The Safety, Pharmacokinetic and Pharmacodynamic Effect of KA2237 (PI3 Kinase p110β/δ Inhibitor) In B Cell Lymphoma

NCT02679196 | Completed Phase 1

• 1 other identifier: KTP-002
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief 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. 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

Outcome Measures

Primary Outcomes (1)

• 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

  Day 28 of treatment

Secondary Outcomes (4)

• Concentration (mg/ml) of KA2237 in serum/plasma over time (hours)

  24 weeks

• Concentration (mg/ml) of KA2237 in urine over time (hours)

  24 weeks

• Concentration (ng/ml) of key cytokine and intracellular signalling markers in immune cell subsets

  24 weeks

• Frequency of KA2237 related adverse events and laboratory abnormalities

  24 weeks

Study Arms (1)

KA2237

EXPERIMENTAL

Open label treatment with KA2237

Drug: KA2237

Interventions

KA2237 DRUG

PI3 Kinase p110β/δ inhibitor

Also known as: PI3 Kinase p110β/δ inhibitor

KA2237

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.
• 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
• 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.

Sponsors & Collaborators

• Karus Therapeutics Limited: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 34365878 DERIVED

MeSH Terms

Conditions

Lymphoma, B-Cell

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2016
• First Posted: February 10, 2016
• Study Start: July 1, 2016
• Primary Completion: December 24, 2018
• Study Completion: December 24, 2018
• Last Updated: February 6, 2019

Record last verified: 2019-02

Locations

US (1)