Calquence (acalabrutinib)

P2, N=63, Active, not recruiting, Sunnybrook Health Sciences Centre | Trial primary completion date: Dec 2024 --> Dec 2025

Successful fixed-duration regimens in CLL should achieve deep remission (i.e., undetectable minimal residual disease), sustain long-term progression-free survival, decrease the burden of treatment-related adverse events, and allow for re-treatment with minimal risk of drug resistance. Although fixed-duration treatment represents a positive step forward for most patients with CLL/SLL, the currently approved regimens often fall short in patients at high risk of progression. Continued research and development of next-generation drugs is essential to enhance efficacy and safety, ultimately improving outcomes in all patients with CLL/SLL.

P3, N=394, Recruiting, Guangzhou Lupeng Pharmaceutical Company LTD.

P2, N=28, Active, not recruiting, Patrick C. Johnson, MD | Recruiting --> Active, not recruiting

P2, N=96, Completed, BeiGene | Active, not recruiting --> Completed

Covalent BTK inhibitors (ibrutinib, acalabrutinib, and zanubrutinib) irreversibly bind the C481 residue and have produced high response rates and durable disease control, often replacing chemoimmunotherapy in the relapsed setting and, for some entities, even in the first line. Non-covalent BTK inhibitors (e.g., pirtobrutinib) bind BTK independently of C481, can overcome classic C481-mediated resistance, and extend BTK pathway targeting into later lines of therapy. Overall, BTK inhibition has evolved into a versatile platform enabling long-term, often chemo-free management strategies.

In the phase 3 randomized SEQUOIA study (NCT03336333), zanubrutinib (arm A) demonstrated superior progression-free survival (PFS) compared with bendamustine-rituximab (BR; arm B) in patients with treatment-naive chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) without del(17p). In the phase 3 AMPLIFY study (NCT03836261), acalabrutinib-venetoclax with or without obinutuzumab demonstrated prolonged PFS vs chemoimmunotherapy (investigator's choice of fludarabine, cyclophosphamide, and rituximab [FCR] or BR) in patients with treatment-naive CLL without del(17p) or TP53 mutations...Zanubrutinib also demonstrated longer PFS whether adjusted for age (PFS-INV hazard ratio &lsqb;HR], 0.26; 95% CI, 0.13-0.54; P<.0003) or unadjusted (PFS-INV HR, 0.45; 95% CI, 0.23-0.88; P=.0197). These results highlight zanubrutinib monotherapy as an effective treatment option for all patients with treatment-naive CLL/SLL, including patients who might otherwise be considered for more intensive fixed-duration combination regimens.

 This survey reveals evidence-based treatment selection and appropriate risk stratification in Indian hematology practice. The predominance of generic acalabrutinib reflects superior safety compared to ibrutinib and cost considerations. Financial constraints driving treatment discontinuation underscore an urgent need for healthcare policy interventions to improve drug accessibility and affordability, ensuring equitable access and optimal outcomes.

P=N/A, N=151, Active, not recruiting, AstraZeneca | Completed --> Active, not recruiting | Trial completion date: Jan 2025 --> Apr 2027 | Trial primary completion date: Jan 2025 --> Apr 2027

P2, N=80, Not yet recruiting, AstraZeneca | Trial completion date: Nov 2032 --> May 2029 | Initiation date: Sep 2025 --> Jan 2026 | Trial primary completion date: Nov 2032 --> May 2029

P1/2, N=72, Recruiting, Austin I Kim | N=53 --> 72 | Trial completion date: Jun 2026 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Jun 2027

P2, N=48, Completed, Acerta Pharma BV | Active, not recruiting --> Completed | Trial completion date: Apr 2026 --> Oct 2025