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

• ClinicalTrials.gov Identifier: NCT02679196
• Recruitment Status: Completed
• First Posted: February 10, 2016
• Last Update Posted: February 6, 2019
• Sponsor: Karus Therapeutics Limited
• Information provided by (Responsible Party): Karus Therapeutics Limited

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Lymphoma, B Cell	Drug: KA2237	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 23 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label Ascending Dose Study Evaluating the Safety/Tolerability, Pharmacokinetic and Pharmacodynamic Effects of KA2237 In Patients With B Cell Lymphoma
• Study Start Date: July 2016
• Actual Primary Completion Date: December 24, 2018
• Actual Study Completion Date: December 24, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: KA2237; Open label treatment with KA2237	Drug: KA2237; PI3 Kinase p110β/δ inhibitor; Other Name: PI3 Kinase p110β/δ inhibitor

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. Concentration (mg/ml) of KA2237 in serum/plasma over time (hours) [ Time Frame: 24 weeks ]
2. Concentration (mg/ml) of KA2237 in urine over time (hours) [ Time Frame: 24 weeks ]
3. Concentration (ng/ml) of key cytokine and intracellular signalling markers in immune cell subsets [ Time Frame: 24 weeks ]
4. Frequency of KA2237 related adverse events and laboratory abnormalities [ Time Frame: 24 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Age ≥18 years at the screening visit.
2. Has given written consent to participate in the study.
3. 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.
4. 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]
5. Eastern Co-operative Oncology Group (ECOG) performance status of ≤ 2.
6. For men and women of child-bearing potential, willing to use adequate contraception

Exclusion Criteria:

1. Subject is a chronic alcoholic (intake > 35 units of alcohol (>5 bottles of wine weekly)) or drug abuser
2. 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
3. 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
4. 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
5. Has had an allogeneic stem cell transplant with current active graft-versus-host-disease.
6. Has known active central nervous system involvement of the malignancy.
7. Has active, serious infection requiring systemic therapy. Patients may receive prophylactic antibiotics and antiviral therapy at the discretion of the treating physician.
8. Has a positive test for human immunodeficiency virus (HIV) antibodies.
9. Has active hepatitis B or C. Patients with serologic evidence of prior exposure are eligible.

10. 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

11. 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.

Contacts and Locations

Locations

United States, Texas

MD Anderson Cancer Center

Houston, Texas, United States, 77030

Sponsors and Collaborators

Karus Therapeutics Limited

More Information

• Responsible Party: Karus Therapeutics Limited
• ClinicalTrials.gov Identifier: NCT02679196
• Other Study ID Numbers: KTP-002
• First Posted: February 10, 2016
• Last Update Posted: February 6, 2019
• Last Verified: February 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Additional relevant MeSH terms:

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