Acalabrutinib + Obinutuzumab + Chlorambucil for Chronic Lymphocytic Leukemia

(ElevateTN Trial)

Recruiting at 277 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Acerta Pharma BV

Must not be taking: Corticosteroids, Anticoagulants, PPIs, CYP3A inhibitors

Disqualifiers: Prior CLL treatment, CNS lymphoma, Cardiovascular disease, others

No Placebo Group All 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 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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 cycles

535 Participants Needed

Trial Summary

What is the purpose of this trial?

This Primary objective is evaluating the efficacy of obinutuzumab in combination with chlorambucil (Arm A) compared with acalabrutinib in combination with obinutuzumab (Arm B) for the treatment of previously untreated chronic lymphocytic leukemia (CLL). Secondary objectives: 1) To evaluate the efficacy of obinutuzumab in combination with chlorambucil (Arm A) versus acalabrutinib monotherapy (Arm C) based on IRC assessment of PFS per IWCLL 2008 criteria. 2)To compare obinutuzumab plus chlorambucil (Arm A) versus acalabrutinib plus obinutuzumab (Arm B) and obinutuzumab plus chlorambucil (Arm A) versus acalabrutinib monotherapy (Arm C) in terms of: IRC-assessed objective response rate (ORR); Tine to next treatment (TTNT); Overall Survival (OS)

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.

What data supports the effectiveness of the drug combination Acalabrutinib, Obinutuzumab, and Chlorambucil for treating chronic lymphocytic leukemia?

Research shows that Acalabrutinib, especially when combined with Obinutuzumab, is effective in treating chronic lymphocytic leukemia (CLL). It has been shown to significantly extend the time patients live without the disease getting worse compared to standard treatments like Chlorambucil with Obinutuzumab. Additionally, Acalabrutinib has a favorable safety profile, making it a promising option for patients with CLL. ^{1 2 3 4 5}

How is the drug combination of Acalabrutinib, Obinutuzumab, and Chlorambucil unique for treating chronic lymphocytic leukemia?

This drug combination is unique because Acalabrutinib is a highly selective Bruton tyrosine kinase inhibitor that, when combined with Obinutuzumab, shows improved safety and efficacy compared to other treatments. It offers a longer progression-free survival and a favorable safety profile, making it a promising option for patients with chronic lymphocytic leukemia. ^{1 2 3 5 6}

Research Team

AstraZeneca Clinical Study Information Center

Principal Investigator

1-877-240-9479 [e-mail]

Eligibility Criteria

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.

Exclusion Criteria

I am currently taking warfarin or a similar blood thinner.

Concurrent participation in another therapeutic clinical trial

I have been diagnosed with prolymphocytic leukemia or Richter's syndrome.

Timeline

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

Treatment Details

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.

Participant Groups

Group I: Arm C - Acalabrutinib Monotherapy Experimental Treatment 1 Intervention

Acalabrutinib (ACP-196) will be orally administered on Cycle 1 Day 1 until disease progression or unacceptable toxicity.

Group II: Arm B - Acalabrutinib in Combination with Obinutuzumab Experimental Treatment 2 Interventions

Obinutuzumab IV infusions will be administered over a total of 6 treatment cycles starting at Cycle 2 Day 1. Acalabrutinib (ACP-196) will be orally administered starting on Cycle 1 Day 1. Daily administration of Acalabrutinib (ACP-196) will continue until disease progression or unacceptable toxicity.

Group III: Arm A - Obinutuzumab in Combination with Chlorambucil Active Control 2 Interventions

Obinutuzumab IV infusions will be administered over a total of 6 treatment cycles starting at Cycle 1 Day 1. Chlorambucil will be orally administered on Days 1 and 15 of Cycles 1 through 6.

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

Approved in United States as Calquence for:

• Mantle cell lymphoma
• Chronic lymphocytic leukemia
• Small lymphocytic lymphoma

Approved in European Union as Calquence for:

• Chronic lymphocytic leukemia
• Small lymphocytic lymphoma
• Mantle cell lymphoma

Who Is Running the Clinical Trial?

Acerta Pharma BV

Lead Sponsor

Trials

46

Recruited

5,900+

Findings from Research

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

Acalabrutinib has been approved in the EU for treating both treatment-naïve and relapsed/refractory chronic lymphocytic leukemia (CLL), showing significant improvements in progression-free survival compared to standard therapies in two phase III trials involving adult patients.

The safety profile of acalabrutinib is generally acceptable, with common side effects including headache, diarrhea, and infections, and the overall benefit-risk ratio is considered positive for its use in CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EMA Review of Acalabrutinib for the Treatment of Adult Patients with Chronic Lymphocytic Leukemia. Delgado, J., Josephson, F., Camarero, J., 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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

In a multinational phase III study, obinutuzumab combined with chlorambucil significantly improved progression-free survival and event-free survival in adults with previously untreated chronic lymphocytic leukaemia (CLL) compared to chlorambucil alone and rituximab plus chlorambucil.

Obinutuzumab plus chlorambucil had a manageable safety profile, with neutropenia and infusion-related reactions being the most common serious side effects, primarily occurring during the first infusion and generally manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab: a review of its use in patients with chronic lymphocytic leukaemia. Hoy, SM.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Matching-adjusted indirect comparisons of safety and efficacy of acalabrutinib versus other targeted therapies in patients with treatment-naïve chronic lymphocytic leukemia. [2021]

2. England pubmed.ncbi.nlm.nih.gov

EMA Review of Acalabrutinib for the Treatment of Adult Patients with Chronic Lymphocytic Leukemia. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

U.S. Food and drug administration approval: obinutuzumab in combination with chlorambucil for the treatment of previously untreated chronic lymphocytic leukemia. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Quality-adjusted survival time without symptoms or toxicity of acalabrutinib with or without obinutuzumab in patients with treatment-naive chronic lymphocytic leukemia. [2023]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Obinutuzumab: a review of its use in patients with chronic lymphocytic leukaemia. [2018]