A Phase 2 interventional study of Lisaftoclax (APG-2575) and Rituximab in Richter Syndrome, sponsored by Institute of Hematology & Blood Diseases Hospital, China. Not yet recruiting at 6 sites in China. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-21.
Sponsored by Institute of Hematology & Blood Diseases Hospital, China · Phase 2, Interventional, and Treatment
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This single-arm, multicenter, open-label phase II trial evaluates the efficacy and safety of rituximab + pirtobrutinib + lisaftoclax + liposomal mitoxantrone in adults with CLL-transformed Richter syndrome (CLL-RS). All eligible patients receive 4 cycles (21 days each) of the quadruple regimen: rituximab 375 mg/m² IV on Day 0, pirtobrutinib 200 mg PO daily (D1-21), lisaftoclax ramp-up to 600 mg QD (D1-21), and liposomal mitoxantrone 18 mg/m² IV on D1, with TLS prophylaxis/monitoring. Primary endpoint: CR rate after 4 cycles. Secondary endpoints: ORR, DOR, PFS, OS, MRD negativity, and safety. Post-induction: CR/PR patients proceed to allo-HSCT, CAR-T, or maintenance; SD/PD receive alternative/palliative care. Long-term follow-up starts after discontinuation.
This single-arm, multicenter, open-label phase II trial evaluates the efficacy and safety of rituximab + pirtobrutinib + lisaftoclax + liposomal mitoxantrone in adults with CLL-transformed Richter syndrome (CLL-RS)。It is a innovative four-drug regimen combining rituximab, pirtobrutinib, lisaftoclax and liposomal mitoxantrone was designed, exerting synergistic anti-tumor effects through four distinct mechanisms: pirtobrutinib, a reversible non-covalent BTK inhibitor, overcomes BTK C481S-mediated drug resistance; lisaftoclax, a novel domestically developed BCL2 inhibitor, induces robust apoptosis independent of TP53 mutation status while carrying a lower risk of tumor lysis syndrome (TLS); liposomal mitoxantrone with low cardiac toxicity compensates for the insufficient cytotoxicity of targeted agents against highly proliferative tumor cells; and rituximab, an anti-CD20 monoclonal antibody, mediates dual immunological tumor killing. The entire study is divided into three phases: screening, treatment and follow-up. During the screening phase, a full set of baseline assessments must be completed within 30 days prior to enrollment, including pathological reconfirmation, IgHV clonal homology analysis, PET/CT scanning, bone marrow biopsy, organ function testing and TLS risk stratification. The treatment phase consists of four 21-day induction cycles with the following administration schedule: rituximab 375 mg/m² is intravenously infused on Day 0 of each cycle; pirtobrutinib 200 mg is orally administered once daily from Day 1 to Day 21; lisaftoclax is given via a stepwise dose ramp-up from 20 mg to 600 mg, followed by a daily maintenance dose of 600 mg; liposomal mitoxantrone 18 mg/m² is intravenously infused on Day 1 of each cycle. After completion of four induction cycles, subsequent therapeutic strategies are stratified by treatment response. Patients achieving complete response (CR) or partial response (PR) are prioritized for allogeneic hematopoietic stem cell transplantation (allo-HSCT); those ineligible for transplantation may receive sequential CAR-T cell therapy targeting CD19/BAFF-R. Patients unable to receive the above consolidation therapies will undergo two additional cycles of the four-drug regimen for consolidation, followed by one year of maintenance therapy with pirtobrutinib plus lisaftoclax. Patients with stable disease (SD) or progressive disease (PD) will switch to alternative anti-tumor regimens or receive palliative symptomatic treatment. Long-term follow-up is initiated upon treatment discontinuation until the end of the study period. Clear enrollment, exclusion, withdrawal and elimination criteria are predefined for this trial. Eligible patients must be aged ≥18 years, have an ECOG performance status score of 0-2, an estimated survival of more than 3 months, adequate function of all major organs, the ability to take oral medications, and full compliance with scheduled follow-up visits. Excluded subjects include those with transformation to non-DLBCL subtypes, non-CLL clonally unrelated lesions, central nervous system lymphoma involvement, prior exposure to pirtobrutinib/lisaftoclax, previous CAR-T therapy or allo-HSCT, uncontrolled severe active infection, severe cardiovascular and cerebrovascular diseases or bleeding history, concurrent requirement for strong CYP3A4/5 inhibitors or warfarin, pregnancy or lactation, hypersensitivity to any study drug, and cognitive or psychiatric disorders precluding study compliance. Subjects will be withdrawn from the trial if they experience disease progression after receiving at least two cycles of treatment, develop intolerable toxicities, voluntarily discontinue participation, or have an unplanned pregnancy. Subjects will be eliminated from analysis if they violate enrollment criteria, receive no study drug administration, lack valid evaluable laboratory data, or concurrently receive other anti-tumor agents. The primary efficacy endpoint of this study is the complete remission rate following four cycles of induction therapy, while secondary efficacy endpoints include best overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and bone marrow minimal residual disease (MRD) negative rate upon completion of four treatment cycles.
Institute of Hematology & Blood Diseases Hospital, China is the lead sponsor of 413 studies on the registry; 292 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria:
Inclusion Criteria
Adequate organ function as defined below:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorized to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorized to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Allogeneic and autologous transplant
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
This regimen adopts a 21-day treatment cycle, for a total of 4 cycles. Upon completion of the 4-cycle treatment, patients who achieve remission based on efficacy assessment results may receive sequential CAR-T therapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Drug: Lisaftoclax (APG-2575) · Drug: Rituximab · Drug: Pirtobrutinib · Drug: Liposomal mitoxantrone
Lisaftoclax oral with mandatory 6-day dose ramp-up (20mg→50mg→100mg→200mg→400mg→600mg QD), maintained at 600mg QD Days 1-21; standardized tumor lysis syndrome (TLS) prophylaxis (hydration + urate-lowering agents) and intensive serial TLS lab monitoring during dose escalation
Rituximab 375 mg/m² IV infusion on Cycle Day 0; premedication with paracetamol, diphenhydramine and corticosteroids for infusion reaction prophylaxis
Pirtobrutinib 200 mg oral QD, Days 1-21 of each cycle
Liposomal mitoxantrone 18 mg/m² IV infusion on Cycle Day 1
CR rate
Time frame: At the end of 4 cycles (each cycle is 21 days) of induction therapy
ORR
Time frame: At the end of 4-cycle(each cycle is 21 days) induction treatment period
DOR
Time frame: From the date of first confirmed CR or PR until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years.
PFS
Time frame: Up to 5 years
OS
Time frame: Up to 5 years
MRD Negative Rate
Time frame: At the end of 4 cycles (each cycle is 21 days) of induction therapy
Plan to share: Undecided
No publications or documents are linked to this record.
Start is estimated for Sep 2026; primary completion for Dec 2030, 51 months later.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Lisaftoclax
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