AU2 for Chronic Lymphocytic Leukemia

Recruiting at 2 trial locations

Overseen By Jennifer R Brown, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Jennifer R. Brown, MD, PhD

Must be taking: Anti-pneumocystis, Antiviral

Must not be taking: CYP3A4 inhibitors, Proton pump inhibitors

Disqualifiers: CNS involvement, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 1

Duration: 24 cycles (approximately 2 years)

29 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does mention that you cannot take certain medications like strong inhibitors or inducers of CYP3A4 and proton pump inhibitors. It's best to discuss your current medications with the study team to see if any adjustments are needed.

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

Research shows that Acalabrutinib, a drug that blocks a protein important for cancer cell growth, significantly extends the time patients with chronic lymphocytic leukemia live without their disease getting worse compared to standard treatments. It has been approved in the European Union for both newly diagnosed patients and those whose disease has returned or not responded to previous treatments. ^{1 2 3 4 5}

What is the purpose of this trial?

This study is testing the effectiveness of the study drug combination of acalabrutinib, umbralisib, and ublituximab in participants with Chronic Lymphocytic leukemia (CLL). The names of the study drugs involved in this study are/is: * Acalabrutinib (CALQUENCE®, ACP-196) * Umbralisib (TGR-1202) * Ublituximab (TG-1101)

Research Team

Jennifer R Brown, MD, PhD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults with Chronic Lymphocytic Leukemia (CLL) who either have relapsed after treatment or haven't been treated before. Participants should be in relatively good health, able to take oral medication, and willing to use effective contraception. Those with more than two prior cancer treatments, recent major surgery, certain blood disorders, active infections like Hepatitis B/C or HIV are excluded.

Inclusion Criteria

My disease has not been treated before.

My heart function is classified as class 2B or better.

I have CLL that has come back or didn't respond to treatment, and I've had 2 or fewer prior treatments.

Exclusion Criteria

Allergic reactions attributed to study drugs or compounds of similar chemical or biologic composition

I am not taking strong drugs that affect liver enzyme CYP3A4.

I do not have active Hepatitis B or C, cytomegalovirus, or HIV.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Acalabrutinib, Umbralisib, and Ublituximab for a maximum of 24 cycles

24 cycles (approximately 2 years)

Visits at cycle 1 day 1, 8, and 15, cycle 2-6 and cycle 8-25 day 1, and cycle 7 day 1, 2 and 8

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• Acalabrutinib
• Ublituximab
• Umbralisib

Trial Overview The study tests a combination of three drugs: Acalabrutinib (CALQUENCE®), Umbralisib (TGR-1202), and Ublituximab (TG-1101). It aims to determine their effectiveness in treating CLL when used together. The trial includes people who have had previous treatments as well as those who are untreated.

Participant Groups

Group I: Cohort 2-Treatment Naive Experimental Treatment 3 Interventions

Participants with previously untreated disease * Treatment with Acalabrutinib \& Umbralisib beginning C1D1, * Ublituximab beginning C7D1 * Assessment of treatment response * Treatment continues for a maximum of 24 cycles. Participants followed post treatment for a maximum of 5 years

Group II: Cohort 1-Relapsed Disease Experimental Treatment 3 Interventions

Participants with relapsed disease * Treatment with Acalabrutinib \& Umbralisib beginning C1D1, * Ublituximab beginning C7D1 * Assessment of treatment response * Treatment continues for a maximum of 24 cycles. Participants followed post treatment for a maximum of 5 years

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?

Jennifer R. Brown, MD, PhD

Lead Sponsor

Trials

3

Recruited

140+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

TG Therapeutics, Inc.

Industry Sponsor

Trials

41

Recruited

6,900+

Findings from Research

In a phase III study involving 310 patients with relapsed/refractory chronic lymphocytic leukemia (CLL), acalabrutinib monotherapy significantly improved progression-free survival (PFS) compared to investigator's choice treatments, with a median PFS not reached for acalabrutinib versus 16.5 months for the comparator group.

Acalabrutinib demonstrated a favorable safety profile, with serious adverse events occurring in 29% of patients, compared to 56% for idelalisib plus rituximab and 26% for bendamustine plus rituximab, indicating it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia. Ghia, P., Pluta, A., Wach, M., 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]

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]

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]

In a pivotal phase 3 study with 310 patients, acalabrutinib significantly improved progression-free survival (PFS) compared to standard treatments (Idelalisib plus rituximab or bendamustine plus rituximab), with a median PFS not reached for acalabrutinib versus 16.8 months for IdR/BR.

After approximately 4 years of follow-up, acalabrutinib demonstrated a favorable safety profile, with lower rates of treatment discontinuation due to adverse events compared to IdR/BR, while maintaining similar rates of serious infections and other significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib Versus Investigator's Choice in Relapsed/Refractory Chronic Lymphocytic Leukemia: Final ASCEND Trial Results. Ghia, P., Pluta, A., Wach, M., et al.[2022]

References

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

ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory 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. 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]

4. 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]

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

Acalabrutinib Versus Investigator's Choice in Relapsed/Refractory Chronic Lymphocytic Leukemia: Final ASCEND Trial Results. [2022]