Alemtuzumab and Rituximab in Treating Patients With High-Risk, Early-Stage Chronic Lymphocytic Leukemia

NCT00436904 | Completed Phase 2 Results DMC

• 6 other identifiers: CDR0000529809P30CA015083MC038G801-04106.G0309U3023s
• 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 and how well giving alemtuzumab together with rituximab works in treating patients with high-risk, early-stage chronic lymphocytic leukemia.

Conditions

Leukemia

Keywords

stage 0 chronic lymphocytic leukemia; stage I chronic lymphocytic leukemia; stage II chronic lymphocytic leukemia; B-cell chronic lymphocytic leukemia

Outcome Measures

Primary Outcomes (2)

• Confirmed Response, Defined as Objective Complete Remission or Partial Remission for a Duration of at Least 2 Months

  Confirmed response is defined as a \> 50% decrease in clinical symptoms from baseline and recovery from blood counts.

  Up to 6 months

• Number of Participants With Treatment Related Adverse Events

  Adverse events (AE) that are classified as either possibly, probably, or definitely related to study treatment according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE version 3.0). The maximum grade for each type of AE will be recorded for each patient. Grade refers to the severity of the AE.\> \> Grade 1: Mild AE, Grade 2: Moderate AE, Grade 3: Severe AE, Grade 4: Life-threatening or disabling AE, Grade 5: Death related AE

  Weekly for first 6 weeks, then monthly for 6 months, then at 9 and 12 months post registration

Secondary Outcomes (4)

• Time to Response

  Registration to first response (up to 5 years)

• Duration of Response

  Up to 5 years

• Survival

  Death or last follow-up (up to 5 years)

• Time to Disease Progression

  Time from registration to progression (up to 5 years)

Study Arms (1)

Alemtuzumab + Rituximab

EXPERIMENTAL

Alemtuzumab 30mg Monday, Wednesday, and Friday x 5 weeks, Rituximab 375/mg/m2 IV weekly (Wednesday) x 4 weeks (weeks 2-5)

Drug: Alemtuzumab; Drug: Rituximab

Interventions

Alemtuzumab DRUG

30 mg Monday, Wednesday, and Friday x 5 weeks

Alemtuzumab + Rituximab

Rituximab DRUG

375mg/m2 IV weekly (Wednesday) x 4 weeks (weeks 2-5)

Alemtuzumab + 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) \- Early-stage, biologically high-risk disease defined by the following criteria: * Rai stage 0-II (does not meet standard NCI-sponsored Working Group criteria for treatment) * Clinical and phenotypic features manifested in the peripheral blood, including the following: * Minimum threshold peripheral blood lymphocyte count of \> 5,000/mm³ * Small-to-moderate peripheral blood lymphocytes with ≤ 55% prolymphocytes * Monoclonality of B lymphocytes by immunophenotypic evaluation, demonstrating co-expression of CD19, CD5, and CD23 antigens, surface expression of CD20 and CD52, and B-cell monoclonal population defined by light-chain exclusions * Poor prognosis demonstrated by ≥ 1 of the following high-risk parameters: * Unmutated human immunoglobulin variable region heavy chain (IgVH) gene and CD38 expression (≥ 30% cells positive on flow cytometry) OR unmutated IgVH ZAP-70 expression (≥ 20% cells positive on flow cytometry) = 11q- = 17p- PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Creatinine ≤ 1.5 times upper limit of normal (ULN) * Total bilirubin ≤ 3.0 times ULN OR direct bilirubin ≤ 1.5 times ULN * AST ≤ 3.0 times ULN (unless due to hemolysis or CLL) * Hemoglobin ≥ 9.0 g/dL * No New York Heart Association class III-IV heart disease * No myocardial infarction within the past month * No uncontrolled infection * No active HIV infection * No evidence of autoimmune hemolytic anemia, immune thrombocytopenia, or pure red blood cell aplasia * No other active primary malignancy requiring treatment or limiting survival to less than 2 years PRIOR CONCURRENT THERAPY: * No prior treatment for CLL * Prior corticosteroids allowed * No prior radiotherapy * More than 4 weeks since prior major surgery

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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (2)

• Zent CS, Call TG, Shanafelt TD, Tschumper RC, Jelinek DF, Bowen DA, Secreto CR, Laplant BR, Kabat BF, Kay NE. Early treatment of high-risk chronic lymphocytic leukemia with alemtuzumab and rituximab. Cancer. 2008 Oct 15;113(8):2110-8. doi: 10.1002/cncr.23824.

  PMID: 18759253 RESULT

• Zent CS, Secreto CR, LaPlant BR, Bone ND, Call TG, Shanafelt TD, Jelinek DF, Tschumper RC, Kay NE. Direct and complement dependent cytotoxicity in CLL cells from patients with high-risk early-intermediate stage chronic lymphocytic leukemia (CLL) treated with alemtuzumab and rituximab. Leuk Res. 2008 Dec;32(12):1849-56. doi: 10.1016/j.leukres.2008.05.014. Epub 2008 Jun 27.

  PMID: 18584865 RESULT

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: Dr. Clive Zent
• Organization: Mayo Clinic

zent.clive@mayo.edu

507-284-5362

Study Officials

• Clive S. Zent, MD

  Mayo Clinic

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2007
• First Posted: February 19, 2007
• Study Start: December 1, 2004
• Primary Completion: July 1, 2008
• Study Completion: November 1, 2011
• Last Updated: December 1, 2011
• Results First Posted: October 26, 2011

Record last verified: 2011-11

Locations

US (1)