An Open Label Ascending Dose Study Evaluating the Safety/Tolerability, Pharmacokinetic and Pharmacodynamic Effects of Ka2237 in Patients with B Cell Lymphoma
The goal of this clinical research study is to find the highest tolerable dose of KA2237 that can be given to patients with lymphoma. The safety of this drug will also be studied. This is the first study using KA2237 in humans.
Disease Group: Other diseases of blood and blood-forming organs
Treatment Agent: KA2237
Treatment Location: Both at MDACC & and Other Sites
Sponsor: Karus Therapeutics
Primary Objectives To establish the maximum tolerated dose of KA2237 in patients with B cell lymphoma which has failed to respond to, or relapsed following prior therapy Secondary Objectives Part 1 Escalating MAD: 1. To evaluate the PK profile of KA2237 in patients with B cell lymphoma 2. To evaluate the PD effect of KA2237 treatment on measures of PI3K and â activity in patients with relapsed/refractory B cell lymphoma 3. To evaluate the potential for CYP mediated drug-drug interactions, using midazolam as a probe substrate Part 2 Expansion Cohort: As in Part 1 plus 1. To investigate the effect of the dose of KA2237 selected for further study on overall response rate (ORR) in an extension cohort. 2. To investigate the duration of disease response to KA2237 3. To investigate the time to disease progression Exploratory Objectives: Parts 1 and 2: 1. To evaluate predictive and pharmacodynamic biomarkers after therapy with KA2237 in patients with relapsed/refractory B-cell lymphoma. 2. To evaluate the exposure response relationship of KA2237 3. To evaluate the metabolites of KA2237 in human
IRB Review and Approval Date: 07/15/2016
Recruitment Status: Open
Projected Accrual: 53
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 CT, PET/CT, or magnetic resonance imaging [MRI]
5) ECOG performance status of </= 2.
6) For men and women of child-bearing potential, willing to use adequate contraception (i.e., latex condom, cervical cap, diaphragm, abstinence, etc.) for the entire duration of the study. 1. If female, must be either postmenopausal, sterilised or, if sexually active, effectively practicing an acceptable method of contraception (either oral, parenteral, or implantable hormonal contraceptives, intrauterine device or barrier and spermicide). Subjects must agree to use adequate contraception during the study and for at least 12 weeks (or longer as per local requirement) after the last dose of study treatment. 2. Male subjects agree to ensure that they or their female partner(s) use adequate contraception during the study and for at least 12 weeks (or longer as per local requirement) after the subject receives their last dose of study treatment.
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) Subject has chronic obstructive pulmonary disease with FEV1 (post bronchodilation) <70% predicted at screening.
5) Subject has a past history of pneumonitis on other therapies.
6) Subjects with a current or recent history, as determined by the Investigator, of severe, progressive, and/or uncontrolled renal disease (eGFR </=60ml/min), hepatic (ALT>2.5xULN, bilirubin >/= 1.5 x ULN), hematological (ANC <1.0 x 10^9/L, platelet count <75x10^9/L or requires regular platelet transfusions to maintain a platelet count >/= 75 x 10^9/L , hemoglobin <9g/dL), endocrine (HbA1c>7% or random glucose >200mg/dL), cardiac (NYHA class III/IV), or neurological disease
7) Has had an allogeneic stem cell transplant with current active graft-versus-host-disease.
8) Has known active central nervous system involvement of the malignancy.
9) Has active, serious infection requiring systemic therapy. Patients must receive PJP prophylaxis therapy during receipt of KA2237.
10) Has a positive test for human immunodeficiency virus (HIV) antibodies.
11) Has active hepatitis B or C. Patients with serologic evidence of prior exposure are eligible.
12) Disease-related exclusions: a) Had treatment with a short course of corticosteroids (> 10mg daily prednisone equivalents) for symptom relief within 1-week prior to screening. b) Has poorly controlled diabetes mellitus (HbA1c >7% or random glucose >200mg/dL) c) Known TB disease or latent TB infection d) Has chronic, active colitis
13) Medication related exclusions: a) Had alemtuzumab therapy within 12-weeks prior to screening. b) Requires a concomitant treatment that is either a potent inhibitor or a potent inducer of cytochrome P450 3A4/5. c) The subject has previously participated in this study. d) 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.
Information and next steps
Other diseases of blood and blood-forming organs
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