Comparing two treatment combinations for Hairy Cell Leukemia

A Randomized, Multi-Center, Phase II Study of Vemurafenib Plus Obinutuzumab vs. Cladribine Plus Rituximab in Patients With Previously Untreated Hairy Cell Leukemia (HCL)

This study is testing whether a new combination of drugs can work better and cause fewer side effects than the standard treatment for patients with Hairy Cell Leukemia who have a specific genetic mutation.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 86 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Memorial Sloan Kettering Cancer Center (other)
• Drugs / interventions: rituximab, obinutuzumab, chemotherapy
• Locations: 10 sites (Boston, Massachusetts and 9 other locations)
• Trial ID: NCT06561360 on ClinicalTrials.gov

What this trial studies

This study aims to compare the safety and effectiveness of vemurafenib combined with obinutuzumab against the standard treatment of cladribine combined with rituximab in patients with Hairy Cell Leukemia. Researchers will evaluate which treatment results in fewer side effects and better cancer cell elimination. The study focuses on patients with a specific genetic mutation (BRAF V600E) and will assess their response to these non-chemotherapy drugs versus traditional chemotherapy options.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed classical Hairy Cell Leukemia and the BRAF V600E mutation.

Not a fit: Patients who have previously received treatment for Hairy Cell Leukemia or do not have the BRAF V600E mutation may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a safer and more effective treatment option for patients with Hairy Cell Leukemia.

How similar studies have performed: Other studies have shown promise with similar non-chemotherapy approaches, suggesting potential for success in this trial.

Eligibility criteria

Inclusion Criteria:

* Patients must be ≥ 18 years of age
* Histologically confirmed classical HCL by the enrolling institution
* Presence of BRAF V600E mutation as confirmed by PCR, NGS or immunohistochemistry. If patient is known to have negative BRAF mutation, repeat testing is advisable as well as discussion with the main study principal investigator.
* Has not received any prior therapy for the disease
* Patients who meet the standard treatment initiation criteria, as defined by ANC ≤1.0, Hgb ≤ 10.0 or PLT ≤100K
* ECOG performance status of 0 - 2
* Acceptable pre-study organ function during screening as defined as:

  * Total bilirubin ≤ 1.5 times the upper limit of normal (ULN);
  * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5x ULN; and
  * Serum creatinine ≤ 1.5x ULN
* 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
* For women of childbearing potential, agreement to the use of two acceptable methods of contraception, including one barrier method, during the study and for 6 months after discontinuation of vemurafenib and cladribine, and 18 months after discontinuation of rituximab and obinutuzumab
* For men with female partners of childbearing potential, agreement to use a latex condom and to advise their female partner to use an additional method of contraception during the study and for 6 months after discontinuation of vemurafenib
* Negative serum pregnancy test within 7 days of commencement of treatment in women of childbearing potential

Exclusion Criteria:

* Have had previous treatment for HCL, including purine analogs, vemurafenib, rituximab, obinutuzumab, and other investigational agents. Previous treatment with transfusions and other supportive care such as G-CSF and erythropoietin are allowed.
* Known hypersensitivity to any of the study drugs.
* Patients with known long QT syndrome or uncorrectable electrolyte abnormalities
* Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis.
* Presence of positive test results for hepatitis B virus (HBV), hepatitis B surface antigen (HBsAg) or hepatitis C (HCV) antibody

  ° Patients with occult or prior HBV infection (defined as positive total hepatitis B core antibody \[HBcAb\] and negative HBsAg) may be included if HBV DNA is undetectable. These patients must be willing to undergo monthly DNA testing and take HBV viral prophylaxis such as entecavir.
* Known infection with HIV or human T-cell leukemia virus 1 (HTLV-1)
* Active uncontrolled infection, e.g. persistent bacteremia, supplemental oxygen or pressor supports, etc.
* Live vaccination within 28 days of randomization
* Patients with concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation or hormonal therapy, with the exception of squamous and basal cell carcinoma of the skin, in situ cervical cancer, adequately treated stage I/II cancer from which the patient is current in complete remission, or any other cancer from which the patient has been disease free for five years
* Malabsorption syndrome or other condition that precludes enteral route of administration
* Patients with HCL variant (as defined by absence of expression of CD25)
* Pregnant or lactating, or intending to become pregnant during the study

Where this trial is running

Boston, Massachusetts and 9 other locations

• Dana Farber Cancer Institute — Boston, Massachusetts, United States (NOT_YET_RECRUITING)
• Mayo Clinic Cancer Center — Rochester, Minnesota, United States (NOT_YET_RECRUITING)
• Memorial Sloan Kettering at Basking Ridge (All Protocol Activities) — Basking Ridge, New Jersey, United States (RECRUITING)
• Memorial Sloan Kettering Monmouth (Limited Protocol Activities) — Middletown, New Jersey, United States (RECRUITING)
• Memorial Sloan Kettering Bergen (Limited Protocol Activities) — Montvale, New Jersey, United States (RECRUITING)
• Memorial Sloan Kettering Cancer Commack - Suffolk (Limited Protocol Activities) — Commack, New York, United States (RECRUITING)
• Memorial Sloan Kettering Westchester (All Protocol Activities) — Harrison, New York, United States (RECRUITING)
• Memorial Sloan Kettering Cancer Center (All Protocol Activities) — New York, New York, United States (RECRUITING)
• Memorial Sloan Kettering Nassau (Limited Protocol Activities) — Uniondale, New York, United States (RECRUITING)
• Ohio State University — Columbus, Ohio, United States (RECRUITING)

Study contacts

• Principal investigator: Jae Park, MD — Memorial Sloan Kettering Cancer Center
• Study coordinator: Jae Park, MD

Conditions: Hairy Cell Leukemia, Vemurafenib, Obinutuzumab, Cladribine, Rituximab, 24-160