Chlorambucil
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | DRUG-CHLORAMBUCIL |
|---|---|
| Type | Drug |
| Aliases | CB-1348LeukeranХлорамбуцил |
| Status | reviewed 2026-04-27 | pending_clinical_signoff |
| Diseases | DIS-CLL |
| Sources | SRC-ESMO-CLL-2024 SRC-NCCN-BCELL-2025 |
Drug Facts
| Class | Alkylating agent — nitrogen mustard |
|---|---|
| Mechanism | Bifunctional alkylating agent of the nitrogen-mustard class. Aromatic nitrogen mustard with a phenylbutyric-acid carrier; less reactive (and therefore better orally bioavailable + less acutely toxic) than classical nitrogen mustards. Forms aziridinium intermediates that alkylate the N7 position of guanine, generating intra- and interstrand DNA cross-links → blocked replication, transcription, and apoptosis (preferentially in slowly-dividing lymphoid cells). Cell-cycle non-specific. Used for decades in CLL (now largely supplanted by BTK and BCL2 inhibitors), Waldenström, and as the partner of obinutuzumab in elderly comorbid CLL (CLL11 trial). |
| Typical dosing | CLL11 (obinutuzumab + chlorambucil, elderly comorbid CLL 1L): 0.5 mg/kg PO on days 1 and 15 of each 28-day cycle × 6 cycles. Monotherapy CLL (historical): 0.1-0.2 mg/kg PO daily continuous OR 0.4 mg/kg PO every 2 weeks (escalate by 0.1 mg/kg until response or myelosuppression). Waldenström: 0.1 mg/kg PO daily until best response. Take on empty stomach (food reduces bioavailability ~10-20%). |
| Ukraine registered | True |
| NSZU reimbursed | True |
| Ukraine last verified | 2026-04-27 |
Warnings
- Secondary malignancies — therapy-related AML / MDS (cumulative dose >0.4 g/m² substantially increases risk; latency 4-7 years)
- Severe + prolonged myelosuppression (especially cumulative; recovery may take weeks-months)
- Infertility (azoospermia, ovarian failure — often permanent; counsel on fertility preservation before therapy)
- Mutagenicity / carcinogenicity (genotoxic; long-term cancer risk)
Notes
CLL11 (Goede 2014, NEJM): obinutuzumab + chlorambucil vs rituximab + chlorambucil vs chlorambucil alone in previously-untreated CLL with comorbidities (CIRS >6 OR CrCl 30-69) — mPFS 26.7 vs 15.2 vs 11.1 mo. Established G-Clb as a fitness-tailored 1L for elderly comorbid CLL. Now positioned behind venetoclax-obinutuzumab and BTK-inhibitor monotherapy in most NCCN/ESMO algorithms, but remains relevant for patients without access to those agents OR with contraindications to them. Long history (since 1957) — most familiar oral chemotherapy in community haematology. Counsel on infertility and secondary-malignancy risk before initiating; consider sperm banking / oocyte cryopreservation for younger patients (uncommonly used in this age group). TLS prophylaxis (allopurinol + hydration) for high-burden disease at cycle 1.
Used By
Indications
IND-CLL-ELDERLY-O-CHL- IND-CLL-ELDERLY-O-CHL
Regimens
REG-O-CHL- Obinutuzumab + Chlorambucil (G-Clb, CLL11 — elderly comorbid CLL 1L)