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

Conditions

• Hairy Cell Leukemia
• Recurrent Hairy Cell Leukemia
• Refractory Hairy Cell Leukemia

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Biospecimen Collection — PROCEDURE
  Undergo blood sample and buccal swab collection
• Bone Marrow Aspiration — PROCEDURE
  Undergo bone marrow biopsy and aspiration
• Bone Marrow Biopsy — PROCEDURE
  Undergo bone marrow biopsy and aspiration
• Cladribine — DRUG
  Given IV
• Computed Tomography — PROCEDURE
  Undergo CT
• Rituximab — BIOLOGICAL
  Given IV
• Tovorafenib — DRUG
  Given PO

Study Details

This phase I/II trial tests the safety, side effects, and effectiveness of tovorafenib in combination with rituximab in patients with classical hairy cell leukemia (cHCL) that has come back after a period of improvement (recurrent) or that has not responded to previous treatment (refractory) and compares the effect of tovorafenib and rituximab to current standard treatment of cladribine and rituximab in cHCL patients that have not yet received treatment. Tovorafenib blocks certain proteins made by the mutated BRAF gene, which may help keep cancer cells from growing. It is a type of kinase inhibitor. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Cladribine damages the cell's deoxyribonucleic acid and may kill cancer cells. It is a type of antimetabolite. Giving tovorafenib in combination with rituximab may be safe and tolerable and more effective than cladribine with rituximab in treating patients with untreated, recurrent or refractory cHCL.

Key Dates

Start date

May 29, 2026

Status verified

May 2026

Primary completion

Mar 1, 2030

Completion

Mar 1, 2030

Study Design

Enrollment

84 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Phase 1 (tovorafenib, rituximab)
  Patients receive tovorafenib PO QW for up to 16 weeks and rituximab IV QW on weeks 5-9 and 11, 13, and 15 in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, CT as clinically indicated, and bone marrow biopsy and aspiration throughout the study. Additionally, patients undergo buccal swab collection pre-study.
• Active Comparator: Phase 2 Arm A (cladribine, rituximab)
  Patients receive cladribine IV over 2 hours on days 1-5 of cycle 1 and rituximab IV on days 1, 8, 15, and 22 of cycles 2 and 3. Cycles repeat every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, CT as clinically indicated, and bone marrow biopsy and aspiration throughout the study.
• Experimental: Phase 2 Arm B (tovorafenib, rituximab)
  Patients receive tovorafenib PO on days 1, 8, 15, and 22 of each cycle and rituximab IV on days 1, 8, 15, and 22 of cycle 2 and on days 1 and 15 of cycles 3 and 4. Cycles repeat every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, CT as clinically indicated, and bone marrow biopsy and aspiration throughout the study.

Primary Outcome Measure

Incidence of adverse events (Phase 1) [ Time Frame: During cycles 1-3 (cycle length = 28 days) ]

Locations (4)

Find similar trials in Bethesda, MD

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