Trial Outcomes & Findings for BRAF Inhibitor, Vemurafenib, in Patients With Relapsed or Refractory Hairy Cell Leukemia (NCT NCT01711632)
NCT ID: NCT01711632
Last Updated: 2025-10-20
Results Overview
as assessed by overall response rates after three months of treatment in patients with relapsed or refractory HCL. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
COMPLETED
PHASE2
36 participants
3 months
2025-10-20
Participant Flow
Participant milestones
| Measure |
Vemurafenib
Eligible patients will receive vemurafenib at a dose of 960mg orally twice daily (b.i.d.) continuously in cycles of 4 weeks (28 days).
|
|---|---|
|
Overall Study
STARTED
|
36
|
|
Overall Study
COMPLETED
|
14
|
|
Overall Study
NOT COMPLETED
|
22
|
Reasons for withdrawal
| Measure |
Vemurafenib
Eligible patients will receive vemurafenib at a dose of 960mg orally twice daily (b.i.d.) continuously in cycles of 4 weeks (28 days).
|
|---|---|
|
Overall Study
Adverse Event
|
4
|
|
Overall Study
Death
|
3
|
|
Overall Study
Lost to Follow-up
|
3
|
|
Overall Study
Withdrawal by Subject
|
4
|
|
Overall Study
Progressive disease
|
2
|
|
Overall Study
No follow up required in re-treatment
|
3
|
Baseline Characteristics
BRAF Inhibitor, Vemurafenib, in Patients With Relapsed or Refractory Hairy Cell Leukemia
Baseline characteristics by cohort
| Measure |
Vemurafenib
n=36 Participants
Eligible patients will receive vemurafenib at a dose of 960mg orally twice daily (b.i.d.) continuously in cycles of 4 weeks (28 days).
|
|---|---|
|
Age, Continuous
|
60 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
30 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
35 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
33 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
36 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 3 monthsas assessed by overall response rates after three months of treatment in patients with relapsed or refractory HCL. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Outcome measures
| Measure |
Vemurafenib
n=36 Participants
Eligible patients will receive vemurafenib at a dose of 960mg orally twice daily (b.i.d.) continuously in cycles of 4 weeks (28 days).
|
|---|---|
|
Efficacy of Vemurafenib
Complete Response
|
10 Participants
|
|
Efficacy of Vemurafenib
Partial Response
|
14 Participants
|
|
Efficacy of Vemurafenib
No CR or PR
|
12 Participants
|
SECONDARY outcome
Timeframe: 2 yearsToxicity will be graded and recorded using the NCI Common Toxicology Criteria version 4.0.
Outcome measures
| Measure |
Vemurafenib
n=36 Participants
Eligible patients will receive vemurafenib at a dose of 960mg orally twice daily (b.i.d.) continuously in cycles of 4 weeks (28 days).
|
|---|---|
|
Toxicity (Safety and Tolerability)
Dose reduction to 480mg twice daily
|
10 Participants
|
|
Toxicity (Safety and Tolerability)
Dose reduction to 240mg twice daily
|
1 Participants
|
|
Toxicity (Safety and Tolerability)
Did not need a dose reduction
|
23 Participants
|
|
Toxicity (Safety and Tolerability)
Dose reduction to 720mg twice daily
|
2 Participants
|
SECONDARY outcome
Timeframe: 2 yearsPeripheral blood and/or bone marrow aspirate samples from pretreatment and post-treatment at specified time points will be assessed by Western Blot or by phospho-flow for the downstream targets of BRAF (MEK, pMEK, ERK, pERK) to assess the ontarget effect of the Vemurafenib. The droplet digital PCR assay was performed to quantify the concentration of molecules with mutated BRAF V600E DNA at baseline and again at 12 weeks of vermurafenib therapy.
Outcome measures
| Measure |
Vemurafenib
n=36 Participants
Eligible patients will receive vemurafenib at a dose of 960mg orally twice daily (b.i.d.) continuously in cycles of 4 weeks (28 days).
|
|---|---|
|
To Assess the Pharmacodynamics Change From Baseline
Pts with a decrease of the concentration of molecules with mutated BRAF V600E DNA at 12 wks
|
24 participants
|
|
To Assess the Pharmacodynamics Change From Baseline
Pts without decrease of the concentration of molecules with mutated BRAF V600E DNA at 12 wks
|
12 participants
|
SECONDARY outcome
Timeframe: 2 yearsReactivation of MAPK pathways: Increased expression of the other RAF isoforms CRAF and ARAF), and MAPK (MAPK8 or COT) will be analyzed by Western Blot and/or real-time PCR39,40. Secondary BRAF mutations (all 18 BRAF exons) and RAS mutations40 will be analyzed by bidirectional Sanger sequencing and by Raindance multiplex PCR and Illumina next generation sequencing, respectively. Activation of RTKs (i.e. PDGFRβ and IGF-IR) will be assessed by Western Blot. Cell Biosciences NanoPro 1000 technology will be used to examine quantitative signaling on the entire MAPK, PI3K and JAK-STAT pathways41.
Outcome measures
| Measure |
Vemurafenib
n=36 Participants
Eligible patients will receive vemurafenib at a dose of 960mg orally twice daily (b.i.d.) continuously in cycles of 4 weeks (28 days).
|
|---|---|
|
Evaluate Biomarkers of Resistance
Participants without KRAS mutations
|
35 Participants
|
|
Evaluate Biomarkers of Resistance
Participants with KRAS mutations
|
1 Participants
|
Adverse Events
Vemurafenib
Serious adverse events
| Measure |
Vemurafenib
n=36 participants at risk
Eligible patients will receive vemurafenib at a dose of 960mg orally twice daily (b.i.d.) continuously in cycles of 4 weeks (28 days).
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
2.8%
1/36 • 2 years
|
|
Immune system disorders
Anaphylaxis
|
2.8%
1/36 • 2 years
|
|
Blood and lymphatic system disorders
Anemia
|
2.8%
1/36 • 2 years
|
|
Cardiac disorders
Atrial fibrillation
|
2.8%
1/36 • 2 years
|
|
Investigations
Blood bilirubin increased
|
2.8%
1/36 • 2 years
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
13.9%
5/36 • 2 years
|
|
General disorders
Fever
|
8.3%
3/36 • 2 years
|
|
Gastrointestinal disorders
Gastrointestinal disorders, other
|
2.8%
1/36 • 2 years
|
|
Vascular disorders
Hematoma
|
2.8%
1/36 • 2 years
|
|
Infections and infestations
Lung infection
|
5.6%
2/36 • 2 years
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
2.8%
1/36 • 2 years
|
|
Gastrointestinal disorders
Rectal hemorrhage
|
2.8%
1/36 • 2 years
|
|
Skin and subcutaneous tissue disorders
Skin & subcutaneous tissue disorders, other
|
2.8%
1/36 • 2 years
|
|
Nervous system disorders
Syncope
|
2.8%
1/36 • 2 years
|
Other adverse events
| Measure |
Vemurafenib
n=36 participants at risk
Eligible patients will receive vemurafenib at a dose of 960mg orally twice daily (b.i.d.) continuously in cycles of 4 weeks (28 days).
|
|---|---|
|
Metabolism and nutrition disorders
Hyperglycemia
|
58.3%
21/36 • 2 years
|
|
Blood and lymphatic system disorders
Platelet count decreased
|
58.3%
21/36 • 2 years
|
|
Blood and lymphatic system disorders
Anemia
|
55.6%
20/36 • 2 years
|
|
Investigations
Neutrophil count decreased
|
52.8%
19/36 • 2 years
|
|
Investigations
White blood cell decreased
|
52.8%
19/36 • 2 years
|
|
Investigations
Lymphocyte count decreased
|
47.2%
17/36 • 2 years
|
|
Investigations
Blood bilirubin increased
|
38.9%
14/36 • 2 years
|
|
Investigations
Alkaline phosphatase increased
|
33.3%
12/36 • 2 years
|
|
Investigations
Alanine aminotransferase increased
|
30.6%
11/36 • 2 years
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
27.8%
10/36 • 2 years
|
|
Investigations
Aspartate aminotransferase increased
|
25.0%
9/36 • 2 years
|
|
Investigations
Creatinine increased
|
22.2%
8/36 • 2 years
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
22.2%
8/36 • 2 years
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
22.2%
8/36 • 2 years
|
|
Metabolism and nutrition disorders
Hypernatremia
|
19.4%
7/36 • 2 years
|
|
Investigations
INR increased
|
19.4%
7/36 • 2 years
|
|
Metabolism and nutrition disorders
Hyponatremia
|
16.7%
6/36 • 2 years
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
13.9%
5/36 • 2 years
|
|
Investigations
Activated partial thromboplastin time prolonged
|
11.1%
4/36 • 2 years
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
8.3%
3/36 • 2 years
|
|
Metabolism and nutrition disorders
Hypokalemia
|
8.3%
3/36 • 2 years
|
|
Investigations
Fibrinogen decreased
|
2.8%
1/36 • 2 years
|
|
Investigations
Hemoglobin increased
|
2.8%
1/36 • 2 years
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
2.8%
1/36 • 2 years
|
Additional Information
Dr. Jae Park, MD
Memorial Sloan Kettering Cancer Center
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place