Phase 2 Fludarabine, Cytoxan and FCCAM <Alemtuzumab> in Untreated B-Cell Chronic Lymphocytic Leukemia

NCT00230282 | Completed Phase 2 Results DMC

• 4 other identifiers: IRB-130533118580071HEMCLL0001
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study was to evaluate the safety and efficacy of the combination of fludarabine and cyclophosphamide in previously untreated CLL patients. Participants will receive fludarabine and cyclophosphamide on days 1, 2, and 3 of six 28-day cycles.

Conditions

Leukemia; B-cell Leukemia; Chronic Leukemia; Chronic Lymphocytic Leukemia (CLL)

Outcome Measures

Primary Outcomes (1)

• Number of Subjects Maintaining Partial Response (PR) or Complete Response (CR)

  Response criteria as per the NCI-WG Revised Guidelines for B-CLL Complete remission: No lymphadenopathy by physical exam No hepatomegaly or splenomegaly Absence of constitutional symptoms Polymorphonuclear leukocytes \> 1,500/uL, Platelets \> 100,000/uL, Hemoglobin \> 11.0 g/dL Bone marrow aspirate and biopsy normocellular with \< 30% lymphocytes Absent lymphoid nodules Partial remission: * 50% decrease in peripheral blood lymphocyte count from the pretreatment baseline value * 50% reduction in lymphadenopathy and/or ≥ 50% reduction in the size of the liver and/or spleen AND one or more of the following Polymorphonuclear leukocytes \> 1,500/uL or 50% improvement over baseline Platelets \> 100,000/uL or 50% improvement over baseline Hemoglobin \> 11.0 g/dL or 50% improvement over baseline

  24 weeks

Secondary Outcomes (1)

• Duration of Response

  105 months

Study Arms (1)

Fludarabine, cytoxan, then alemtuzumab

EXPERIMENTAL

Fludarabine and cyclophosphamide days 1 to 3 for six 28-day cycles. Minimal residual disease positive responders continued on-treatment to receive alemtuzumab 30 mg weekly. MRD negative responders were observed.

Drug: Alemtuzumab; Drug: Fludarabine; Drug: Cytoxan

Interventions

Alemtuzumab DRUG

3 to 30 mg, IV

Also known as: Campath, MabCampath, Campath-1H, Lemtrada, FCCam

Fludarabine, cytoxan, then alemtuzumab

Fludarabine DRUG

\[(2R,3R,4S,5R)-5-(6-amino-2-fluoro-purin-9-yl)- 3,4-dihydroxy-oxolan-2-yl\]methoxyphosphonic acid

Also known as: Fludara

Fludarabine, cytoxan, then alemtuzumab

Cytoxan DRUG

(RS)-N,N-bis(2-chloroethyl)-1,3,2-oxazaphosphinan-2-amine 2-oxide

Also known as: Cyclophosphamide, cytophosphane, Endoxan, Neosar, Procytox, Revimmune

Fludarabine, cytoxan, then alemtuzumab

Eligibility Criteria

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

You may qualify if:

• ≥ age 18
• Karnofsky performance status 60% or above
• Confirmed immunohistological diagnosis of Chronic Lymphocytic Leukemia (CLL)
• Rai Stage I to IV as follows:
• Advanced stage disease (Rai Stage III or IV, or modified Rai High Risk)
• Patients with Rai Stage I - II or (Modified Rai Intermediate-Risk) disease must have an indication for therapy based on 1996 NCI revised criteria for active disease as follows:
• Any one of the following disease-related symptoms:
• Weight loss ≥ 10% body weight within the previous 6 months
• Extreme fatigue
• Fever greater than 100.5° F for ≥ 2 weeks without evidence of infection
• Night sweats without evidence of infection
• Evidence of progressive marrow failure based on the development of worsening of anemia or thrombocytopenia
• Autoimmune anemia and/or thrombocytopenia poorly responsive to corticosteroid therapy
• Massive (\> 6 cm below the left costal margin) or progressive splenomegaly
• Bulky (\>10 cm in cluster) or progressive lymphadenopathy

You may not qualify if:

• Prior pharmacological treatment for CLL
• Past history of anaphylaxis following exposure to monoclonal antibodies
• Active secondary malignancy or a history of malignant disease (other than CLL or non-melanoma skin cancer) within the preceding 5 years
• Any medical condition requiring systemic corticosteroids
• Active systemic infection
• Major systemic or other illness (including Coombs positivity and active hemolysis) that would, in the opinion of the investigator, interfere with the patient's ability to comply with the protocol, compromise patient safety, or interfere with the interpretation of study results
• HIV positive by serologic testing
• Pregnant or nursing female
• Unwilling/unable to practice an acceptable form of contraception.

Sponsors & Collaborators

• Steven E. Coutre: lead
• Bayer: collaborator

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Leukemia; Leukemia, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Alemtuzumab; fludarabine; fludarabine phosphate; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; 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; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Steven E. Coutre, Associate Professor of Medicine
• Organization: Stanford University

coutre@stanford.edu

650-723-6661

Study Officials

• Steven Edward Coutre

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: September 28, 2005
• First Posted: September 30, 2005
• Study Start: July 1, 2004
• Primary Completion: December 1, 2010
• Study Completion: October 1, 2011
• Last Updated: October 6, 2014
• Results First Posted: September 8, 2014

Record last verified: 2014-09

Locations

US (1)