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

Steven E. Coutre

Status and phase: Completed; Phase 2

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

Treatments: Drug: Fludarabine; Drug: Alemtuzumab; Drug: Cytoxan

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00230282

31185 (Other Identifier)

80071 (Other Identifier)

IRB-13053

HEMCLL0001 (Other Identifier)

Details and patient eligibility

About

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.

Full description

This single-arm study evaluated the safety and efficacy of the combination of fludarabine 25 mg/m2/d IV and cyclophosphamide 250 mg/m2/d SC in previously untreated CLL patients. Participants received fludarabine and cyclophosphamide on days 1, 2, and 3 of six 28-day cycles, followed by a no-treatment rest period (observation) for 3 to 12 weeks.

Responders entered a no-treatment rest period (observation) for 3 to 8 weeks, then depending on status, continued on follow-up or on-study to receive Campath stating at 3 mg/day with the dose adjusted to the maximum tolerated dose.

Enrollment: 25 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• ≥ 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)

  • OR

  • 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:

      1. Weight loss ≥ 10% body weight within the previous 6 months
      2. Extreme fatigue
      3. Fever greater than 100.5° F for ≥ 2 weeks without evidence of infection
      4. 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

    • Progressive lymphocytosis > 50% increase over 2 months, or anticipated doubling time < 6 months

• Patients with immunoglobulin VH gene in unmutated nucleotide sequence configuration, as defined by ≥ 98% homology with the nearest germline counterpart

• Serum creatinine ≤ 2x the upper limit of normal

• Total serum bilirubin ≤ 2x the upper limit of normal.

• AST ≤ 2x the upper limit of normal.

• ALT ≤ 2x the upper limit of normal.

• Signed written informed consent

Exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

25 participants in 1 patient group

Fludarabine, cytoxan, then alemtuzumab

Experimental group

Description:

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.

Treatment:

Drug: Cytoxan

Drug: Alemtuzumab

Drug: Fludarabine