Description:
This is a multi-center, open label, single arm, phase II trial of the oral BRAF inhibitor,
vemurafenib, plus obinutuzumab in patients with previously untreated HCL. A Simon mini-max
two-stage design will be employed to assess the efficacy of the combination treatment of
vemurafenib and obinutuzumab. In the first stage of the protocol, 9 patients will be treated.
If fewer than 6 CRs are seen among the first 9 patients, the study will be closed for lack of
efficacy. If at least 7 patients respond to the treatment, then an additional 19 patients
will be accrued to the second stage, for a total of 28 patients.
Eligible patients will receive vemurafenib at a dose of 960mg orally twice daily (b.i.d.)
continuously in cycles of 4 weeks (28 days) for a total of 4 cycles.
Obinutuzumab will be administered concomitantly with vemurafenib starting at cycle 2 of
treatment in cycles of 4 weeks. Obinutuzumab infusions will be administered at 1000mg per day
on days 1, 8 and 15 during the cycle 2 and 1000mg per day every 4 weeks during the cycle 3
and 4 of treatment. After the completion of the treatment (i.e. after 4 cycles), a bone
marrow aspirate and biopsy will be performed for assessment of response and evaluation of
minimal residual disease (MRD). In case of certain defined toxicities, dose reductions of
vemurafenib by 50% (480mg b.i.d.) or interruptions of up to 15 days are permitted. If
additional dose reduction is required, vemurafenib may be reduced to 240mg oral b.i.d.
Title
- Brief Title: A Phase II Study of the BRAF Inhibitor, Vemurafenib, Plus Obinutuzumab in Patients With Previously Untreated Classical Hairy Cell Leukemia
- Official Title: A Phase II Study of the BRAF Inhibitor, Vemurafenib, Plus Obinutuzumab in Patients With Previously Untreated Classical Hairy Cell Leukemia
Clinical Trial IDs
- ORG STUDY ID:
17-513
- NCT ID:
NCT03410875
Conditions
- Hairy Cell Leukemia
- Leukemia
- Leukemia, Hairy Cell
Interventions
| Drug | Synonyms | Arms |
|---|
| Vemurafenib | | Untreated Hairy Cell Leukemia |
| Obinutuzumab | | Untreated Hairy Cell Leukemia |
Purpose
This is a multi-center, open label, single arm, phase II trial of the oral BRAF inhibitor,
vemurafenib, plus obinutuzumab in patients with previously untreated HCL. A Simon mini-max
two-stage design will be employed to assess the efficacy of the combination treatment of
vemurafenib and obinutuzumab. In the first stage of the protocol, 9 patients will be treated.
If fewer than 6 CRs are seen among the first 9 patients, the study will be closed for lack of
efficacy. If at least 7 patients respond to the treatment, then an additional 19 patients
will be accrued to the second stage, for a total of 28 patients.
Eligible patients will receive vemurafenib at a dose of 960mg orally twice daily (b.i.d.)
continuously in cycles of 4 weeks (28 days) for a total of 4 cycles.
Obinutuzumab will be administered concomitantly with vemurafenib starting at cycle 2 of
treatment in cycles of 4 weeks. Obinutuzumab infusions will be administered at 1000mg per day
on days 1, 8 and 15 during the cycle 2 and 1000mg per day every 4 weeks during the cycle 3
and 4 of treatment. After the completion of the treatment (i.e. after 4 cycles), a bone
marrow aspirate and biopsy will be performed for assessment of response and evaluation of
minimal residual disease (MRD). In case of certain defined toxicities, dose reductions of
vemurafenib by 50% (480mg b.i.d.) or interruptions of up to 15 days are permitted. If
additional dose reduction is required, vemurafenib may be reduced to 240mg oral b.i.d.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Untreated Hairy Cell Leukemia | Experimental | Participants with HCL with no prior treatment for the disease | |
Eligibility Criteria
Inclusion Criteria:
- Patients must be >/= 18 years of age
- Histologically confirmed classical HCL by the enrolling institution
- 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
- 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 (QT 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
- 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 with 7 days of commencement of treatment in women of
childbearing potential
Exclusion Criteria:
- Have had previous treatment for HCL, including purine analogs, rituximab, 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
- Clinically significant history of liver disease, including viral or other hepatitis,
current alcohol abuse, or cirrhosis.
- Patients with uncorrectable electrolyte abnormalities with potassium (K) >ULN (upper
limit of normal).
- Patients with any active and uncontrolled infections (such as bacterial, fungal, and
new or reactivated viral infections)
- Presence of positive test results for hepatitis B virus (HBV), hepatitis B surface
antigen (HBsAg) or hepatitis C (HCV) antibody.
- Patients who are positive for HCV antibody must be negative for HCV by polymerase
chain reaction (PCR) to be eligible for study participation.
- 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.
- Known infection with HIV or human T-cell leukemia virus 1 (HTLV-1)
- Invasive malignancy that require active systemic chemotherapy or biologics that may
cause significant drug-drug interaction with either vemurafenib or obinutuzumab
- 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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Efficacy of vemurafenib in combination with obinutuzumab |
| Time Frame: | 16 weeks |
| Safety Issue: | |
| Description: | Efficacy as assessed by complete response (CR) rates of participants |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Memorial Sloan Kettering Cancer Center |
Trial Keywords
- Leukemia
- Hairy Cell Leukemia
- BRAF
- vemurafenib
- obinutuzumab
- Memorial Sloan Kettering Cancer Center
- 17-513
Last Updated
June 15, 2021
