A Phase II Trial of Alemtuzumab and Rituximab in Patients With Previously Untreated CLL

NCT00858117 | Completed Phase 2 Results DMC

• 2 other identifiers: NU 04H6STU00004494
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Monoclonal antibodies, such as alemtuzumab and 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 alemtuzumab together with rituximab may kill more cancer cells. PURPOSE: This phase II trial is studying the side effects of giving alemtuzumab together with rituximab and to see how well it works in treating patients with previously untreated B-cell chronic lymphocytic leukemia.

Conditions

Leukemia

Keywords

B-cell chronic lymphocytic leukemia; stage I chronic lymphocytic leukemia; stage II chronic lymphocytic leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia

Outcome Measures

Primary Outcomes (2)

• Number of Patients Treated With Alemtuzumab and Rituximab Combination With a Response (CR or PR) Assessed by NCI-WG 1996 Criteria With Lymph-adenopathy and Organomegaly Measured During Physical Examination

  Response rate (complete remission(CR) + partial remission(PR)) will be, assessed by NCI-WG 1996 criteria with lymphadenopathy and organomegaly measured during physical examination. CR=Absence of lymphadenopathy and constitutional symptoms, Normal CBC (leukocytes ≥ 1500/μl, Platelets \>100,000/μl, Hemoglobin \> 11.0 gm/dl), peripheral blood lymphocytes ≤ 4,000/μl.The marrow sample must be at least normocellular with \< 30% of nucleated cells being lymphocytes. PR=absence of constitutional symptoms, ≥ 50% decrease in peripheral blood lymphocyte count from the pretreatment baseline value, ≥ 50% reduction in lymphadenopathy, ≥ 50% reduction in size of liver and/or spleen and one of the following: polymorphonuclear leukocytes ≥ 1,500/μl or 50% improvement over baseline platelets \> 100,000/μl or 50% improvement over baseline or hemoglobin \> 11.0 gm/dl or 50% improvement over baseline without transfusions

  At week 9, and post-18 weeks then every 3 months for a year and up every 6 months for up to 2 years

• Number of Patients Treated With Alemtuzumab and Rituximab Combination With Response (CR or PR) Assessed by NCI-WG 1996 Criteria With Measurements of the Lymph Nodes and Spleen Size by CT Scans

  Response rate (complete remission(CR) + partial response(PR)) will be assessed by NCI-WG 1996 criteria with measurements of the lymph nodes and spleen size by CT scans. Best response at any timepoint is captured below. CR= absence of significant lymphadenopathy (e.g. lymph nodes \> 1.5 cm in their greatest transverse diameter) and no hepatomegaly or splenomegaly. PR=reduction in lymphadenopathy as defined by the following: (a) a decrease in lymph node size by 50% or more either in the sum products of up to six lymph nodes, or in the largest diameter of the enlarged lymph node(s) detected prior to therapy; (b) no increase in any lymph node, and no new enlarged lymph node; in small lymph nodes (\< 2cm), an increase of less than 25% was not considered to be significant and a reduction in the noted pretreatment enlargement of the spleen or liver by 50% or more.

  At week 9, and post-18 weeks then every 3 months for a year and up every 6 months for up to 2 years

Secondary Outcomes (1)

• Toxicity of the Study Medications, Alemtuzumab and Rituximab

  During treatment, 18 weeks

Study Arms (1)

Alemtuzumab and Rituximab

EXPERIMENTAL

Administration of Alemtuzumab combined with Rituximab to test the feasibility of combining these two monoclonal antibodies as a first line therapy in patients with B-cell chronic lymphocytic leukemia.

Biological: Alemtuzumab; Biological: Rituximab

Interventions

Alemtuzumab BIOLOGICAL

Alemtuzumab administered subcutaneously 30mg per day, 3 days per week for 18 weeks

Also known as: Campath-1H

Alemtuzumab and Rituximab

Rituximab BIOLOGICAL

Rituximab administered intravenously at 375mg/m2 every 2 weeks for 18 weeks

Also known as: Rituxan

Alemtuzumab and Rituximab

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Diagnosis of B-cell chronic lymphocytic leukemia (CLL)\*, as defined by the following criteria: * Peripheral blood absolute lymphocyte count \> 5,000/mm³ * Small- to moderate-size lymphocytes with \< 55% prolymphocytes, atypical lymphocytes, or lymphoblasts * Phenotypically characterized B-CLL expressing CD20 and CD52, as defined by the following: * Predominant population of cells share B-cell antigens with CD-5 in the absence of other pan-T-cell markers (e.g., CD-3, CD-2) * B-cell expresses either lambda or kappa light chains * Surface immunoglobulin with low-cell surface density expression NOTE: \*Presence of splenomegaly, hepatomegaly, or lymphadenopathy are not required for the diagnosis of CLL * Requires therapy, as indicated by ≥ 1 of the following criteria: * Unintentional weight loss \> 10% within the past 6 months * Extreme fatigue (i.e., ECOG performance status 2) * Fevers \> 100.5°F for 2 weeks without evidence of infection * Night sweats without evidence of infection * Evidence of progressive marrow failure as manifested by the development of or worsening of anemia (hemoglobin \< 10 g/dL) and/or thrombocytopenia (platelet count \< 100,000/mm³) * Massive (i.e., \> 6 cm below left costal margin) or progressive splenomegaly * Massive nodes/clusters (\> 5 cm), progressive symptomatic adenopathy, or adenopathy resulting in end-organ damage * Progressive lymphocytosis with an increase of \> 50% over 2 months or an anticipated doubling time \< 6 months * 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 eligibility PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * ANC ≥ 1,000/mm³\* * Platelet count ≥ 50,000/mm³\* * Hemoglobin ≥ 10 g/dL\* * Serum creatinine ≤ 2.0 mg/dL OR creatinine clearance \> 40 mL/min * Bilirubin \< 2 mg/dL * AST and ALT ≤ 2 times normal (unless secondary to tumor infiltration/lymphadenopathy) * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 6 months after completion of study treatment * No active autoimmune anemia or thrombocytopenia * No active infection requiring oral or intravenous antibiotics * No second malignancy, other than basal cell carcinoma of the skin or in situ carcinoma of the cervix, unless curatively treated ≥ 2 years ago NOTE: \*If cytopenias are due to degree of bone marrow involvement, patient may be eligible at the discretion of the principal investigator. PRIOR CONCURRENT THERAPY: * Prior corticosteroid therapy allowed * No prior cytotoxic therapy (other than corticosteroids)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Northwestern University: lead
• Bayer: collaborator

Study Sites (1)

Northwestern University, Northwestern Medical Faculty Foundation

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Alemtuzumab; Rituximab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; 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; Antibodies, Monoclonal, Murine-Derived

Results Point of Contact

• Title: Olga Frankfurt, MD
• Organization: Northwestern University

o-frankfurt@northwestern.edu

312 695 6180

Study Officials

• Olga Frankfurt, MD

  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: SPONSOR

Study Record Dates

• First Submitted: March 6, 2009
• First Posted: March 9, 2009
• Study Start: September 26, 2005
• Primary Completion: March 17, 2010
• Study Completion: January 24, 2013
• Last Updated: November 6, 2020
• Results First Posted: October 19, 2020

Record last verified: 2020-10

Locations

US (1)