Acalabrutinib Induces Durable Remission in Patients With Treatment Naïve Chronic Lymphocytic Leukemia. ASH Clinical News, 2021. 2SPD-025 ...
How Effective Is CALQUENCE® (acalabrutinib)? | CLL92% (165 of 179) of people on CALQUENCE + immunotherapy* had no cancer growth or spread compared to 47% (84 of 177) of people on chemoimmunotherapy.†. 80% Down ...
Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic ...At a median follow-up of 14.3 months, the overall response rate was 95%, including 85% with a partial response and 10% with a partial response ...
Meta-analysis of the efficacy and adverse effects ...Literature to date has shown acalabrutinib has a high overall response rate (ORR), including in CLL patients with high-risk disease. The ORR for ...
NCT04008706 | Acalabrutinib Safety Study in Untreated ...To evaluate the safety and tolerability of acalabrutinib monotherapy in participants with treatment-naïve or relapsed/refractory chronic lymphocytic leukemia.
Safety Profile of Acalabrutinib Superior to ...The cardiovascular safety profile of acalabrutinib is superior to that of chemoimmunotherapy in treating patients with chronic lymphocytic leukemia (CLL).
8.calquence.comcalquence.com/
Treatment for CLL/SLL and R/R MCL | CALQUENCE ...Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). It is not known if CALQUENCE is safe and effective in children. Please see full ...
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