Clinical trial NCT06561360: A Study of Vemurafenib and Obinutuzumab Compared to Cladribine and Rituximab in People with Hairy Cell Leukemia (HCL)
Official title: A Randomized, Multi-Center, Phase II Study of Vemurafenib Plus Obinutuzumab Vs. Cladribine Plus Rituximab in Patients with Previously Untreated Hairy Cell Leukemia (HCL)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hairy Cell Leukemia
Keywords: Vemurafenib
Obinutuzumab
Cladribine
Rituximab
24-160
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2024-08-20
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized phase II multi-center, open-label, study of vemurafenib plus obinutuzumab (experimental arm) vs. cladribine plus rituximab (standard of care arm) in patients with previously untreated HCL.
Primary purpose: TREATMENT

Brief summary: The researchers are doing this study to compare the safety of vemurafenib in combination with obinutuzumab to the standard of approach of cladribine in combination with rituximab. The researchers will look at which treatment causes fewer or milder side effects. Researchers think vemurafenib and obinutuzumab (non-chemotherapy drugs) may cause fewer side effects compared with the usual approach of chemotherapy drugs. They will also compare the two approaches to see which approach is more effective at eliminating cancer cells.


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

Primary outcomes:
measure: incidences of ≥ grade 3 treatment-related toxicities
timeFrame: within 6 months of treatment
Secondary outcomes:
measure: complete remission
timeFrame: 2 years
measure: partial response
timeFrame: 2 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering at Basking Ridge (All Protocol Activities)
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen (Limited Protocol Activities)
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Cancer Commack - Suffolk (Limited Protocol Activities)
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester (All Protocol Activities)
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center (All Protocol Activities)
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau (Limited Protocol Activities)
state: New York
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Jae Park, MD
role: PRINCIPAL_INVESTIGATOR
References: