Lymphoma, B CellPhase 1NCT02679196
The Safety, Pharmacokinetic and Pharmacodynamic Effect of KA2237 (PI3 Kinase p110β/δ Inhibitor) In B Cell Lymphoma
A Phase 1 study testing KA2237 in people with Lymphoma, B Cell, run by Karus Therapeutics Limited at 1 site in United States.
Trial summary
Multiple ascending dose study to evaluate safety/tolerability, pharmacokinetic and pharmacodynamics effects of KA2237 (PI3 Kinase p110β/δ Inhibitor) in patients with B Cell Lymphoma and determine the maximum tolerated dose (MTD) in Part I of the study. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma, B Cell
- What is being tested?
- KA2237
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2016to 24 Dec 2018
- 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
- Age ≥18 years at the screening visit.
- Has given written consent to participate in the study.
- Has B-cell lymphoma refractory to or intolerant of established therapy known to provide clinical benefit for their condition and having received rituximab as a single agent or in combination with other therapies.
- Disease status requirement: Measurable disease defined as the presence of ≥ 1 nodal lesion that measures ≥ 1.5 cm in a single dimension as assessed by X-ray Computed Tomography (CT) (Positron Emission Tomography (PET/CT), or magnetic resonance imaging [MRI]
- Eastern Co-operative Oncology Group (ECOG) performance status of ≤ 2.
- For men and women of child-bearing potential, willing to use adequate contraception
Who cannot join
- Subject is a chronic alcoholic (intake > 35 units of alcohol (>5 bottles of wine weekly)) or drug abuser
- Subject has any medical or psychiatric condition that, in the opinion of the Investigator, may compromise the subject's ability to participate in this study
- Female subjects who are breastfeeding, pregnant, or plan to become pregnant during the study or within 3 months following the last dose of investigational product
- Subjects with a current or recent history, as determined by the Investigator, of severe, progressive, and/or uncontrolled renal disease (estimated glomerular filtration rate (eGFR) <30ml/min), hepatic (Alanine transaminase (ALT) 2.5 times upper limit of normal (>2.5xULN), bilirubin > 2x ULN), hematological (absolute neutrophil count (ANC) <1.0 x 109/L, platelet count <75x109/L or requires regular platelet transfusions to maintain a platelet count ≥ 75 x 109/L , hemoglobin <9g/dL), endocrine (glycated Haemoglobin (HbA1c)>7% or random glucose >200mg/dL), pulmonary (Forced Expiratory Volume in 1 second (FEV1) <70% of predicted value), cardiac (New York Heart Association (NYHA)) class III/IV, or neurological disease
- Has had an allogeneic stem cell transplant with current active graft-versus-host-disease.
- Has known active central nervous system involvement of the malignancy.
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- Has active, serious infection requiring systemic therapy. Patients may receive prophylactic antibiotics and antiviral therapy at the discretion of the treating physician.
- Has a positive test for human immunodeficiency virus (HIV) antibodies.
- Has active hepatitis B or C. Patients with serologic evidence of prior exposure are eligible.
- Disease-related exclusions
- Had treatment with a short course of corticosteroids (> 10mg daily prednisone equivalents) for symptom relief within 1-week prior to screening.
- Has poorly controlled diabetes mellitus (HbA1c >7% or random glucose >200mg/dL)
- Known tuberculosis (TB) disease or latent TB infection
- Has chronic, active colitis
- Medication related exclusions
- Had alemtuzumab therapy within 12-weeks prior to screening.
- Has taken a medication that is a potent inhibitor or inducer of cytochrome P450 3A4 (CYP3A4) within 1-week prior to screening.
- The subject has previously participated in this study.
- The subject has participated or is currently participating in another study of an investigational medicine or medical device (radiotherapy, radio-immunotherapy, biological therapy, chemotherapy), within 4-weeks prior to screening.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open Label Ascending Dose Study Evaluating the Safety/Tolerability, Pharmacokinetic and Pharmacodynamic Effects of KA2237 In Patients With B Cell Lymphoma
Multiple ascending dose study to evaluate safety/tolerability, pharmacokinetic and pharmacodynamics effects of KA2237 (PI3 Kinase p110β/δ Inhibitor) in patients with B Cell Lymphoma and determine the maximum tolerated dose (MTD) in Part I of the study. In Part II, patients with B cell lymphoma will be treated with KA2237 at the MTD to evaluate safety and efficacy in the patient population.
- Conditions
- Lymphoma, B Cell
- Being tested
- KA2237
- Medical subject headings
- Lymphoma, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KA2237Drug
Also called PI3 Kinase p110β/δ inhibitor
PI3 Kinase p110β/δ inhibitor
| Study group | Role | What they receive |
|---|---|---|
| KA2237 | Experimental | Open label treatment with KA2237 Receives: Drug: KA2237 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The occurrence of dose limiting toxicity (DLT);
any event with possible or probable relationship to study drug occurring up to day 28 from the start of treatment as assessed using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.03
Measured: Day 28 of treatment
Secondary outcomes (4)
Concentration (mg/ml) of KA2237 in serum/plasma over time (hours)
Measured: 24 weeks
Concentration (mg/ml) of KA2237 in urine over time (hours)
Measured: 24 weeks
Concentration (ng/ml) of key cytokine and intracellular signalling markers in immune cell subsets
Measured: 24 weeks
Frequency of KA2237 related adverse events and laboratory abnormalities
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2016 (estimated)
- Study startJul 2016
- Primary completion24 Dec 2018
- Study completion24 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lymphoma, B CellStudies 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
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karus Therapeutics Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02679196
- Sponsor's protocol ID
- KTP-002
- Status last verified
- Feb 2019
- First submitted
- 29 Jan 2016
- Last updated
- 6 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Nastoupil LJ, Neelapu SS, Davis RE, Samaniego F, Fowler NH, Westin J, Lee HJ, Wang M, Hagemeister F, Cecil ARL, Dow J, Haque K, Silva FA, Whale A, Lensun L, Bone EA, McElwaine-Johnn H, Beer PA. Preclinical and phase I studies of KA2237, a selective and potent inhibitor of PI3K beta/delta in relapsed refractory B cell lymphoma. Leuk Lymphoma. 2021 Dec;62(14):3452-3462. doi: 10.1080/10428194.2021.1957874. Epub 2021 Aug 9.
PubMed 34365878
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Ascending Dose Study Evaluating the Safety/Tolerability, Pharmacokinetic and Pharmacodynamic Effects of KA2237 In Patients With B Cell Lymphoma
- ClinicalTrials.gov ID
- NCT02679196
- Acronym / sponsor ID
- KTP-002
- Conditions
- Lymphoma, B Cell
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Karus Therapeutics LimitedIndustry (pharma, biotech, devices)
- Study start
- Jul 2016
- Primary completion
- 24 Dec 2018 (actual)
- Study completion
- 24 Dec 2018 (actual)
- First posted
- 10 Feb 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.
Multiple ascending dose study to evaluate safety/tolerability, pharmacokinetic and pharmacodynamics effects of KA2237 (PI3 Kinase p110β/δ Inhibitor) in patients with B Cell Lymphoma and determine the maximum tolerated dose (MTD) in Part I of the study. In Part II, patients with B cell lymphoma will be treated with KA2237 at the MTD to evaluate safety and efficacy in the patient population.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| KA2237 | Experimental | Drug: KA2237Open label treatment with KA2237 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age ≥18 years at the screening visit.
- Has given written consent to participate in the study.
- Has B-cell lymphoma refractory to or intolerant of established therapy known to provide clinical benefit for their condition and having received rituximab as a single agent or in combination with other therapies.
- Disease status requirement: Measurable disease defined as the presence of ≥ 1 nodal lesion that measures ≥ 1.5 cm in a single dimension as assessed by X-ray Computed Tomography (CT) (Positron Emission Tomography (PET/CT), or magnetic resonance imaging [MRI]
- Eastern Co-operative Oncology Group (ECOG) performance status of ≤ 2.
Key exclusion criteria (19 listed)
- Subject is a chronic alcoholic (intake > 35 units of alcohol (>5 bottles of wine weekly)) or drug abuser
- Subject has any medical or psychiatric condition that, in the opinion of the Investigator, may compromise the subject's ability to participate in this study
- Female subjects who are breastfeeding, pregnant, or plan to become pregnant during the study or within 3 months following the last dose of investigational product
- Subjects with a current or recent history, as determined by the Investigator, of severe, progressive, and/or uncontrolled renal disease (estimated glomerular filtration rate (eGFR) <30ml/min), hepatic (Alanine transaminase (ALT) 2.5 times upper limit of normal (>2.5xULN), bilirubin > 2x ULN), hematological (absolute neutrophil count (ANC) <1.0 x 109/L, platelet count <75x109/L or requires regular platelet transfusions to maintain a platelet count ≥ 75 x 109/L , hemoglobin <9g/dL), endocrine (glycated Haemoglobin (HbA1c)>7% or random glucose >200mg/dL), pulmonary (Forced Expiratory Volume in 1 second (FEV1) <70% of predicted value), cardiac (New York Heart Association (NYHA)) class III/IV, or neurological disease
- Has had an allogeneic stem cell transplant with current active graft-versus-host-disease.
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 |
|---|---|---|
| KA2237Also: PI3 Kinase p110β/δ inhibitorPI3 Kinase p110β/δ inhibitor | Drug | KA2237 |
Primary outcome
The occurrence of dose limiting toxicity (DLT);
Time frame: Day 28 of treatment
any event with possible or probable relationship to study drug occurring up to day 28 from the start of treatment as assessed using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.03
4 secondary outcomes
Concentration (mg/ml) of KA2237 in serum/plasma over time (hours)
Time frame: 24 weeks
Concentration (mg/ml) of KA2237 in urine over time (hours)
Time frame: 24 weeks
Concentration (ng/ml) of key cytokine and intracellular signalling markers in immune cell subsets
Time frame: 24 weeks
Frequency of KA2237 related adverse events and laboratory abnormalities
Time frame: 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2019.
- Derived from this study: PubMed 34365878Nastoupil LJ, Neelapu SS, Davis RE, Samaniego F, Fowler NH, Westin J, Lee HJ, Wang M, Hagemeister F, Cecil ARL, Dow J, Haque K, Silva FA, Whale A, Lensun L, Bone EA, McElwaine-Johnn H, Beer PA. Preclinical and phase I studies of KA2237, a selective and potent inhibitor of PI3K beta/delta in relapsed refractory B cell lymphoma. Leuk Lymphoma. 2021 Dec;62(14):3452-3462. doi: 10.1080/10428194.2021.1957874. Epub 2021 Aug 9.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing KA2237 in people with Lymphoma, B Cell, run by Karus Therapeutics Limited at 1 site 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 6 inclusion and 19 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: finished, as of the sponsor's last update on 6 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 1 site 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The occurrence of dose limiting toxicity (DLT); (time frame: Day 28 of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02679196, which also lists 1 linked publication.
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 6 Feb 2019.