Hairy Cell Leukemia
Conditions
Keywords
Vemurafenib, Obinutuzumab, Cladribine, Rituximab, 24-160
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.
Interventions
DRUGVemurafenib
Vemurafenib orally twice daily (b.i.d.) continuously in cycles of 4 weeks (28 days) for a total of 4 cycles.
DRUGObinutuzumab
Obinutuzumab will be administered concomitantly with vemurafenib starting at cycle 2 of treatment in cycles of 4 weeks.
DRUGCladribine
Cladribine IV on days 1-5 concurrently with rituximab.
DRUGRituximab
Rituximab on days 1-5 concurrently with rituximab.
Sponsors
Memorial Sloan Kettering Cancer Center
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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), except in patients with known Gilbert's syndrome who may be enrolled if direct bilirubin ≤ 3 x 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| incidences of ≥ grade 3 treatment-related toxicities | within 6 months of treatment | per CTCAE v5.0 within first 6 months from the start of the treatment to account delayed toxicities of the treatments |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| complete remission | 2 years | Response will be determined by the Consensus Resolution response criteria. Complete response (CR) * A morphological absence of hairy cells in the blood and bone marrow * A normalization of any organomegaly and cytopenias |
| partial response | 2 years | Partial response (PR) °A normalization of cytopenias °≥50% reduction in organomegaly and bone marrow hairy cells. |
Countries
United States
Contacts
CONTACTJae Park, MD
CONTACTMark Geyer, MD
PRINCIPAL_INVESTIGATORJae Park, MD
Memorial Sloan Kettering Cancer Center
Outcome results
None listed