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Venetoclax

Patients receive venetoclax PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 19 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI and blood sample collection throughout the study. Patients may undergo bone marrow biopsy and/or aspiration on study.

Biospecimen Collection

Bone Marrow Aspiration

Bone Marrow Biopsy

Computed Tomography

Magnetic Resonance Imaging

Robert J Kreitman

This phase II trial tests how well venetoclax works in treating patients with hairy cell leukemia that has come back after a period of improvement (relapsed). Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival.

PRIMARY OBJECTIVE:

I. To determine the objective response rate (ORR) of venetoclax.

SECONDARY OBJECTIVES:

I. To determine the complete remission (CR) and minimal residual disease (MRD)-negative CR rates of venetoclax in relapsed hairy cell leukemia/hairy cell leukemia variant (HCL/HCLv).

II. To determine the rates of MRD-negative by blood flow cytometry with venetoclax.

III. To determine the safety of venetoclax in relapsed HCL/HCLv. IV. To determine the response and CR duration and MRD-negative survival in relapsed HCL/HCLv receiving venetoclax.

EXPLORATORY OBJECTIVES:

I. To correlate response to TP53 mutations and other mutations, particularly for BRAF wild-type (WT) relapsed HCL/HCLv.

II. To perform whole exome sequencing (WES) of relapsed HCL/HCLv samples to look for mutations, to correlate with response.

OUTLINE:

Patients receive venetoclax orally (PO) once daily (QD) on days 1-28 of each cycle. Treatment repeats every 28 days for up to 19 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) and blood sample collection throughout the study. Patients may undergo bone marrow biopsy and/or aspiration on study.

After completion of study treatment, patients are followed up at 30 days.

Venetoclax for the Treatment of Patients With Relapsed Hairy Cell Leukemia

A Phase 2 Study of Venetoclax in Relapsed Classic or Variant Hairy Cell Leukemia

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Will correlate response to TP53 mutations and other mutations.

Will perform whole exome sequencing of relapsed HCL/HCLv samples to look for mutations, to correlate with response.

Will be determined with 95% confidence intervals for each group.

CR will be defined as resolution of cytopenias with neutrophils \> 1.5/nL, platelets \> 100/nL, and hemoglobin \> 11g/dL at least 4 weeks from last transfusion or growth factor, resolution of splenomegaly by exam or by spleen size \< 17 cm by imaging, resolution of hairy cell leukemia (HCL)/hairy cell leukemia variant (HCLv)-related lymphadenopathy/masses to \< 2cm in short axis (\< 0.5 cm in short axis in the central nervous system \[CNS\]), and absence of morphological evidence of HCL/HCLv in the blood and bone marrow.

Defined as meeting the criteria for CR plus absence of HCL/HCLv cells in the bone marrow aspirate and blood by flow cytometry, and negative immunochemistry of the bone marrow biopsy. Positive IHC involves B-cells \> T-cells and most of the B-cells being consistent with HCL. Patients with CNS disease who achieve CR with positive cerebrospinal fluid flow cytometry will be considered CR with MRD.

Will determine the rates of MRD-negative by blood flow cytometry.

Spots Global Cancer Trial Database for recurrent hairy cell leukemia variant