CancerPhase 1NCT02973399
Efficacy and Safety of SNX-5422 Added to an Established Dose of Ibrutinib in CLL
A Phase 1 study testing SNX-5422 plus ibrutinib in people with Cancer, run by Esanex Inc. at 2 sites in United States.
Trial summary
SNX-5422 is a prodrug of SNX-2112, a potent, highly selective, small molecule inhibitor of the molecular chaperone heat shock protein 90 (HSP90). Hsp90 inhibitors may overcome ibrutinib resistance in Mantle cell lymphomas and this study will investigate whether the addition of SNX-5422 to an established dose of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer
- What is being tested?
- SNX-5422 plus ibrutinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 2 sitesUnited States
- Study dates
- 7 Feb 2017to 4 Feb 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or non-pregnant, non-breastfeeding females 18 years-of-age or older
- A diagnosis of CLL as defined by IWCLL 2008 criteria and currently on treatment with ibrutinib for at least 18 months with residual disease and without evidence of disease progression.
- No more than 4 prior lines of anti leukemia therapy (not including ibrutinib)
- Life expectancy of at least 9 months
- Karnofsky performance score 70
- Adequate baseline laboratory assessments
Show all 9Show fewer
- Signed informed consent form
- Recovered from toxicities of previous anticancer therapy to CTCAE Grade ≤ 1
- Subjects with reproductive capability must agree to practice adequate contraception methods.
Who cannot join
- Subjects experiencing toxicity with ibrutinib
- Prior treatment with any Hsp90 inhibitor.
- Major surgery or significant traumatic injury within 4 weeks of starting study treatment.
- Conventional chemotherapy or radiation within 4 weeks.
- The need for treatment with medications with clinically-relevant metabolism by the cytochrome P450 (CYP) 3A4 isoenzyme within 3 hours before or after administration of SNX-5422
- Screening ECG QTc interval 470 msec for females, 450 msec for males.
Show all 16Show fewer
- At increased risk for developing prolonged QT interval unless corrected to within normal limits prior to first dose of SNX-5422
- Patients with chronic diarrhea or with Grade 2 or greater diarrhea despite appropriate medical management.
- Gastrointestinal diseases or conditions that could affect drug absorption or could alter the assessment of safety
- History of documented adrenal dysfunction not due to malignancy.
- History of chronic liver disease.
- Active hepatitis A or B.
- Current alcohol dependence or drug abuse.
- Use of an investigational treatment (except for ibrutinib) from 30 days prior to the first dose
- Glaucoma, retinitis pigmentosa, macular degeneration, or any retinal changes detected by ophthalmological examination that are considered clinically important by examiner.
- Psychological or social reasons that would hinder or prevent compliance with the requirements of the protocol or compromise the informed consent process.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Wexner Medical Center, Ohio State University
Columbus, Ohio, 43210
Weill Cornell Medical College
New York, New York, 10065
About this study
Official title: A Phase 1, Open-label Study of SNX-5422 Added to Ibrutinib in Chronic Lymphocytic Leukemia Subjects With Residual Disease
SNX-5422 is a prodrug of SNX-2112, a potent, highly selective, small molecule inhibitor of the molecular chaperone heat shock protein 90 (HSP90). Hsp90 inhibitors may overcome ibrutinib resistance in Mantle cell lymphomas and this study will investigate whether the addition of SNX-5422 to an established dose of ibrutinib will provide clinical response in subjects who have residual disease, but have not progressed on ibrutinib after 18 months of monotherapy, and/or prevents or delays disease progression of subjects with CLL.
Read the detailed description
Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in adults and is not considered curable outside of allogeneic stem cell transplantation. Significant advances have been made in the therapy, notably with the introduction of the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib.
While response to ibrutinib has been high with therapy well-tolerated overall, some patients have relapsed while others have been taken off therapy for toxicity or other reasons. In addition, although remissions are durable in many patients, very few patients achieve a complete response (CR), and minimal residual disease (MRD) negativity on single agent ibrutinib has not been reported. Since it is known that for chemoimmunotherapy as well as targeted therapies such as venetoclax that attainment of a CR is associated with longer progression free survival (PFS), it is likely that deepening responses associated with ibrutinib will result in more durable remissions.
Relapse in CLL can be mediated by at least two separate mechanisms. One is by mutations in BTK, the other is through a variety of mutations in the immediate downstream target of BTK, PLCγ2. SNX-5422 is a prodrug of SNX-2112, a potent, highly selective, small molecule inhibitor of the molecular chaperone heat shock protein 90 (HSP90). Hsp90 inhibitors may overcome ibrutinib resistance in Mantle cell lymphomas and this study will investigate whether the addition of SNX-5422 to an established dose of ibrutinib will provide clinical response in subjects who have residual disease, but have not progressed on ibrutinib after 18 months of monotherapy.
Subjects will receive SNX-5422 (56 mg/m2) in the morning once every other day for 21 days (11 doses), followed by a 7-day drug-free period. Subjects will continue to receive daily oral ibrutinib at their established dose level in the afternoon
- Conditions
- Cancer
- Being tested
- SNX-5422 plus ibrutinib
- Keywords
- CLL, Leukemia, Chronic Lymphocytic, Hsp90, Ibrutinib
- Medical subject headings
- Neoplasms, Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SNX-5422 plus ibrutinibDrug
Also called Imbruvica
SNX-5422 capsule(s) dosed every other day for 21 days out of a 28-day treatment cycle to a total dose of 56 mg/m2 SNX-5422. Subjects will self-administer daily oral ibrutinib in the afternoon at least 8 hours apart from SNX-5422 for 28 days of each cycle.
| Study group | Role | What they receive |
|---|---|---|
| SNX-5422 plus ibrutinib | Experimental | Open-label administration of SNX-5422 capsules dosed in the morning once every other day for 21 days (11 doses) followed by a 7 day drug free period and daily with the established ibrutinib dose for 28 days of a 28-days cycle. Subjects will repeat the 28-day schedule for 2 cycles after a CR or until the cancer progresses or the subject is unable to tolerate the therapy Receives: Drug: SNX-5422 plus ibrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of the combination of SNX-5422 and ibrutinib
Proportion of subjects obtaining a complete response at the end of 6 SNX-5422 treatment cycles
Measured: 6 months
Secondary outcomes (4)
Number of subjects reporting adverse events
Frequency and severity of adverse events
Measured: Day 28 of each 4 week cycle from randomization up to 52 weeks
Complete response at 12 months
Proportion of subjects obtaining a complete response at the end of 6 SNX-5422 treatment cycles
Measured: 12 months
Improved Clinical Status
Proportion of subjects obtaining improvement in clinical status (i.e., Stable Disease becoming Partial Response) at the end of 6 SNX-5422 treatment cycles
Measured: 6 months
Progression free survival of patients receiving ibrutinib plus SNX-5422
Elapsed time for each subject from randomization to continued survival up to 52 weeks
Measured: Up to 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2016 (estimated)
- Study start7 Feb 2017
- Primary completion4 Dec 2018
- Study completion4 Feb 2019
Why it stopped: Low recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Esanex Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02973399
- Sponsor's protocol ID
- SNX-5422-CLN1-012
- Status last verified
- Feb 2019
- First submitted
- 22 Nov 2016
- Last updated
- 22 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-label Study of SNX-5422 Added to Ibrutinib in Chronic Lymphocytic Leukemia Subjects With Residual Disease
- ClinicalTrials.gov ID
- NCT02973399
- Acronym / sponsor ID
- SNX-5422-CLN1-012
- Conditions
- Cancer
- Keywords
- CLL, Leukemia, Chronic Lymphocytic, Hsp90, Ibrutinib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low recruitment
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Esanex Inc.Industry (pharma, biotech, devices)
- Study start
- 7 Feb 2017 (actual)
- Primary completion
- 4 Dec 2018 (actual)
- Study completion
- 4 Feb 2019 (actual)
- First posted
- 25 Nov 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
SNX-5422 is a prodrug of SNX-2112, a potent, highly selective, small molecule inhibitor of the molecular chaperone heat shock protein 90 (HSP90). Hsp90 inhibitors may overcome ibrutinib resistance in Mantle cell lymphomas and this study will investigate whether the addition of SNX-5422 to an established dose of ibrutinib will provide clinical response in subjects who have residual disease, but have not progressed on ibrutinib after 18 months of monotherapy, and/or prevents or delays disease progression of subjects with CLL.
Detailed description
Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in adults and is not considered curable outside of allogeneic stem cell transplantation. Significant advances have been made in the therapy, notably with the introduction of the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib.
While response to ibrutinib has been high with therapy well-tolerated overall, some patients have relapsed while others have been taken off therapy for toxicity or other reasons. In addition, although remissions are durable in many patients, very few patients achieve a complete response (CR), and minimal residual disease (MRD) negativity on single agent ibrutinib has not been reported. Since it is known that for chemoimmunotherapy as well as targeted therapies such as venetoclax that attainment of a CR is associated with longer progression free survival (PFS), it is likely that deepening responses associated with ibrutinib will result in more durable remissions.
Relapse in CLL can be mediated by at least two separate mechanisms. One is by mutations in BTK, the other is through a variety of mutations in the immediate downstream target of BTK, PLCγ2. SNX-5422 is a prodrug of SNX-2112, a potent, highly selective, small molecule inhibitor of the molecular chaperone heat shock protein 90 (HSP90). Hsp90 inhibitors may overcome ibrutinib resistance in Mantle cell lymphomas and this study will investigate whether the addition of SNX-5422 to an established dose of ibrutinib will provide clinical response in subjects who have residual disease, but have not progressed on ibrutinib after 18 months of monotherapy.
Subjects will receive SNX-5422 (56 mg/m2) in the morning once every other day for 21 days (11 doses), followed by a 7-day drug-free period. Subjects will continue to receive daily oral ibrutinib at their established dose level in the afternoon
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SNX-5422 plus ibrutinib | Experimental | Drug: SNX-5422 plus ibrutinibOpen-label administration of SNX-5422 capsules dosed in the morning once every other day for 21 days (11 doses) followed by a 7 day drug free period and daily with the established ibrutinib dose for 28 days of a 28-days cycle. Subjects will repeat the 28-day schedule for 2 cycles after a CR or until the cancer progresses or the subject is unable to tolerate the therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Males or non-pregnant, non-breastfeeding females 18 years-of-age or older
- A diagnosis of CLL as defined by IWCLL 2008 criteria and currently on treatment with ibrutinib for at least 18 months with residual disease and without evidence of disease progression.
- No more than 4 prior lines of anti leukemia therapy (not including ibrutinib)
- Life expectancy of at least 9 months
- Karnofsky performance score 70
Key exclusion criteria (16 listed)
- Subjects experiencing toxicity with ibrutinib
- Prior treatment with any Hsp90 inhibitor.
- Major surgery or significant traumatic injury within 4 weeks of starting study treatment.
- Conventional chemotherapy or radiation within 4 weeks.
- The need for treatment with medications with clinically-relevant metabolism by the cytochrome P450 (CYP) 3A4 isoenzyme within 3 hours before or after administration of SNX-5422
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SNX-5422 plus ibrutinibAlso: ImbruvicaSNX-5422 capsule(s) dosed every other day for 21 days out of a 28-day treatment cycle to a total dose of 56 mg/m2 SNX-5422. Subjects will self-administer daily oral ibrutinib in the afternoon at least 8 hours apart from SNX-5422 for 28 days of each cycle. | Drug | SNX-5422 plus ibrutinib |
Primary outcome
Efficacy of the combination of SNX-5422 and ibrutinib
Time frame: 6 months
Proportion of subjects obtaining a complete response at the end of 6 SNX-5422 treatment cycles
4 secondary outcomes
Number of subjects reporting adverse events
Time frame: Day 28 of each 4 week cycle from randomization up to 52 weeks
Complete response at 12 months
Time frame: 12 months
Improved Clinical Status
Time frame: 6 months
Progression free survival of patients receiving ibrutinib plus SNX-5422
Time frame: Up to 52 weeks
Results and safety
The study was stopped early (reason given: Low recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2019.
- Individual participant dataSharing planned: No
Related trials for Cancer
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
Enrolling by invitationPhase 2
A Single-Arm Study of Nimotuzumab Combined With NALIRIFOX as First-Line Treatment for Pancreatic Cancer
Pancreatic Cancer Metastatic
Recruiting
Methylation Profiling in Self-Samples for Identification of (Epi)Genetic Biomarkers for Gynecological Cancers
Gynaecological Cancers, Ovarian Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SNX-5422 plus ibrutinib in people with Cancer, run by Esanex Inc. at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Low recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy of the combination of SNX-5422 and ibrutinib (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2019.