60 Participants Needed

Acalabrutinib + Obinutuzumab for Chronic Lymphocytic Leukemia

JA
Overseen ByJan A Burger, MD
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: M.D. Anderson Cancer Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
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

Trial Summary

What is the purpose of this trial?

This phase II trial investigates the how well acalabrutinib and obinutuzumab work in treating patients with chronic lymphocytic leukemia (CLL). Acalabrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with obinutuzumab may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving acalabrutinib and obinutuzumab may help to control disease progression in CLL patients who have not received treatment for CLL.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take warfarin (a blood thinner) and must switch to a different type of blood thinner if needed. Also, you cannot use strong CYP3A4 inhibitors/inducers (types of drugs that affect how your body processes medications).

What data supports the effectiveness of the drug Acalabrutinib plus Obinutuzumab for Chronic Lymphocytic Leukemia?

Research shows that Acalabrutinib, when used with Obinutuzumab, is effective in treating chronic lymphocytic leukemia, with high response rates and a significant number of patients remaining free from disease progression after 36 months. This combination has been shown to be well-tolerated and provides durable responses in both newly diagnosed and previously treated patients.12345

Is the combination of Acalabrutinib and Obinutuzumab safe for treating chronic lymphocytic leukemia?

The combination of Acalabrutinib and Obinutuzumab has been shown to be generally safe for treating chronic lymphocytic leukemia, with common side effects including headache, diarrhea, neutropenia (low white blood cell count), nausea, and infections. Infusion-related reactions are more common with Obinutuzumab, but these are usually mild to moderate and manageable. Overall, the safety profile is considered acceptable.12567

What makes the drug combination of Acalabrutinib and Obinutuzumab unique for treating chronic lymphocytic leukemia?

The combination of Acalabrutinib and Obinutuzumab is unique because Acalabrutinib is a highly selective Bruton tyrosine kinase inhibitor, which means it specifically targets a protein important for cancer cell survival, while Obinutuzumab is an antibody that enhances the immune system's ability to attack cancer cells. This combination has shown to be well-tolerated and effective, providing durable responses in patients with chronic lymphocytic leukemia, both in those who are newly diagnosed and those whose disease has returned.12458

Research Team

JA

Jan A. Burger

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for patients with chronic lymphocytic leukemia (CLL) who haven't been treated before. They should have a creatinine clearance over 30 mL/min, normal liver function tests, and no prior malignancies within the last 2 years except certain skin cancers or 'in situ' carcinomas. Participants must be willing to use effective birth control and not be pregnant or breastfeeding. People with previous CLL treatments, significant infections, uncontrolled heart conditions, recent strokes or surgeries are excluded.

Inclusion Criteria

Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) except for patients with bilirubin elevation due to Gilbert's disease who will be allowed to participate
I have been diagnosed with CLL/SLL and have not received any treatment.
I am able to care for myself and perform daily activities.
See 6 more

Exclusion Criteria

I have not had major surgery or a serious injury in the last 28 days.
I need treatment with a strong medication that affects liver enzymes.
I can't swallow pills or have a stomach condition affecting medication absorption.
See 17 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive acalabrutinib orally twice a day and obinutuzumab intravenously, with treatment repeating every 28 days for up to 24 cycles

24 months
Monthly visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

4 years
1 visit at 30 days post-treatment, then every 3 months

Optional Extension

Participants who do not achieve a complete response may receive additional cycles of acalabrutinib and obinutuzumab

6 months

Treatment Details

Interventions

  • Acalabrutinib
  • Obinutuzumab
Trial OverviewThe trial is testing how well acalabrutinib combined with obinutuzumab works in treating CLL. Acalabrutinib blocks enzymes needed for tumor growth while obinutuzumab may help the immune system interfere with tumor cell growth and spread. The goal is to see if this combination can better manage disease progression in untreated CLL patients.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment (acalabrutinib, obinutuzumab)Experimental Treatment2 Interventions
Patients receive acalabrutinib PO BID every 12 hours starting on day 1 of cycle 1, and obinutuzumab IV over 4-6 hours on days 1 and 2 of cycle 3, and day 1 of cycles 4-8. Patients who do not achieve a complete response or remission after cycle 8 may receive single-agent acalabrutinib therapy PO BID for an additional 6 cycles at the discretion of their treating physician. Patients who are in partial response or who have stable disease receive an additional 6 cycles of acalabrutinib PO BID and obinutuzumab IV. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

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

Find a Clinic Near You

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials
3,107
Recruited
1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

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

References

Matching-adjusted indirect comparisons of safety and efficacy of acalabrutinib versus other targeted therapies in patients with treatment-naïve chronic lymphocytic leukemia. [2021]
EMA Review of Acalabrutinib for the Treatment of Adult Patients with Chronic Lymphocytic Leukemia. [2021]
U.S. Food and drug administration approval: obinutuzumab in combination with chlorambucil for the treatment of previously untreated chronic lymphocytic leukemia. [2022]
Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. [2021]
Acalabrutinib plus Obinutuzumab in Treatment-Naïve and Relapsed/Refractory Chronic Lymphocytic Leukemia. [2022]
Obinutuzumab: a review of its use in patients with chronic lymphocytic leukaemia. [2018]
Managing Infusion-Related Reactions for Patients With Chronic Lymphocytic Leukemia Receiving Obinutuzumab. [2017]
ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia. [2021]