Aggressive Non-Hodgkin LymphomaPhase 1NCT04372641
Testing the Safety of CB-5339 in Patients With Cancer
A Phase 1 study testing p97 Inhibitor CB-5339 Tosylate in people with Aggressive Non-Hodgkin Lymphoma and Indolent Non-Hodgkin Lymphoma, run by National Cancer Institute (NCI) at 2 sites in United States.
Trial summary
This phase I trial studies the side effects and best dose of CB-5339 in treating patients with solid tumors that has spread to other places in the body (advanced) or lymphomas. CB-5339 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Aggressive Non-Hodgkin Lymphoma, Indolent Non-Hodgkin Lymphoma, Locally Advanced Malignant Solid Neoplasm
- What is being tested?
- p97 Inhibitor CB-5339 Tosylate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- 18 Jun 2020to 12 Jul 2021
- 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
- Patients with histologically documented metastatic or locally advanced (not amenable to surgery) solid tumors whose disease has progressed on standard therapy or for which there is no available standard therapy or therapy known to prolong survival; or aggressive lymphoma who have refused or have no remaining curative options (e.g., stem cell transplant). Patients with indolent lymphomas must have undergone 3 or more prior regimens of therapy
- Any prior therapy must have been completed >= 4 weeks (6 weeks for nitrosoureas and mitomycin C) or, if known, >= 5 half-lives of the prior agent (whichever is shorter) prior to enrollment on protocol (minimum of 1 week between prior therapy and study enrollment), and the participant must have recovered to eligibility levels from prior toxicity. Prior definitive radiation should have been completed >= 4 weeks or palliative radiation should have been completed >= 2 weeks prior to study enrollment and all associated toxicities resolved to eligibility levels (patients on study may be eligible for palliative radiotherapy to non-targeted lesions after 2 cycles of therapy at the principal investigator [PI]'s discretion). Patients must be >= 2 weeks since any investigational agent administered as part of a phase 0 study (where a sub-therapeutic dose of drug is administered) at the PI's discretion and should have recovered to grade 1 or baseline from any toxicities
- Patients who have had prior monoclonal antibody therapy must have completed that therapy >= 6 weeks (or 3 half-lives of the antibody, whichever is shorter) prior to enrollment on protocol (minimum of 1 week between prior therapy and study enrollment)
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) and life expectancy > 3 months
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 100,000/mcL (solid tumor patients)
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- Platelets >= 75,000/mcL (lymphoma patients)
- Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN
- Creatinine =< 1.5 x institutional ULN OR 60 mL/min/1.73 m^2 for patients with creatinine levels above 1.5 x institutional normal
- The effects of CB-5339 on the developing human fetus are unknown. For this reason and because p97 inhibitors agents may be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for 4 months afterwards. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of CB-5339 administration
- Ability to understand and the willingness to sign a written informed consent document
- Subjects on the expansion cohort must also be willing to undergo two core biopsy procedures if there is a lesion amenable to biopsy
- Left ventricular ejection fraction >= the lower limit of normal by echocardiogram (ECHO) at entry
- Mean QT interval corrected for heart rate (QTc) < 470 ms using Fridericia's correction
Who cannot join
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia
- Patients who are receiving any other investigational agents
- Patients with clinically significant illnesses which would compromise participation in the study, including but not limited to active or uncontrolled infection, immune deficiencies, hepatitis B, hepatitis C, active tuberculosis, uncontrolled asthma, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, myocardial infarction within the past 6 months, cerebral vascular accident/stroke within the past 6 months, or psychiatric illness/social situations that would limit compliance with study requirements.
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
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- Patients with known brain metastases or carcinomatous meningitis are excluded from this clinical trial, with the exception of patients whose brain metastatic disease status has remained stable for >= 4 weeks after treatment of the brain metastases. Patients on anti-seizure medications may be enrolled at the discretion of the principal investigator providing that these patients are taking non-enzyme- inducing anti-seizure medications or can be converted to these
- Pregnant women are excluded from this study because CB-5339 may have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with this agent, breastfeeding should be discontinued if the mother is treated with CB-5339
- Current or previous history of sight-threatening retinal disease, including (but not limited to) proliferative diabetic retinopathy, severe retinal vascular disease, and advanced age-related macular degeneration
- Patients with a history of QT-prolongation or of Torsades de pointes (TdP), or of taking QT-prolonging drugs, are not eligible
Trial locations and contacts
2 sites in 1 country.
United States2 sites
National Cancer Institute Developmental Therapeutics Clinic
Bethesda, Maryland, 20892
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: A Phase I Trial of the P97 Inhibitor CB-5339 in Patients With Advanced Solid Tumors and Lymphomas
This phase I trial studies the side effects and best dose of CB-5339 in treating patients with solid tumors that has spread to other places in the body (advanced) or lymphomas. CB-5339 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
PRIMARY OBJECTIVE:
- To establish the safety, tolerability, and recommended phase 2 dose (RP2D) of p97 inhibitor CB-5339 tosylate (CB-5339) administered orally on a schedule of once daily, 4 days on and 3 days off, in patients with advanced solid tumors and lymphomas.
SECONDARY OBJECTIVES:
- To evaluate the pharmacokinetic profiles of CB-5339. II. To assess the preliminary antitumor activity of CB-5339 in patients with advanced solid tumors and lymphomas.
III. To determine the effects of CB-5339 on the ubiquitin proteasome system and on markers of cell death in pre- and post-treatment tumor biopsies and peripheral blood mononuclear cell (PBMC)s.
EXPLORATORY OBJECTIVE:
- To evaluate potential associations between CB-5339 activity and genomic alterations assessed in circulating tumor deoxyribonucleic acid (DNA) (ctDNA).
OUTLINE: This is a dose-escalation study.
Patients receive p97 inhibitor CB-5339 tosylate orally (PO) once daily (QD) 4 days on and 3 days off. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
- Conditions
- Aggressive Non-Hodgkin Lymphoma, Indolent Non-Hodgkin Lymphoma, Locally Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm
- Being tested
- p97 Inhibitor CB-5339 Tosylate
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
p97 Inhibitor CB-5339 TosylateDrug
Also called CB 5339 Tosylate, CB-5339 Tosylate, CB5339 Tosylate
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (p97 inhibitor CB-5339 tosylate) | Experimental | Patients receive p97 inhibitor CB-5339 tosylate PO QD 4 days on and 3 days off. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: p97 Inhibitor CB-5339 Tosylate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events (Phase I)
Measured: 30 days
Recommended phase II dose (Phase I)
Measured: 30 days
Secondary outcomes (2)
Pharmacodynamic analysis (expansion phase)
Measured: Up to 2 years
Response assessment
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2020
- Study start18 Jun 2020 (estimated)
- Primary completion12 Jul 2021 (estimated)
- Study completion12 Jul 2021 (estimated)
Why it stopped: Other - Clinical development of the agent has been discontinued
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Aggressive Non-Hodgkin LymphomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Naoko Takebe, Principal investigator, National Cancer Institute LAO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04372641
- Sponsor's protocol ID
- NCI-2019-08664
- Other IDs
- NCI-2019-08664, 10349, 10349
- Status last verified
- Sep 2025
- First submitted
- 1 May 2020
- Last updated
- 17 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of the P97 Inhibitor CB-5339 in Patients With Advanced Solid Tumors and Lymphomas
- ClinicalTrials.gov ID
- NCT04372641
- Acronym / sponsor ID
- NCI-2019-08664
- Conditions
- Aggressive Non-Hodgkin Lymphoma, Indolent Non-Hodgkin Lymphoma, Locally Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Other - Clinical development of the agent has been discontinued
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 18 Jun 2020 (estimated)
- Primary completion
- 12 Jul 2021 (estimated)
- Study completion
- 12 Jul 2021 (estimated)
- First posted
- 4 May 2020 (actual)
- 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.
This phase I trial studies the side effects and best dose of CB-5339 in treating patients with solid tumors that has spread to other places in the body (advanced) or lymphomas. CB-5339 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVE:
- To establish the safety, tolerability, and recommended phase 2 dose (RP2D) of p97 inhibitor CB-5339 tosylate (CB-5339) administered orally on a schedule of once daily, 4 days on and 3 days off, in patients with advanced solid tumors and lymphomas.
SECONDARY OBJECTIVES:
- To evaluate the pharmacokinetic profiles of CB-5339. II. To assess the preliminary antitumor activity of CB-5339 in patients with advanced solid tumors and lymphomas.
III. To determine the effects of CB-5339 on the ubiquitin proteasome system and on markers of cell death in pre- and post-treatment tumor biopsies and peripheral blood mononuclear cell (PBMC)s.
EXPLORATORY OBJECTIVE:
- To evaluate potential associations between CB-5339 activity and genomic alterations assessed in circulating tumor deoxyribonucleic acid (DNA) (ctDNA).
OUTLINE: This is a dose-escalation study.
Patients receive p97 inhibitor CB-5339 tosylate orally (PO) once daily (QD) 4 days on and 3 days off. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (p97 inhibitor CB-5339 tosylate) | Experimental | Drug: p97 Inhibitor CB-5339 TosylatePatients receive p97 inhibitor CB-5339 tosylate PO QD 4 days on and 3 days off. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patients with histologically documented metastatic or locally advanced (not amenable to surgery) solid tumors whose disease has progressed on standard therapy or for which there is no available standard therapy or therapy known to prolong survival; or aggressive lymphoma who have refused or have no remaining curative options (e.g., stem cell transplant). Patients with indolent lymphomas must have undergone 3 or more prior regimens of therapy
- Any prior therapy must have been completed >= 4 weeks (6 weeks for nitrosoureas and mitomycin C) or, if known, >= 5 half-lives of the prior agent (whichever is shorter) prior to enrollment on protocol (minimum of 1 week between prior therapy and study enrollment), and the participant must have recovered to eligibility levels from prior toxicity. Prior definitive radiation should have been completed >= 4 weeks or palliative radiation should have been completed >= 2 weeks prior to study enrollment and all associated toxicities resolved to eligibility levels (patients on study may be eligible for palliative radiotherapy to non-targeted lesions after 2 cycles of therapy at the principal investigator [PI]'s discretion). Patients must be >= 2 weeks since any investigational agent administered as part of a phase 0 study (where a sub-therapeutic dose of drug is administered) at the PI's discretion and should have recovered to grade 1 or baseline from any toxicities
- Patients who have had prior monoclonal antibody therapy must have completed that therapy >= 6 weeks (or 3 half-lives of the antibody, whichever is shorter) prior to enrollment on protocol (minimum of 1 week between prior therapy and study enrollment)
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) and life expectancy > 3 months
- Absolute neutrophil count >= 1,500/mcL
Key exclusion criteria (10 listed)
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia
- Patients who are receiving any other investigational agents
- Patients with clinically significant illnesses which would compromise participation in the study, including but not limited to active or uncontrolled infection, immune deficiencies, hepatitis B, hepatitis C, active tuberculosis, uncontrolled asthma, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, myocardial infarction within the past 6 months, cerebral vascular accident/stroke within the past 6 months, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients with known brain metastases or carcinomatous meningitis are excluded from this clinical trial, with the exception of patients whose brain metastatic disease status has remained stable for >= 4 weeks after treatment of the brain metastases. Patients on anti-seizure medications may be enrolled at the discretion of the principal investigator providing that these patients are taking non-enzyme- inducing anti-seizure medications or can be converted to these
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 |
|---|---|---|
| p97 Inhibitor CB-5339 TosylateAlso: CB 5339 Tosylate, CB-5339 Tosylate, CB5339 TosylateGiven PO | Drug | Treatment (p97 inhibitor CB-5339 tosylate) |
Primary outcome
Incidence of adverse events (Phase I)
Time frame: 30 days
Recommended phase II dose (Phase I)
Time frame: 30 days
2 secondary outcomes
Pharmacodynamic analysis (expansion phase)
Time frame: Up to 2 years
Response assessment
Time frame: Up to 2 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2025.
- Individual participant dataSharing planned: Yes. NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
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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.
Naoko Takebe principal investigator
National Cancer Institute LAO
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 p97 Inhibitor CB-5339 Tosylate in people with Aggressive Non-Hodgkin Lymphoma and Indolent Non-Hodgkin Lymphoma, run by National Cancer Institute (NCI) 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 15 inclusion and 10 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: withdrawn, as of the sponsor's last update on 17 Sep 2025. 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 withdrawn before enrolling participants, so there are no results.
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?
Incidence of adverse events (Phase I) (time frame: 30 days). The study lists 2 primary outcomes in all. 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 17 Sep 2025.