Buparlisib and Ofatumumab or Ibrutinib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

Stopped early · Phase 1

Conditions studied: Recurrent Chronic Lymphocytic Leukemia, Recurrent Small Lymphocytic Lymphoma, Refractory Chronic Lymphocytic Leukemia, Refractory Small Lymphocytic Lymphoma

In brief

This phase I trial studies the side effects and best dose of buparlisib when given together with ofatumumab or ibrutinib in treating patients with chronic lymphocytic leukemia that has returned after a period of improvement or does not respond to treatment. Buparlisib and ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as ofatumumab, may block cancer growth in different ways by targeting certain cells. Giving buparlisib or ibrutinib and ofatumumab together may work better in treating patients with chronic lymphocytic leukemia.

Key facts

Study ID

NCT02614508

Run by

Emory University

People needed

1

Starts

2016-01-01

Expected to finish

2019-08-01

Last updated by the study team

2019-09-03

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients must have histologically confirmed B-cell chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) according to World Health Organization (WHO) criteria with at least one of the following indications for treatment:
• Progressive disease or marked splenomegaly or hepatomegaly
• Anemia (hemoglobin [Hgb] < 11 mg/dL) or thrombocytopenia (platelets < 100,000 /mm³)
• Unexplained weight loss exceeding 10% of body weight over the preceding 6 months
• Fevers > 100.5° F or night sweats for greater than 2 weeks without evidence of infection
• Progressive lymphocytosis, with an increase exceeding 50% over a 2 month period or a doubling time of less than 6 months
• Significant fatigue (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v] 4.03 grade 2 or higher)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• At least one prior therapy for CLL/SLL; prior autologous or allogeneic stem cell transplant is allowed; patients may not be on chronic immunosuppressive therapy for graft-versus-host disease (GVHD); patients who are on only oral steroids must be on an oral dose of 10mg or less of prednisone (or equivalent) daily
• Prior therapy with a selective phosphoinositide 3-kinase (PI3K) inhibitor or other B-cell receptor targeting agents is allowed
• Patients who have been previously treated with ibrutinib (or any Bruton's tyrosine kinase [BTK] inhibitor) are eligible for the ibrutinib pre-treated cohort as long as prior ibrutinib or BTK inhibitor therapy was not discontinued due to toxicity/adverse event; there is no minimum dose of ibrutinib; any prior administration will disqualify patients for the ibrutinib-naïve cohort and will require enrollment on the ibrutinib pre-treated cohort
• Serum creatinine ≤ 1.5 x upper limit of normal (ULN) and/or creatinine clearance > 50% lower limit of normal
• Total bilirubin ≤ upper limit of normal (or ≤ 1.5 x upper limit of normal if live metastases are present; or total bilirubin ≤ 3.0 x upper limit of normal with direct bilirubin within normal range in patients with well documented Gilbert's syndrome, which is defined as presence of several episodes of unconjugated hyperbilirubinemia with normal results from complete blood count [CBC] count [including normal reticulocyte count and blood smear], normal liver function test results, and absence of other contributing disease processes at the time of diagnosis)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ upper limit of normal (or < 3.0 x ULN if liver metastases are present)
• Serum lipase ≤ upper limit of normal
• Serum amylase ≤ upper limit of normal
• International normalized ratio (INR) ≤ 1.5
• Fasting glucose ≤ 120 mg/dL
• Absolute neutrophil count ≥ 1000/mm³
• Platelets ≥ 50,000/mm³
• Potassium within normal limits (oral supplementation is allowed)
• Calcium (corrected for albumin) within normal limits (oral supplementation is allowed)
• Hemoglobin A1c (HbA1c) ≤ 8%
• Recovery to ≤ grade 1 toxicities associated with prior therapy
• Negative serum pregnancy test within 72 hours before starting study treatment in women with childbearing potential

You may not qualify if…

• Patient has a known hypersensitivity to any of the excipients of buparlisib
• Patient who has received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered to grade 1 or better from related side effects of such therapy (except alopecia)
• Patient has not recovered to grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy
• Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects
• Patient is currently receiving increasing or chronic treatment (> 5 days) with corticosteroids or another immunosuppressive agent, as chronic administration of corticosteroids (> 5 days) can induce cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4); see also section "concomitant medication"; the following uses of corticosteroids are permitted: single doses; e.g. with standard premedication for infusions; topical applications (e.g., rash), inhaled sprays (e.g., obstructive airways diseases), eye drops or local injections (e.g., intra-articular); patients may take 10mg or less (or equivalent) of oral prednisone daily
• Patient is being treated at start of study treatment with any of the following drugs:
• Drugs known to be strong inhibitors or inducers of isoenzyme CYP3A4 including herbal medications
• Drugs with a known risk to induce Torsades de Pointes
• Note: the patient must have discontinued strong inducers for at least one week and must have discontinued strong inhibitors before the treatment is initiated; switching to a different medication prior to starting study treatment is allowed
• Patient is currently receiving warfarin or other coumarin derived anti-coagulant, for treatment, prophylaxis or otherwise; therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed
• Patients who have other concurrent severe and/or uncontrolled medical conditions that would, in the investigator's judgment, contraindicate patient participation in the clinical study (eg. active or uncontrolled severe infection, chronic active hepatitis, immuno-compromised, acute or chronic pancreatitis, uncontrolled high blood pressure, interstitial lung disease, etc.)
• Patient has a known history of human immunodeficiency virus (HIV) infection (testing not mandatory)
• Patients has any of the following cardiac abnormalities:
• Symptomatic congestive heart failure
• History of documented congestive heart failure (New York Heart Association functional classification III-IV), documented cardiomyopathy
• Left ventricular ejection fraction < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)
• Myocardial infarction ≤ 6 months prior to enrollment
• Unstable angina pectoris
• Serious uncontrolled cardiac arrhythmia
• Symptomatic pericarditis
• Corrected QT interval using Fridericia's formula (QTcF) > 480 msec on the screening electrocardiogram (ECG) (using the QTcF formula)
• Currently receiving treatment with medication that has a known risk to prolong the QT interval or inducing Torsades de Pointes, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug
• Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
• Patient has a score ≥ 12 on the Patient Health Questionnaire (PHQ)-9 questionnaire
• Patient selects a response of "1, 2 or 3" to question number 9 on the PHQ-9 questionnaire regarding potential for suicidal thoughts or ideation (independent of the total score of the PHQ-9)

Where it is running

• Emory University/Winship Cancer Institute — Atlanta, Georgia, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.