Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Alemtuzumab

Ofatumumab

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Immunologic Factors

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.

alemtuzumab

ofatumumab

biopsy

Shuo Ma, MD, PhD

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

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.

Alemtuzumab-Ofatumumab in Previously Untreated Symptomatic Chronic Lymphocytic Leukemia

A Phase 2 Trial of Alemtuzumab-Ofatumumab Combination in Previously Untreated Symptomatic Chronic Lymphocytic Leukemia

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...

Survival rates will be calculated for progression-free survival (PFS), therapy-free survival (TFS), and overall survival (OS).

Clinical outcomes (such as response, PFS and TFS) will be correlated with pre-treatment clinical and biological characteristics(such as Rai staging, presence of bulky lymph nodes, cytogenetics by FISH, CD38, ZAP70 and IgVH mutation status).

Response and survival rates will be compared between the two studies.

GlaxoSmithKline

National Comprehensive Cancer Network

Northwestern University

Principal Investigator

Alemtuzumab: Administered subcutaneously, 3 times per week for up to 18 weeks at a standard dose of 30mg (except for week 1 which will dose escalate from 3mg→10mg→30mg).

Ofatumumab: Starting at week 3, administered intravenously on day 1 of every other week prior to alemtuzumab for a total of 8 doses. For week 3 (dose 1) ofatumumab will be given at a dose of 300mg; for weeks 5, 7, 9, 11, 13, 15, and 17 (doses 2-8) ofatumumab will be given at a dose of 2000mg.

Toxicity was assessed after completion of the extended safety run-in period of the first 12 patients at an ofatumumab dose of 2000 mg for doses 2-8. Depending on the number of patients who experienced a dose limiting toxicity in the initial 2 safety cohorts, ofatumumab doses 2-8 could have been continued at 2000 mg or reduced to 1000 mg for subsequent patients. Based on the toxicity data of the first 12 patients, ofatumumab doses 2-8 were given at 2000 mg for doses 2-8 for all patients.

Based on experience with the initial safety run-in cohort of 6 patients, early stopping is necessary to avoid over-treatment in patients who have achieved a complete remission early. As soon as a patient is determined to have achieved MRD- CR or CRi (per iwCLL2008 criteria), both alemtuzumab and ofatumumab will be stopped.

Alemtuzumab + Ofatumumab

Alemtuzumab: Administered subcutaneously, 3 times per week for up to 18 weeks at a standard dose of 30mg (except for week 1 which will dose escalate from 3mg→10mg→30mg).

Ofatumumab: Starting at week 3, administered intravenously on day 1 of every other week prior to alemtuzumab for a total of 8 doses. For week 3 (dose 1) ofatumumab will be given at a dose of 300mg; for weeks 5, 7, 9, 11, 13, 15, and 17 (doses 2-8) ofatumumab will be given at a dose of 2000mg.

Toxicity was assessed after completion of the extended safety run-in period of the first 12 patients at an ofatumumab dose of 2000 mg for doses 2-8. Depending on the number of patients who experienced a dose limiting toxicity in the initial 2 safety cohorts, ofatumumab doses 2-8 could have been continued at 2000 mg or reduced to 1000 mg for subsequent patients. Based on the toxicity data of the first 12 patients, ofatumumab doses 2-8 were given at 2000 mg for doses 2-8 for all patients.

biopsy: Correlative studies

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Sweden

United States

Region of Enrollment

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

Complete Remission (CR), Minimal Residual Disease (MRD) Negative

Complete Remission (CR), Minimal Residual Disease (MRD) positive

Complete Remission, MRD status unknown

Complete Remission with Incomplete Marrow Recovery (CRi)

Partial Remission (PR)

Progressive Disease (PD)

Criteria from Outcome Measure Description cont. MRD=Bone marrow with less than one CLL cell per 10,000 leukocytes. To qualify as a PD: at least two of the criteria of in Group A, plus one of the criteria in Group B, must be met. Group A: An increase ≥ 50% of: lymphadenopathy, hepatomegaly, or splenomegaly. An increase ≥ 50% over baseline in blood lymphocytes. Group B: Platelet count decrease of ≥ 50% from baseline secondary to CLL, Hemoglobin decrease of \> 2g/dl from baseline secondary to CLL.

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

Survival Rates

Treatment Toxicity as Measured by Adverse Events Experienced While on Treatment

Correlation of Disease Characteristics With Disease Outcomes

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

Spots Global Cancer Trial Database for Alemtuzumab-Ofatumumab in Previously Untreated Symptomatic Chronic Lymphocytic Leukemia

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial