Chronic lymphocytic leukemia/small lymphocytic lymphoma

Summary

Chronic lymphocytic leukemia/small lymphocytic lymphoma (MONDO:0003864) is a cancer with 2 cohort genes (2 CIViC-evidence somatic drivers) and 56 clinical trials. Molecularly, BCL2 A113G is associated with resistance to Venetoclax in Chronic Lymphocytic Leukemia/small Lymphocytic Lymphoma (CIViC Level B); 7 further subtype–drug associations are mapped below. Top therapeutic interventions include fludarabine phosphate, acalabrutinib, and epcoritamab.

At a glance

• Classification: Cancer
• Cohort genes: 2
• Clinical trials: 56
• Precision-medicine evidence (CIViC): 8 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	chronic lymphocytic leukemia/small lymphocytic lymphoma
Mondo ID	MONDO:0003864
DOID	DOID:6354
NCIT	C27911
UMLS	C1302547
MedGen	224906
GARD	0023704
Is cancer (heuristic)	yes

Also known as: chronic lymphocytic leukemia/small lymphocytic lymphoma · chronic lymphocytic leukemia/small lymphocytic lymphoma (morphologic abnormality) · CLL/SLL

Data availability: 52 intOGen driver records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › hematopoietic and lymphoid system neoplasm › hematopoietic and lymphoid cell neoplasm › leukemia › chronic leukemia › B-cell chronic lymphocytic leukemia › chronic lymphocytic leukemia/small lymphocytic lymphoma

Related subtypes (1): hairy cell leukemia

Subtypes (2): chronic lymphocytic leukemia/small lymphocytic lymphoma with immunoglobulin heavy chain variable-region gene somatic hypermutation, pregerminal center chronic lymphocytic leukemia/small lymphocytic lymphoma

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 23 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
TP53	LoF	ACC,ALL,AML,ANGS,ANSC,BCC,BL,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,EGC,ES,ESCA,ESCC,GB,GBC,GBM,GIST,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LNM,LUAD,LUSC,MBL,MEL,MLYM,MT,NBL,NETNOS,NHL,NPC,NSCLC,OS,OVT,PAAD,PANCREAS,PAST,PCM,PLMESO,PRAD,PRCC,PROSTATE,RCC,READ,SACA,SARCNOS,SCLC,SIC,SKCM,SKIN,SOFT_TISSUE,STAD,STOMACH,THYM,UCEC,UCS,UTUC,VULVA,WDTC,WT	CIViC #45
BCL2	Act	DLBCLNOS,MLYM,NHL	CIViC #59

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TP53	Orphanet:1333	Familial pancreatic carcinoma
TP53	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
TP53	Orphanet:1501	Adrenocortical carcinoma
TP53	Orphanet:210159	Adult hepatocellular carcinoma
TP53	Orphanet:251576	Gliosarcoma
TP53	Orphanet:251579	Giant cell glioblastoma
TP53	Orphanet:251899	Choroid plexus carcinoma
TP53	Orphanet:2807	Papilloma of choroid plexus
TP53	Orphanet:293199	Pleomorphic rhabdomyosarcoma
TP53	Orphanet:3318	Essential thrombocythemia
TP53	Orphanet:524	Li-Fraumeni syndrome
TP53	Orphanet:52688	Myelodysplastic syndrome
TP53	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
TP53	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
TP53	Orphanet:668	Osteosarcoma
TP53	Orphanet:67038	B-cell chronic lymphocytic leukemia
TP53	Orphanet:70573	Small cell lung cancer
TP53	Orphanet:96253	Cushing disease
TP53	Orphanet:99756	Alveolar rhabdomyosarcoma
TP53	Orphanet:99757	Embryonal rhabdomyosarcoma
BCL2	Orphanet:480541	High grade B-cell lymphoma with MYC and/ or BCL2 and/or BCL6 rearrangement
BCL2	Orphanet:545	Follicular lymphoma
BCL2	Orphanet:98839	Intravascular large B-cell lymphoma

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	civic_evidence
BCL2	HGNC:990	ENSG00000171791	P10415	Apoptosis regulator Bcl-2	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
BCL2	Apoptosis regulator Bcl-2	Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	1	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
BCL2	Other/Unknown	no		Bcl2-like, Bcl2_BH4, Bcl2/BclX

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ganglionic eminence	1
tendon of biceps brachii	1
ventricular zone	1
calcaneal tendon	1
dorsal motor nucleus of vagus nerve	1
superficial temporal artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
BCL2	275	ubiquitous	marker	dorsal motor nucleus of vagus nerve, superficial temporal artery, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
BCL2	8,343

Intra-cohort edges

A	B	Sources
BCL2	TP53	intact, string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TP53	P04637	313
BCL2	P10415	55

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 75. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Loss of function of TP53 in cancer due to loss of tetramerization ability	1	5710.0×	0.007	TP53
Interleukin-4 and Interleukin-13 signaling	2	102.9×	0.007	TP53, BCL2
Regulation of TP53 Expression	1	2855.0×	0.009	TP53
The NLRP1 inflammasome	1	1903.3×	0.010	BCL2
Transcriptional activation of cell cycle inhibitor p21	1	1427.5×	0.010	TP53
Activation of NOXA and translocation to mitochondria	1	951.7×	0.010	TP53
RUNX3 regulates CDKN1A transcription	1	815.7×	0.010	TP53
BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members	1	634.4×	0.010	BCL2
PI5P Regulates TP53 Acetylation	1	634.4×	0.010	TP53
Activation of PUMA and translocation to mitochondria	1	571.0×	0.010	TP53
Inflammasomes	1	571.0×	0.010	BCL2
TP53 Regulates Transcription of Caspase Activators and Caspases	1	475.8×	0.010	TP53
TP53 Regulates Transcription of Death Receptors and Ligands	1	475.8×	0.010	TP53
NFE2L2 regulating tumorigenic genes	1	475.8×	0.010	BCL2
Urea cycle	1	439.2×	0.010	TP53
Regulation of TP53 Activity through Association with Co-factors	1	407.9×	0.010	TP53
Activation of BAD and translocation to mitochondria	1	380.7×	0.010	BCL2
TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain	1	380.7×	0.010	TP53
Stabilization of p53	1	380.7×	0.010	TP53
TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest	1	356.9×	0.010	TP53
Formation of Senescence-Associated Heterochromatin Foci (SAHF)	1	335.9×	0.010	TP53
Zygotic genome activation (ZGA)	1	335.9×	0.010	TP53
Regulation of NF-kappa B signaling	1	317.2×	0.010	TP53
Regulation of MITF-M-dependent genes involved in apoptosis	1	317.2×	0.010	BCL2
TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest	1	300.5×	0.010	TP53
SUMOylation of transcription factors	1	285.5×	0.010	TP53
TP53 Regulates Transcription of Genes Involved in Cytochrome C Release	1	271.9×	0.010	TP53
Regulation of TP53 Activity through Methylation	1	271.9×	0.010	TP53
TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain	1	259.6×	0.010	TP53
Activation of BH3-only proteins	1	248.3×	0.010	BCL2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
B cell lineage commitment	2	3370.4×	2e-05	TP53, BCL2
hematopoietic stem cell differentiation	2	766.0×	1e-04	TP53, BCL2
release of cytochrome c from mitochondria	2	702.2×	1e-04	TP53, BCL2
response to gamma radiation	2	581.1×	2e-04	TP53, BCL2
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	2	481.5×	2e-04	TP53, BCL2
reactive oxygen species metabolic process	2	468.1×	2e-04	TP53, BCL2
T cell differentiation in thymus	2	411.0×	2e-04	TP53, BCL2
cellular response to glucose starvation	2	337.0×	2e-04	TP53, BCL2
response to ischemia	2	251.5×	4e-04	TP53, BCL2
neuron apoptotic process	2	185.2×	7e-04	TP53, BCL2
negative regulation of cell growth	2	144.0×	1e-03	TP53, BCL2
cellular response to hypoxia	2	121.2×	0.001	TP53, BCL2
melanin metabolic process	1	8426.0×	0.001	BCL2
obsolete negative regulation of cellular pH reduction	1	8426.0×	0.001	BCL2
pigment granule organization	1	8426.0×	0.001	BCL2
negative regulation of helicase activity	1	8426.0×	0.001	TP53
cellular response to actinomycin D	1	8426.0×	0.001	TP53
regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1	8426.0×	0.001	TP53
negative regulation of G1 to G0 transition	1	8426.0×	0.001	TP53
autophagy	2	110.1×	0.001	TP53, BCL2
regulation of nitrogen utilization	1	4213.0×	0.002	BCL2
positive regulation of mitochondrial membrane permeability	1	4213.0×	0.002	TP53
CD8-positive, alpha-beta T cell lineage commitment	1	4213.0×	0.002	BCL2
negative regulation of retinal cell programmed cell death	1	4213.0×	0.002	BCL2
oligodendrocyte apoptotic process	1	4213.0×	0.002	TP53
negative regulation of glucose catabolic process to lactate via pyruvate	1	4213.0×	0.002	TP53
negative regulation of pentose-phosphate shunt	1	4213.0×	0.002	TP53
positive regulation of neuron maturation	1	2808.7×	0.002	BCL2
obsolete homolactic fermentation	1	2808.7×	0.002	TP53
cochlear nucleus development	1	2808.7×	0.002	BCL2

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 0

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
TP53	NITROFURANTOIN
BCL2	IXABEPILONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
BCL2	14	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53
AMITRIPTYLINE HYDROCHLORIDE	4	TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	TP53
PROCHLORPERAZINE EDISYLATE	4	TP53
DEQUALINIUM CHLORIDE	4	TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
BCL2	446	Binding:418, Functional:23, Toxicity:3, ADMET:2

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
TP53	869
BCL2	446

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Drug repurposing candidates

30 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Compound	Max phase	Cohort target (bioactivity)
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53
AMITRIPTYLINE HYDROCHLORIDE	4	TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	TP53
PROCHLORPERAZINE EDISYLATE	4	TP53
DEQUALINIUM CHLORIDE	4	TP53

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	TP53, BCL2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 56.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	23
Not specified	12
PHASE1	10
PHASE1/PHASE2	8
PHASE3	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06104566	PHASE3	RECRUITING	Global Trial in APG2575 for Patients With CLL/SLL
NCT06319456	PHASE3	RECRUITING	A Global Study of Lisaftoclax (APG-2575) Combined With Acalabrutinib Versus Immunochemotherapy for Newly Diagnosed CLL/SLL.
NCT07139873	PHASE3	RECRUITING	A Study of DZD8586 Versus Investigator’s Choice in r/r CLL/SLL (TAI-SHAN6)
NCT04458610	PHASE2	ACTIVE_NOT_RECRUITING	Zanubrutinib and Rituximab for the Treatment of Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
NCT04523428	PHASE2	RECRUITING	REtreatment With VEnetoclax and Acalabrutinib After Venetoclax Limited Duration (REVEAL)
NCT04657094	PHASE2	ACTIVE_NOT_RECRUITING	Acalabrutinib for the Treatment of Relapsed or Refractory Autoimmune Hemolytic Anemia in Patients With Chronic Lymphocytic Leukemia
NCT05294731	PHASE1/PHASE2	RECRUITING	Treatment of Chinese Participants With B-Cell Malignancies With BGB-16673, a Bruton Tyrosine Kinase-Targeted Protein-Degrader
NCT05479994	PHASE2	ACTIVE_NOT_RECRUITING	Study of BGB-11417 in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
NCT05643742	PHASE1/PHASE2	RECRUITING	A Safety and Efficacy Study Evaluating CTX112 in Subjects With Relapsed or Refractory B-Cell Malignancies
NCT05791409	PHASE1/PHASE2	RECRUITING	Venetoclax Treatment (26 Cycles) With 6 Cycles or 12 Cycles of Epcoritamab in Patients With Relapsed or Refractory CLL or SLL
NCT05918276	PHASE2	NOT_YET_RECRUITING	Clinical Study of Orelabrutinib Combined With BG Regimen First-line Treatment of CLL/SLL
NCT06476899	PHASE2	NOT_YET_RECRUITING	A Practical Clinical Study Comparing the Fixed-cycle Regimen Containing Orelabrutinib With BTKi Monotherapy
NCT06539182	PHASE2	RECRUITING	DZD8586 in Patients With Relapsed or Refractory CLL/SLL (TAI-SHAN8)
NCT06757647	PHASE2	RECRUITING	Acalabrutinib for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
NCT06978088	PHASE2	RECRUITING	LP-168 and Obinutuzumab for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) and Variants of This
NCT07108998	PHASE2	RECRUITING	Study of Epcoritamab as a Consolidation Therapy in CLL/SLL
NCT07154264	PHASE2	RECRUITING	A Study of DZD8586 Combination in CLL/SLL (TAI-SHAN10)
NCT07194980	PHASE2	RECRUITING	Nemtabrutinib and Lisocabtagene Maraleucel for the Treatment of Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
NCT07523555	PHASE1/PHASE2	RECRUITING	Adaptive Dual-Target CAR-T Cells for Relapsed or Refractory Hematologic Malignancies
NCT07582159	PHASE2	NOT_YET_RECRUITING	Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
NCT07609862	PHASE1/PHASE2	NOT_YET_RECRUITING	A Phase Ib/II Study of Rocbrutinib in Combination With Lacutoclax in Patients With B-Cell Malignancies
NCT00090090	PHASE2	COMPLETED	Elsamitrucin (SPI 28090) for Relapsed or Refractory Non-Hodgkin’s Lymphoma
NCT03041636	PHASE2	COMPLETED	Ruxolitinib Phosphate in Treating Patients With Previously Untreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
NCT03128359	PHASE2	COMPLETED	High Dose Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil in Preventing Graft Versus Host Disease in Patients With Hematological Malignancies Undergoing Myeloablative or Reduced Intensity Donor Stem Cell Transplant
NCT03493217	PHASE1/PHASE2	UNKNOWN	A Study to Evaluate ICP-022 in Patients With CLL/ SLL
NCT04116437	PHASE2	COMPLETED	Zanubrutinib (BGB-3111) in Participants With Previously Treated B-Cell Lymphoma Intolerant of Prior Bruton Tyrosine Kinase Inhibitor (BTKi) Treatment
NCT04149821	PHASE2	TERMINATED	Umbralisib Plus Ublituximab (U2) in Progressive CLL After Novel Therapy
NCT04230304	PHASE2	TERMINATED	Daratumumab and Ibrutinib for the Treatment of Relapsed or Refractory Chronic Lymphocytic Leukemia, DIRECT Study
NCT04660045	PHASE2	WITHDRAWN	Early Intervention With Acalabrutinib in Patients With High Risk CLL
NCT04665115	PHASE2	WITHDRAWN	Ibrutinib for the Treatment of Patients With B-Cell Malignancies Who Are Infected With Coronavirus Disease 2019 (COVID-19)
NCT05269940	PHASE1/PHASE2	COMPLETED	A Study to Evaluate Activity, Safety and Tolerability of ZX-101A in Relapsed/Refractory Hematological Malignancies
NCT05322733	PHASE2	UNKNOWN	Orelabrutinib and Obinutuzumab Plus FC Regimen in Treating Newly Diagnosed CLL/SLL
NCT05365100	PHASE1/PHASE2	WITHDRAWN	A Study of BN102 in Patients With Previously Treated CLL/SLL and B-cell NHL
NCT05491044	PHASE2	UNKNOWN	A Study of Orelabrutinib in CLL/SLL Patients Who Are Slowly Responding to Ibrutinib
NCT04215809	PHASE1	RECRUITING	Study of APG-2575 as a Single Agent or in Combination With Other Therapeutic Agents for CLL/SLL
NCT04775745	PHASE1	RECRUITING	Study of Oral Administration of LP-168 in Patients With Relapsed or Refractory B-cell Malignancies.
NCT05665062	PHASE1	ACTIVE_NOT_RECRUITING	Autologous CD19 CAR-T Cell Therapy (SYNCAR-001) + Orthogonal IL-2 (STK-009) in Subjects With CD19+ Hematologic Malignancies
NCT06859008	PHASE1	RECRUITING	Zanubrutinib in Combination With Sonrotoclax for the Treatment of Underrepresented Ethnic and Racial Minorities With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma
NCT02268851	PHASE1	COMPLETED	A Phase I/Ib Safety and Efficacy Study of the PI3K-delta Inhibitor TGR-1202 and Ibrutinib in Patients With CLL or MCL
NCT02960646	PHASE1	COMPLETED	Engineered Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
FLUDARABINE PHOSPHATE	4	5
ACALABRUTINIB	4	4
EPCORITAMAB	4	2
UMBRALISIB	4	2
ZANUBRUTINIB	4	2
BENDAMUSTINE	4	1
CHLORAMBUCIL	4	1
DUVELISIB	4	1
IDELALISIB	4	1
MELPHALAN	4	1
RUXOLITINIB	4	1
TAFASITAMAB	4	1
UBLITUXIMAB	4	1
ORELABRUTINIB	3	5
SONROTOCLAX	3	2
FLUDARABINE	3	1
LISOCABTAGENE MARALEUCEL	3	1
NEMTABRUTINIB	3	1
APG-2575	2	3
ELSAMITRUCIN	2	1
LACUTOCLAX	2	1
ROCBRUTINIB	2	1
CHEMBL4747506	0	4
CHEMBL5187554	0	4
CHEMBL5276925	0	4
CHEMBL5567397	0	3
CHEMBL5193128	0	2
CHEMBL290077	0	1
CHEMBL4095008	0	1
CHEMBL5170320	0	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 8 predictive associations from 8 curated evidence items.

Molecular subtype	Therapy	Effect	Level	CIViC
BCL2 A113G	Venetoclax	Resistance	CIViC B	EID8189
BCL2 F104L	Venetoclax	Resistance	CIViC B	EID8187
BCL2 F104S	Venetoclax	Resistance	CIViC B	EID8186
BCL2 G101A	Venetoclax	Resistance	CIViC B	EID8184
BCL2 L119V	Venetoclax	Resistance	CIViC B	EID8190
BCL2 R107_R110dup	Venetoclax	Resistance	CIViC B	EID8188
TP53 Mutation	Venetoclax	Resistance	CIViC B	EID6074
BCL2 G101V	Venetoclax	Resistance	CIViC C	EID8185