Trial Title:
A Study of Vemurafenib and Obinutuzumab Compared to Cladribine and Rituximab in People with Hairy Cell Leukemia (HCL)
NCT ID:
NCT06561360
Condition:
Hairy Cell Leukemia
Conditions: Official terms:
Leukemia
Leukemia, Hairy Cell
Rituximab
Obinutuzumab
Vemurafenib
Cladribine
Conditions: Keywords:
Vemurafenib
Obinutuzumab
Cladribine
Rituximab
24-160
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
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
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Vemurafenib
Description:
Vemurafenib orally twice daily (b.i.d.) continuously in cycles of 4 weeks (28 days) for a
total of 4 cycles.
Arm group label:
Vemurafenib plus Obinutuzumab
Intervention type:
Drug
Intervention name:
Obinutuzumab
Description:
Obinutuzumab will be administered concomitantly with vemurafenib starting at cycle 2 of
treatment in cycles of 4 weeks.
Arm group label:
Vemurafenib plus Obinutuzumab
Intervention type:
Drug
Intervention name:
Cladribine
Description:
Cladribine IV on days 1-5 concurrently with rituximab.
Arm group label:
Standard treatment of Cladribine plus Rituximab
Intervention type:
Drug
Intervention name:
Rituximab
Description:
Rituximab on days 1-5 concurrently with rituximab.
Arm group label:
Standard treatment of Cladribine plus Rituximab
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.
Criteria for 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Dana Farber Cancer Institute
Address:
City:
Boston
Zip:
02115
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Eric Winer, MD
Phone:
(617) 632-6876
Facility:
Name:
Mayo Clinic Cancer Center
Address:
City:
Rochester
Zip:
55905
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Sameer Parikh, M.B.B.S.
Phone:
507-218-0772
Facility:
Name:
Memorial Sloan Kettering at Basking Ridge (All Protocol Activities)
Address:
City:
Basking Ridge
Zip:
07920
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jae Park, MD
Phone:
646-608-3743
Facility:
Name:
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
Address:
City:
Middletown
Zip:
07748
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jae Park, MD
Phone:
646-608-3743
Facility:
Name:
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Address:
City:
Montvale
Zip:
07645
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jae Park, MD
Phone:
646-608-3743
Facility:
Name:
Memorial Sloan Kettering Cancer Commack - Suffolk (Limited Protocol Activities)
Address:
City:
Commack
Zip:
11725
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jae Park, MD
Phone:
646-608-3743
Facility:
Name:
Memorial Sloan Kettering Westchester (All Protocol Activities)
Address:
City:
Harrison
Zip:
10604
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jae Park, MD
Phone:
646-608-3743
Facility:
Name:
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jae Park, MD
Phone:
646-608-3743
Facility:
Name:
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
Address:
City:
Uniondale
Zip:
11553
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jae Park, MD
Phone:
646-608-3743
Facility:
Name:
Ohio State University
Address:
City:
Columbus
Zip:
43210
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Michael Grever, MD
Phone:
614-293-3196
Contact backup:
Last name:
Michael Grever, MD
Start date:
September 9, 2024
Completion date:
September 9, 2027
Lead sponsor:
Agency:
Memorial Sloan Kettering Cancer Center
Agency class:
Other
Collaborator:
Agency:
Genentech, Inc.
Agency class:
Industry
Source:
Memorial Sloan Kettering Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06561360
http://www.mskcc.org/mskcc/html/44.cfm
