Alemtuzumab-Ofatumumab in Previously Untreated Symptomatic Chronic Lymphocytic Leukemia

Northwestern University

Status and phase

Active, not recruiting

Phase 2

Conditions

Stage IV Chronic Lymphocytic Leukemia

Stage I Chronic Lymphocytic Leukemia

Stage III Chronic Lymphocytic Leukemia

Stage II Chronic Lymphocytic Leukemia

Treatments

Procedure: biopsy

Biological: alemtuzumab

Biological: ofatumumab

Study type

Interventional

Funder types

Other

NETWORK

Industry

Identifiers

NCT01361711

NCI-2011-00514 (Registry Identifier)

STU00044115 (Other Identifier)

NU 10H06

Details and patient eligibility

About

This phase II trial studies the side effects and how well giving alemtuzumab and ofatumumab together works in treating patients with previously untreated chronic lymphocytic leukemia (CLL). Monoclonal antibodies, such as alemtuzumab and ofatumumab, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer killing substances to them. Giving alemtuzumab together with ofatumumab may kill more cancer cells

Full description

OBJECTIVES:

I. To determine the efficacy and safety of alemtuzumab-ofatumumab combination treatment in previously untreated CLL.

OUTLINE:

Patients receive alemtuzumab subcutaneously (SC) three times a week in weeks 1-18 and ofatumumab intravenously (IV) over 4-6 hours on day 1 of weeks 3, 5, 7, 9, 11, 13, 15, and 17.

After completion of study treatment, patients are followed up for up to 5 years.

Enrollment

53 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients must be Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Patients must have a confirmed diagnosis of CLL as defined by the International Workshop on CLL (iwCLL) 2008 (iwCLL2008) criteria below:
Presence of at least 5x10^9 B lymphocytes/L (5000/uL) in the peripheral blood
Morphologically, the lymphocytes must appear of small to moderate size with < 55% prolymphocytes, atypical lymphocytes or lymphoblasts
The clonality and immunophenotype of the circulating B-lymphocytes must be confirmed by flow cytometry to express CD5, CD23, CD19, CD20, CD52 and either kappa or lambda light chain
Patients must have symptomatic disease requiring therapy; indications for therapy are defined by the iwCLL2008 criteria as follows (one or more are sufficient):
Clinical manifestations (if believed by the investigator to be caused by CLL): a) Unintentional weight loss > 10% within the previous 6 months; b) significant fatigue; c) fevers of greater than 100.5 degrees Fahrenheit (F) (38 degrees Celsius [C]) for 2 weeks without evidence of infection; d) night sweats without evidence of infection
Evidence of progressive marrow failure as manifested by the development or worsening of anemia (< 11 g/dl), thrombocytopenia (< 100,000/mm^3) or neutropenia (< 1,500/mm^3)
Massive (i.e. > 6 cm below left costal margin) or progressive splenomegaly
Massive nodes/clusters (> 5 cm) or progressive symptomatic adenopathy
Progressive lymphocytosis with an increase of > 50% over 2 month period, or an anticipated doubling time of less than 6 months
NOTE: Marked hypogammaglobulinemia or the development of a monoclonal protein in the absence of any of the above criteria for active disease is not sufficient for protocol therapy
Patients must have evidence of adequate bone marrow reserve as shown by absolute neutrophil count (ANC) of at least 1,000/mm^3; however, if the cytopenias are due to extensive bone marrow involvement by CLL, patients may be included in the study
And patients must have evidence of adequate bone marrow reserve as shown by platelet count of at least 50,000/mm^3; however, if the cytopenias are due to extensive bone marrow involvement by CLL, patients may be included in the study
Serum creatinine must be less than 2.0 mg/dl obtained within 2 weeks prior to study enrollment; if serum creatinine is greater than 1.5 mg/dl, the creatinine clearance calculated from a 24 hour urine collection must be greater than 40 ml/min
Total bilirubin must be less than 2 mg/dl (unless due to CLL involvement of liver or a known history of Gilbert's disease)
Aspartate aminotransferase (AST), alanine aminotransferase (ALT) must be no more than 2.5 times upper limit of normal unless due to disease involvement of the liver
Alkaline phosphatase must be no more than 2.5 times upper limit of normal unless due to disease involvement of the liver
All patients must have given a signed, informed consent prior to enrollment on study

Exclusion criteria

Prior cytotoxic therapies are NOT allowed; the only exception is prior corticosteroid therapy (prednisone up to 1 mg/kg for =< 3 months) which must be stopped at least 1 week prior to study enrollment
Patients with active autoimmune anemia or autoimmune thrombocytopenia are NOT eligible
Patients who have current active hepatic or biliary disease (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver involvement by CLL, or stable chronic liver disease per investigator assessment) are NOT eligible
Patients with active chronic or current infections requiring oral or intravenous antibiotics are NOT eligible for enrollment to the study until resolution of the infection and completion of therapeutic antibiotics
Patients with a past or current second malignancy are NOT eligible aside from the following exceptions:
Patients who have been free of malignancy for at least 5 years
Patients who have a history of completely resected basal or squamous cell skin cancer, successfully treated in situ carcinoma of the breast or cervix, or pre-cancerous lesions of the colon
Patients with known human immunodeficiency virus (HIV) are NOT eligible for the study
Patients with history of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae are NOT eligible for the study
Patients with clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to enrollment, congestive heart failure (New York Heart Association [NYHA ] III-IV), and arrhythmia unless controlled by therapy (with the exception of extra systoles or minor conduction abnormalities), are NOT eligible
Patients with significant concurrent, uncontrolled medical condition including, but not limited to, cardiovascular, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the patient, are NOT eligible
Patients with positive serology for Hepatitis B (HB), defined as a positive test for HB surface antigen (HBsAg), are NOT eligible; if negative for HBsAg but HB core antibody (HBcAb) positive a HB deoxyribonucleic acid (DNA) test will be performed; if HB DNA test is positive the patient is NOT eligible; NOTE: patients who are positive for HBcAb but negative for hepatitis B virus (HBV) antigenemia and viremia (HBsAg negative and HB DNA test negative) may be eligible for the study, but must be started on HBV suppression therapy with lamivudine or equivalent anti-HBV agents throughout the treatment and for a year after the completion of the treatments; these patients need to have liver function tests (LFTs) and HBV viral titer monitoring at least monthly during the treatment and for a year after treatment completion
Patients with positive serology for hepatitis C are NOT eligible
Women of childbearing potential and sexually active males must commit to the use of adequate contraception from the study start to one year after the last dose of study treatment
Childbearing potential is defined as any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
Has not undergone a hysterectomy or bilateral oophorectomy; or
Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
Adequate contraception is defined as hormonal birth control, intrauterine device, barrier method or total abstinence; patients who are unable or unwilling to use adequate contraception are NOT eligible
Women who are pregnant or lactating are NOT eligible