Alemtuzumab-Ofatumumab in Previously Untreated Symptomatic Chronic Lymphocytic Leukemia

NCT01361711 | Active Not Recruiting Phase 2 Results DMC

• 3 other identifiers: NU 10H06NCI-2011-00514STU00044115
• Study Type: interventional
• Target: 53
• Locations: 2 countries
• Sites: 2

Brief Summary

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

Conditions

Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Best Response as Defined by the iwCLL2008 (International Workshop on Chronic Lymphocytic Leukemia 2008)

  CR= Absence of clonal lymphocytes in the peripheral blood, significant lymphadenopathy, hepatomegaly or splenomegaly, and constitutional symptoms. Blood counts: Neutrophils ≥ 1,500/μL; Platelets \>100,000μL; Hemoglobin \> 11.0g/dL. Bone marrow normocellular for age, less than 30% of nucleated cells = lymphocytes. Lymphoid nodules absent. CRi= Fulfills CR but anemia or thrombocytopenia or neutropenia related to drug toxicity. PR= 2 criteria from group A and 1 from Group B. Group A: Decrease in the number of blood lymphocytes of 50% or more. Reduction in lymphadenopathy. No increase in any lymph node, and no new enlarged lymph node. A decrease in liver by at least 50% from baseline. Decrease in the size of the spleen by 50% or more. Reduction in marrow infiltrate or B-lymphoid nodules. Group B: Platelet counts \> than 100,000/μL or 50% better. Hemoglobin \> than 11.0g/dL or 50% better. Neutrophils\>1500/μL or 50% better. Criteria is continued in Analysis Population Description below...

  Range of responses between 8 weeks from initiation of treatment to 2 months post-treatment.

Secondary Outcomes (4)

• Survival Rates

  Up to 5 years

• Treatment Toxicity as Measured by Adverse Events Experienced While on Treatment

  Weeks 1, 3, 5, 7, 9, 11, 13, 15, and 17

• Correlation of Disease Characteristics With Disease Outcomes

  At baseline and over 18 weeks

• Compare Efficacy Between This Study and Historical Control Study of Alemtuzumab-rituximab

  At baseline and over 18 weeks

Study Arms (1)

Treatment (monoclonal antibody therapy)

EXPERIMENTAL

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

Biological: alemtuzumab; Biological: ofatumumab; Procedure: biopsy

Interventions

alemtuzumab BIOLOGICAL

Given SC

Also known as: anti-CD52 monoclonal antibody, Campath-1H, MoAb CD52, Monoclonal Antibody Campath-1H, Monoclonal Antibody CD52

Treatment (monoclonal antibody therapy)

ofatumumab BIOLOGICAL

Given IV

Also known as: Arzerra, HuMax-CD20

Treatment (monoclonal antibody therapy)

biopsy PROCEDURE

Correlative studies

Also known as: biopsies

Treatment (monoclonal antibody therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• Northwestern University: lead
• GlaxoSmithKline: collaborator
• National Comprehensive Cancer Network: collaborator

Study Sites (2)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Karolinska University Hospital Solna

Stockholm, Sweden

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Alemtuzumab; ofatumumab; Biopsy

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Limitations and Caveats

The participating site (Karolinska University Hospital Solna) did not meet the total accrual goal. However, the lead site (Northwestern University) did.

Results Point of Contact

• Title: Shuo Ma, MD, PhD
• Organization: Northwestern University

shuo-ma@northwestern.edu

312-908-5250

Study Officials

• Shuo Ma, MD, PhD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 16, 2011
• First Posted: May 27, 2011
• Study Start: June 1, 2011
• Primary Completion: August 17, 2015
• Study Completion (Estimated): May 1, 2027
• Last Updated: May 23, 2025
• Results First Posted: January 22, 2021

Record last verified: 2025-05

Locations

SE (1); US (1)