Akt Inhibitor MK2206, Bendamustine Hydrochloride, and Rituximab in Treating Patients With Relapsed Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Phase I/II Study of the Combination of Bendamustine, Rituximab and MK-2206 in the Treatment of Relapsed Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma
6 other identifiers
interventional
15
1 country
44
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Sep 2011
Typical duration for phase_1
44 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 8, 2011
CompletedFirst Posted
Study publicly available on registry
June 9, 2011
CompletedStudy Start
First participant enrolled
September 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
February 1, 2014
CompletedResults Posted
Study results publicly available
June 28, 2016
CompletedSeptember 15, 2017
August 1, 2017
2.4 years
June 8, 2011
May 20, 2016
August 17, 2017
Conditions
Outcome Measures
Primary Outcomes (2)
Number of Phase I Participants With Dose-Limiting Toxicity Events (Phase I)
The Maximum Tolerated Dose (MTD) is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients graded according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Dose-limiting toxicities include non-hematologic events graded 3 or higher and deemed at least possibly related to treatment. A total of 6 patients treated at the MTD will be sufficient to identify common toxicities at the MTD.The number of patients reporting a dose-limiting event are reported.
Up to 35 days
Proportion of Complete Response Defined to be a CR or CRi Noted as the Objective Status (Phase II)
A Complete Response (CR) is defined by the NCI Working Group criteria and requires all of the following for a period of at least 2 months: * Absence of lymphadenopathy (e.g. lymph nodes \>1.5 cm) by physical examination. * No hepatomegaly or splenomegaly by physical examination. * Absence of constitutional symptoms. * Neutrophils ≥1500/ul. * Platelets \>100,000/ul (untransfused). * Hemoglobin \>11.0 gm/dl (untransfused) * Peripheral blood lymphocytes \<4000/uL Patients who fulfill all criteria for a CR but who have a persistent anemia, thrombocytopenia, or neutropenia related to drug toxicity rather than residual CLL will be classified as CR with incomplete marrow recovery (CRi). The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.
From registration to response, up to 84 days
Secondary Outcomes (7)
Biomarker Analysis (IgVH Gene Mutation)
Baseline
Biomarker Analysis (CD38, CD49d, and ZAP-70)
Baseline
Fluorescent in Situ Hybridization (FISH) Biomarker Analysis
Baseline
Duration of Response
Median follow-up of 39 months and maximum follow-up of 54 months
Minimal-residual Disease
Cycle 6 assessment (maximum of 231 days post-registration)
- +2 more secondary outcomes
Study Arms (1)
Treatment (Akt inhibitor MK2206, bendamustine, rituximab)
EXPERIMENTALPatients receive Akt inhibitor MK2206 PO on days 1, 8, 15, and 22 (days 1, 8, 15, 22, and 29 of course 1); rituximab IV on day 1 (day 8 of course 1); and bendamustine hydrochloride IV over 30-60 minutes on days 1-2 (days 8-9 of course 1). Treatment repeats every 28 days (35 days for course 1 and 84 days for course 6) for 6 courses in the absence of disease progression or unacceptable toxicity.
Interventions
Given PO
Given IV
Correlative studies
Given IV
Eligibility Criteria
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
- +23 more criteria
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
- +45 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (44)
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259, United States
Siouxland Regional Cancer Center
Sioux City, Iowa, 51101, United States
Mercy Medical Center-Sioux City
Sioux City, Iowa, 51104, United States
Saint Luke's Regional Medical Center
Sioux City, Iowa, 51104, United States
Essentia Health Saint Joseph's Medical Center
Brainerd, Minnesota, 56401, United States
Fairview Ridges Hospital
Burnsville, Minnesota, 55337, United States
Mercy Hospital
Coon Rapids, Minnesota, 55433, United States
Essentia Health Cancer Center
Duluth, Minnesota, 55805, United States
Essentia Health Saint Mary's Medical Center
Duluth, Minnesota, 55805, United States
Miller-Dwan Hospital
Duluth, Minnesota, 55805, United States
Fairview-Southdale Hospital
Edina, Minnesota, 55435, United States
Unity Hospital
Fridley, Minnesota, 55432, United States
Hutchinson Area Health Care
Hutchinson, Minnesota, 55350, United States
Minnesota Oncology Hematology PA-Maplewood
Maplewood, Minnesota, 55109, United States
Saint John's Hospital - Healtheast
Maplewood, Minnesota, 55109, United States
Abbott-Northwestern Hospital
Minneapolis, Minnesota, 55407, United States
Hennepin County Medical Center
Minneapolis, Minnesota, 55415, United States
North Memorial Medical Health Center
Robbinsdale, Minnesota, 55422, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Metro-Minnesota NCI Community Oncology Research Program
Saint Louis Park, Minnesota, 55416, United States
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, 55416, United States
Regions Hospital
Saint Paul, Minnesota, 55101, United States
United Hospital
Saint Paul, Minnesota, 55102, United States
Saint Francis Regional Medical Center
Shakopee, Minnesota, 55379, United States
Lakeview Hospital
Stillwater, Minnesota, 55082, United States
Ridgeview Medical Center
Waconia, Minnesota, 55387, United States
Rice Memorial Hospital
Willmar, Minnesota, 56201, United States
Minnesota Oncology and Hematology PA-Woodbury
Woodbury, Minnesota, 55125, United States
Adena Regional Medical Center
Chillicothe, Ohio, 45601, United States
Riverside Methodist Hospital
Columbus, Ohio, 43214, United States
Columbus CCOP
Columbus, Ohio, 43215, United States
Grant Medical Center
Columbus, Ohio, 43215, United States
Mount Carmel Health Center West
Columbus, Ohio, 43222, United States
Doctors Hospital
Columbus, Ohio, 43228, United States
Grady Memorial Hospital
Delaware, Ohio, 43015, United States
Fairfield Medical Center
Lancaster, Ohio, 43130, United States
Marietta Memorial Hospital
Marietta, Ohio, 45750, United States
Knox Community Hospital
Mount Vernon, Ohio, 43050, United States
Licking Memorial Hospital
Newark, Ohio, 43055, United States
Southern Ohio Medical Center
Portsmouth, Ohio, 45662, United States
Springfield Regional Medical Center
Springfield, Ohio, 45505, United States
Saint Ann's Hospital
Westerville, Ohio, 43081, United States
Genesis HealthCare System
Zanesville, Ohio, 43701, United States
Rapid City Regional Hospital
Rapid City, South Dakota, 57701, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Wei Ding, MBBS, PhD
- Organization
- Mayo Clinic
Study Officials
- PRINCIPAL INVESTIGATOR
Wei Ding
Alliance for Clinical Trials in Oncology
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 8, 2011
First Posted
June 9, 2011
Study Start
September 1, 2011
Primary Completion
February 1, 2014
Study Completion
February 1, 2014
Last Updated
September 15, 2017
Results First Posted
June 28, 2016
Record last verified: 2017-08