Akt Inhibitor MK2206, Bendamustine Hydrochloride, and Rituximab in Treating Patients With Relapsed Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Completed · Phase 1/Phase 2

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

In brief

This phase I/II trial studies the side effects and best dose of v-akt murine thymoma viral oncogene homolog 1 (Akt) inhibitor MK2206 when given together with bendamustine hydrochloride and rituximab and to see how well they work in treating patients with refractory chronic lymphocytic leukemia or small lymphocytic lymphoma. Akt inhibitor MK2206 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as bendamustine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving Akt inhibitor MK2206 with bendamustine hydrochloride and rituximab may be an effective treatment for relapsed chronic lymphocytic leukemia or small lymphocytic lymphoma.

Key facts

Study ID

NCT01369849

Run by

National Cancer Institute (NCI)

People needed

15

Starts

2011-09-01

Expected to finish

2014-02-01

Last updated by the study team

2017-09-15

Who can join

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

You may qualify if…

• Diagnosis of chronic lymphocytic leukemia (CLL) according to the National Cancer Institute (NCI) criteria or small lymphocytic lymphoma (SLL) according to the World Health Organization (WHO) criteria; this includes previous documentation of:
• Biopsy-proven SLL or
• Diagnosis of CLL according to NCI working group criteria as evidenced by all of the following:
• Peripheral blood B-cell count of > 5 x 10\^9/L consisting of small to moderate size lymphocytes
• Immunophenotyping consistent with CLL defined as:
• The predominant population of lymphocytes share both B-cell antigens (CD19, CD20 [typically dim expression], or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3,CD2, etc.)
• Clonality as evidenced by kappa (Κ) or lambda (λ) light chain expression (typically dim immunoglobulin expression) or other genetic method (e.g., immunoglobulin heavy chain variable [IGHV] analysis)
• NOTE: splenomegaly, hepatomegaly, or lymphadenopathy are not required for the diagnosis of CLL
• Before diagnosing CLL or SLL, mantle cell lymphoma must be excluded by demonstrating a negative fluorescence in situ hybridization (FISH) analysis for t (11;14) (IgH/CCND1) on peripheral blood or tissue biopsy, or negative immunohistochemical stains for cyclin D1 on involved tissue biopsy
• Demonstrated progression after one or two prior lines of CLL therapy; note: rituximab monotherapy does not count as a prior line of therapy
• Progressive disease with any one of the following characteristics based on standard criteria for treatment as defined by the NCI-Working Group (WG) 1996
• Symptomatic CLL characterized by any one of the following:
• Weight loss >= 10% within the previous 6 months
• Extreme fatigue attributed to CLL
• Fevers > 100.5° Fahrenheit (F) for 2 weeks without evidence of infection
• Drenching night sweats without evidence of infection
• Evidence of progressive bone marrow failure with hemoglobin < 11 g/dL or platelet count < 100 x 10\^9/L
• Massive or rapidly progressive splenomegaly (> 6 cm below left costal margin)
• Massive (> 10 cm) or rapidly progressive lymphadenopathy
• Life expectancy >= 12 months
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) unless due to Gilbert's disease; if total bilirubin is > 1.5 x ULN, a direct bilirubin should be performed and must be < 1.5 mg/dL for Gilbert's to be diagnosed
• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2.5 ULN
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 times ULN
• Creatinine =< 1.5 times ULN OR creatinine clearance >= 60 mL/min/1.73 m\^2 for patients with creatinine levels > 1.5 x ULN

You may not qualify if…

• Prior treatment with bendamustine
• Prior treatment with any experimental Akt inhibitors
• More than 2 previous purine nucleoside based-therapy (i.e. fludarabine, pentostatin, or cladribine)
• More than 2 previous alkylating agent based-therapy (i.e. cyclophosphamide, chlorambucil)
• More than 3 total prior lines of therapy for CLL
• Primary refractory disease as defined by progression while receiving or within 6 months of completion of a chemoimmunotherapy regimen such as fludarabine, cyclophosphamide and rituximab (FCR) or pentostatin, cyclophosphamide and rituximab (PCR)
• PHASE II ONLY: FISH abnormality of 17P deletions; (note: patients with 17P deletions will be included in Phase I but will be excluded in Phase II unless enough activity is found in the Phase I)
• Pregnant women
• Nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens; including but not limited to the following:
• New York Heart Association class III or IV heart disease
• Recent myocardial infarction (< 1 month)
• Uncontrolled infection
• Known infection with the human immunodeficiency virus (HIV/acquired immune deficiency syndrome [AIDS]) and/or patients taking highly active antiretroviral therapy (HAART) as further severe immunosuppression with this regimen may occur
• Infection with known chronic, active hepatitis C
• Positive serology for hepatitis B (HB) defined as a positive test for hepatitis B surface antigen (HBsAg); in addition, if negative for HBsAg but hepatitis B core antibody (HBcAb) positive (regardless of hepatitis B surface antibody [HBsAb] status), a HB deoxyribonucleic acid (DNA) test will be performed and if positive the subject will be excluded
• Uncontrolled diabetes defined as hemoglobin A1c (HbA1c) >= 8 or fasting blood glucose >= 140 mg/dL
• Any of the following:
• History of significant ventricular arrhythmia in the last 5 years including: ventricular tachycardia or ventricular fibrillation
• Corrected QT (QTc) prolongation on baseline electrocardiogram (ECG) (defined as a QTc interval > 450 msec for males and QTc interval > 470 msec for females)
• Currently using a medication known to cause prolonged QTc which cannot be discontinued; note: other medications with possible risk of prolonged QTc are allowed but should be used with caution; patients using these medications should be monitored accordingly
• Ventricular arrhythmia on baseline ECG (ventricular tachycardia or ventricular fibrillation >= 3 beats in a row)
• Second or third degree heart block
• Receiving any other investigational agent concurrently which would be considered as a treatment for the primary neoplasm

Where it is running

• Mayo Clinic in Arizona — Scottsdale, Arizona, United States
• Siouxland Regional Cancer Center — Sioux City, Iowa, United States
• Mercy Medical Center-Sioux City — Sioux City, Iowa, United States
• Saint Luke's Regional Medical Center — Sioux City, Iowa, United States
• Essentia Health Saint Joseph's Medical Center — Brainerd, Minnesota, United States
• Fairview Ridges Hospital — Burnsville, Minnesota, United States
• Mercy Hospital — Coon Rapids, Minnesota, United States
• Essentia Health Cancer Center — Duluth, Minnesota, United States
• Essentia Health Saint Mary's Medical Center — Duluth, Minnesota, United States
• Miller-Dwan Hospital — Duluth, Minnesota, United States
• Fairview-Southdale Hospital — Edina, Minnesota, United States
• Unity Hospital — Fridley, Minnesota, United States
• Hutchinson Area Health Care — Hutchinson, Minnesota, United States
• Minnesota Oncology Hematology PA-Maplewood — Maplewood, Minnesota, United States
• Saint John's Hospital - Healtheast — Maplewood, Minnesota, United States
• Abbott-Northwestern Hospital — Minneapolis, Minnesota, United States
• Hennepin County Medical Center — Minneapolis, Minnesota, United States
• North Memorial Medical Health Center — Robbinsdale, Minnesota, United States
• Mayo Clinic — Rochester, Minnesota, United States
• Metro-Minnesota NCI Community Oncology Research Program — Saint Louis Park, Minnesota, United States
• Park Nicollet Clinic - Saint Louis Park — Saint Louis Park, Minnesota, United States
• Regions Hospital — Saint Paul, Minnesota, United States
• United Hospital — Saint Paul, Minnesota, United States
• Saint Francis Regional Medical Center — Shakopee, Minnesota, United States
• Lakeview Hospital — Stillwater, Minnesota, United States

Full record on ClinicalTrials.gov

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