Fludarabine, Rituximab, and Alemtuzumab in Treating Patients With Chronic Lymphocytic Leukemia

NCT00098670 | Completed Phase 2 Results

• 5 other identifiers: NCI-2012-02812CDR0000398139CALGB-10101P30CA014236U10CA031946
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial is studying how well giving fludarabine together with rituximab followed by alemtuzumab works in treating patients with chronic lymphocytic leukemia. Monoclonal antibodies, such as rituximab and alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others can find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving fludarabine together with rituximab followed by alemtuzumab may kill more cancer cells.

Conditions

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 (1)

• Number of Participants With a Complete Response After Treatment With Fludarabine & Rituximab Followed by Alemtuzumab

  A complete response, as defined by the National Cancer Institute Working Group (NCIWG): \- CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate \& biopsy

  Duration of treatment (up to 13.5 months)

Secondary Outcomes (4)

• Number of Participants With a Complete or Partial Response After Induction Therapy With Fludarabine & Rituximab

  Up to 9 months

• 2 Year Progression Free Survival

  2 years from registration

• 2 Year Survival

  2 years from registration

• Number of Participants With Severe Non-Hematologic Adverse Events During Treatment With Alemtuzumab

  6 weeks beginning at study week 36

Study Arms (1)

Treatment (alemtuzumab, rituximab, fludarabine phosphate)

EXPERIMENTAL

Patients receive induction therapy comprising rituximab IV over 4 hours on days 1, 3, and 5 of course 1 and day 1 of all subsequent courses and fludarabine IV over 30 minutes on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression. Approximately 4 months after completion of induction therapy, patients achieving a partial response, nodular partial response, or stable disease receive consolidation therapy comprising alemtuzumab subcutaneously on days 1-3. Treatment repeats weekly for up to 6 courses in the absence of disease progression.

Biological: alemtuzumab; Biological: rituximab; Drug: fludarabine phosphate

Interventions

alemtuzumab BIOLOGICAL

Given SC

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

Treatment (alemtuzumab, rituximab, fludarabine phosphate)

rituximab BIOLOGICAL

Given IV

Also known as: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan

Treatment (alemtuzumab, rituximab, fludarabine phosphate)

fludarabine phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, Fludara

Treatment (alemtuzumab, rituximab, fludarabine phosphate)

Eligibility Criteria

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

You may qualify if:

• Specific Diagnosis of B-Cell CLL
• An absolute lymphocytosis of \> 5,000/μL
• Morphologically, the lymphocytes must appear mature with \< 55% prolymphocytes
• Bone marrow examination must include at least a unilateral aspirate and biopsy; the aspirate smear must show \> 30% of all nucleated cells to be lymphoid or the bone marrow core biopsy must show lymphoid infiltrates compatible with marrow involvement by CLL; the overall cellularity must be normocellular or hypercellular
• Local institution lymphocyte phenotype must reveal a predominant B-cell monoclonal population sharing a B-cell marker (CD19, CD20, CD23) with the CD5 antigen, in the absence of other pan-T-cell markers; additionally, the B-cells must be monoclonal with regard to expression of either κ or λ and have surface immunoglobulin expression of low density; patients with bright surface immunoglobulin levels must have CD23 co-expression
• Patients must be in the intermediate- or high-risk categories of the modified three-stage Rai staging system (i.e., stages I, II, III, or IV)
• Patients in the intermediate-risk group must have evidence of active disease as demonstrated by at least one of the following criteria:
• Massive or progressive splenomegaly, hepatomegaly and/or lymphadenopathy;
• Presence of weight loss \> 10% over the preceding 6 month period;
• Grade 2 or 3 fatigue;
• Fevers \> 100.5°F or night sweats for greater than 2 weeks without evidence of infection;
• Progressive lymphocytosis with an increase of \> 50% over a 2 month period or an anticipated doubling time of less than 6 months
• No prior therapy for CLL including corticosteroids for autoimmune complications that have developed since the initial diagnosis of CLL
• No medical condition requiring chronic use of oral corticosteroids
• Performance Status 0 - 2

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Cancer and Leukemia Group B

Chicago, Illinois, 60606, United States

Location

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• Jones JA, Ruppert AS, Zhao W, Lin TS, Rai K, Peterson B, Larson RA, Marcucci G, Heerema NA, Byrd JC. Patients with chronic lymphocytic leukemia with high-risk genomic features have inferior outcome on successive Cancer and Leukemia Group B trials with alemtuzumab consolidation: subgroup analysis from CALGB 19901 and CALGB 10101. Leuk Lymphoma. 2013 Dec;54(12):2654-9. doi: 10.3109/10428194.2013.788179. Epub 2013 May 9.

  PMID: 23547837 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Alemtuzumab; Rituximab; fludarabine phosphate

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; Antibodies, Monoclonal, Murine-Derived

Results Point of Contact

• Title: Dr. Thomas Lin
• Organization: The Ohio State University

thomas.lin@osumc.edu

Study Officials

• Thomas Lin

  Cancer and Leukemia Group B

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: December 7, 2004
• First Posted: December 8, 2004
• Study Start: October 1, 2004
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: May 21, 2014
• Results First Posted: December 3, 2012

Record last verified: 2012-12

Locations

US (2)