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Testing Tovorafenib Plus Rituximab for Hairy Cell Leukemia

This study is testing the combination of two anti-cancer drugs, tovorafenib and rituximab, for patients with hairy cell leukemia. This includes patients whose cancer has returned (recurrent), hasn't responded to previous treatments (refractory), or those who haven't been treated yet. Tovorafenib works by blocking certain proteins from a mutated BRAF gene, which can stop cancer cells from growing. Rituximab targets a protein called CD20 on certain white blood cells and cancer cells. The study aims to see how safe and effective this combination is, and for some patients, it will compare it to a standard treatment of cladribine and rituximab. To join, you must have a confirmed diagnosis of classical hairy cell leukemia with a specific gene change called BRAF V600E. The study is currently unclear on its recruitment status and plans to enroll 84 participants. Success will be measured by how well the treatment reduces the cancer and its side effects.

Study design
This is a Phase I/II interventional study that aims to enroll 84 participants. It will evaluate the safety and effectiveness of the drug combination.
What's involved
You would undergo blood sample and buccal swab collection, bone marrow aspiration and biopsy, and CT scans. You would also receive cladribine intravenously.
Compensation
Not stated in the trial record.
Follow-up
The study measures adverse events during cycles 1-3 (28 days each) and minimal residual disease at the completion of treatment.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT06965114

Testing the Combination of Anti-cancer Drugs, Tovorafenib Plus Rituximab, in Patients With Hairy Cell Leukemia

Recruiting
PHASE1Ages 18+InterventionalTreatment
National Cancer Institute (NCI)
~84 participants
Updated 2026-07-31 on ClinicalTrials.gov
What's tested:Biospecimen CollectionBone Marrow AspirationBone Marrow BiopsyCladribineComputed TomographyRituximab

At a glance

Recruiting sites
4 of 4 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Incidence of adverse events (Phase 1)
Measured over During cycles 1-3 (cycle length = 28 days)
+1 more outcome measured

Conditions

Hairy Cell Leukemia
Recurrent Hairy Cell Leukemia
Refractory Hairy Cell Leukemia

Explore related trials

Hairy Cell LeukemiaBRAF Gene

Where it's being run

4 sites across 4 states
Maryland1
Ohio1
Pennsylvania1
Virginia1

Study leadership

  • Seema A Bhat · PRINCIPAL_INVESTIGATOR · Ohio State University Comprehensive Cancer Center LAO

Who to contact

Site Public Contact
800-411-1222
Do you actually qualify for this trial?

Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.

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Eligibility criteria

Inclusion

Patients must have histologically or cytologically confirmed diagnosis of classical hairy cell leukemia (HCL), including demonstration of BRAF V600E mutation by immunohistochemistry, molecular diagnostic testing, or polymerase chain reaction (PCR)
PHASE 1 ONLY: Prior therapy with at least one purine nucleoside analog-containing regimen (fludarabine, pentostatin, or cladribine) unless contraindicated. Prior vemurafenib alone is allowed in the relapsed/refractory cohort
PHASE 2 ONLY: No prior HCL-directed treatment for front-line cohort. The design of this cohort is such that the patients will need to be treatment naïve
Age ≥ 18 years. Because no dosing or adverse event (AE) data are currently available on the use of tovorafenib (DAY101) or cladribine in combination with rituximab in patients \< 18 years of age, children are excluded from this study
Patients must meet indications for treatment of cHCL:
Absolute neutrophil count \< 1,000/mcL
Platelets \< 100,000/mcL
Hemoglobin \< 10 g/dL
Recurrent infections
Symptomatic and/or progressive extramedullary disease including lymph nodes and bone lesions
Progressive or symptomatic splenomegaly or hepatomegaly
Disease-related constitutional symptoms consisting of unexplained weight loss exceeding 10% body weight during the preceding 6 months, Cancer Therapy Evaluation Program (CTEP) active version of the Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or 3 fatigue, and/or fever \> 100.5 F or night sweats for \> 2 weeks without evidence of active infection
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%); ECOG performance status \> 2 (Karnofsky \< 60%) will be allowed if considered due to HCL
Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x institutional ULN (unless related to Gilbert's disease or HCL; patients with documented Gilbert's disease may be enrolled with sponsor approval provided total bilirubin is ≤ 2.0 x ULN)
Creatinine clearance (ClCr) ≥ 30 mL/min
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load for \> 6 months
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
Electrocardiogram (ECG) without evidence of clinically significant ventricular arrhythmias or ischemia as determined by the investigator and a rate-corrected QT interval (QTc, Bazett's formula) of \< 480 msec
The effects of tovorafenib (DAY101), cladribine, and rituximab on the developing human fetus are unknown. For this reason and because BRAF kinase inhibitor agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential (WOCBP) and men must agree to use two forms of adequate contraception (including a highly effective birth control method in addition to a barrier method) during treatment prior to study entry and for the duration of study treatment participation and 12 months after the last dose of the study medication
WOCBP should use effective non-hormonal contraception during treatment and for 12 months after the last dose of the study medication. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. For male patients with a female partner of childbearing potential, a condom should be used for contraception in addition to one of the highly effective contraception methods prior to the study, for the duration of study treatment, and 12 months after the last dose of the study medication. Male patients must not father a child or donate sperm while participating in this study
Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives (LARs) may sign and give informed consent on behalf of study participants

Exclusion

Central nervous system (CNS) involvement with HCL is very rare, and therefore the biology of the disease in patients with CNS involvement may not be representative of the disease under study as a whole. Patients with treated brain metastases are eligible if follow-up brain imaging after CNS-directed therapy shows no evidence of progression
Patients with HCL who are BRAF V600E mutation negative and those with the variant HCL
Patients with platelets \< 50,000/mCL
Patients on warfarin and direct oral anticoagulants (due to risk of bleeding)
Patients who have not recovered from AEs as a result of prior anti-cancer therapy (i.e., have residual toxicities \> grade 1), with the exception of alopecia
Patients who are receiving any other investigational agents
Patients who are receiving strong CYP2C8 inhibitors, inducers, and breast cancer resistance protein (BCRP) substrates with narrow therapeutic index
Patients who are pregnant, breastfeeding, and/or unwilling to use adequate contraception during the study period and for 12 months after completion of the study
Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to tovorafenib (DAY101) or other agents used in the study, including those with a previous history of severe infusion-related reaction (anaphylaxis) with rituximab administration
Patients with known hypersensitivity to any of the study drugs
Patients with an inability to swallow oral medications or with gastrointestinal impairment
Live or live-attenuated vaccines within 28 days of randomization
Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
Pregnant women are excluded from this study because tovorafenib (DAY101) is a BRAF kinase inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with tovorafenib (DAY101), breastfeeding should be discontinued if the mother is treated with tovorafenib (DAY101). These potential risks may also apply to other agents used in this study

What this trial measures

  • Incidence of adverse events (Phase 1)During cycles 1-3 (cycle length = 28 days)

    Adverse events (AEs) will be documented and summarized by type, grade, severity, and attribution using the Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 criteria for non-hematologic toxicities and table of criteria for hematologic toxicities. In addition, the number of treatment cycles received and reasons for going off treatment will be summarized to assess treatment tolerability. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.

  • Minimal residual disease negative complete remission (MRD [-] CR) rate (Phase 2)At completion of tovorafenib plus rituximab treatment versus cladribine plus rituximab

    Will be calculated as the proportion of patients who achieve MRD (-) CR to therapy divided by the total number of patients for each treatment arm. All randomized patients or evaluable patients will be included in calculating the rate of MRD (-) CR for the study along with corresponding 95% binomial confidence intervals (CIs) (assuming that the number of patients who respond is binomially distributed). The MRD (-) CR rate will be compared between the untreated classical hairy cell leukemia (cHCL) patients with tovorafenib plus rituximab treatment and the patients with cladribine plus rituximab using the chi-square test or Fisher's exact test.