A Pilot Trial With Subcutaneous Alemtuzumab and Oral Fludarabinephosphate for the Determination of Safety, Efficacy and Molecular Profiling for the Prediction of Response

Subcutaneous MabCampath® (Alemtuzumab) and Oral Fludara® (Fludarabinephosphate) for the Treatment of Refractory or Relapsed Chronic Lymphocytic Leukemia in 2nd or 3rd Line of Treatment: A Pilot Trial (FLUSALEM) for the Determination of Safety, Efficacy and Molecular Profiling for the Prediction of Response

Open label multicenter, two-step, non-randomized (pilot) study to analyze the safety of 4 cycles of 3-day 40mg/m2 oral fludarabine with simultaneous thrice weekly application of 30mg alemtuzumab s.c. in patients with B-CLL disease in 1st and 2nd relapse after any primary treatment or with disease refractory to any therapy in 1st or 2nd line (including Fludarabine, ). This regimen is preceded by an escalation phase with 3-10-30 mg of alemtuzumab s.c.

After the first phase (completed treatment of 7 patients) an interim analysis of safety and efficacy will be performed. In case of a sufficient risk benefit assessment followed by the enrollment of further 21 patients. Final analysis of safety and preliminary efficacy will be based on all patients enrolled.

Study Overview

• Status: Completed
• Conditions: B-cell Chronic Lymphocytic Leukemia
• Intervention / Treatment: Drug: Fludarabine phosphate; Drug: Alemtuzumab

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Feldkirch, Austria, A-6806
    • Landeskrankenhaus Feldkirch
  • Fürstenfeld, Austria, A-8280
    • A.ö. Landeskrankenhaus Fürstenfeld
  • Innsbruck, Austria, A-6020
    • Universitätsklinik Innsbruck/ Klinik für Innere Medizin
  • Leoben, Austria, A-8700
    • A.ö. Landeskrankenhaus Leoben
  • Linz, Austria, A-4020
    • Krankenhaus der Stadt Linz
  • Salzburg, Austria, A-5020
    • St. Johanns LK
  • St. Poelten, Austria, A-3100
    • A.ö. Krankenhaus der Landeshauptstadt St. Pölten
  • Wels, Austria, A-4600
    • Klinikum Kreuzschwestern Wels GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female patients with CD23+, CD5+, CD19+, light chain monoclonal B CLL
• 1st or 2nd relapse after fludarabine or any other primary treatment regimen or refractory to primary or secondary treatment (including fludarabine) and simultaneously indication for treatment according to the NCI Workshop Criteria 1996
• Age 19-75
• WHO performance score 0-2
• Informed consent given by the patient

Exclusion Criteria:

• HIV positive or positive for Hepatitis B or C
• active uncontrolled infection
• child bearing age without adequate control of fertility, pregnant or lactating women
• intolerance towards any ingredient of either oral fludarabine or alemtuzumab
• allergy against foreign proteins
• previous treatment with alemtuzumab
• treatment with an experimental drug within the previous 2 months
• second malignant disease (non CLL)
• CLL in transformation (Richter syndrome)
• decreased kidney-function with creatinine-clearance < 30ml/min
• severe concomitant diseases or major organ dysfunctions
• patients who are unable to comply with the requirements of the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Overall study; The FLUSALEM protocol combines 4 cycles of oral fludarabine phosphate (40mg/m² d1-3; q 29d) and an intensive dose schedule of alemtuzumab (30mg sc.3 times weekly for 16 weeks) in an outpatient setting	Drug: Fludarabine phosphate; orally, 40 mg/m2 d1-3 q4w, x4 cycles; Other Names: Fludara®; Drug: Alemtuzumab; subcutaneous, starting dose 3 mg and escalation to 10 mg, then 30 mg, followed by 30 mg thrice weekly for 16 weeks in escalated dose; Other Names: MabCampath®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability	within the duration of study
Complete and overall response rate	within the duration of study
Infections grade III, IV	within the duration of study
Rate of CMV reactivation	within the duration of study

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to retreatment	within duration of trial
Overall survival	within duration of trial
Response in lymphatic compartments	within duration of trial
Molecular response/ immunologic MRD response	within duration of trial
Quality of Life	within duration of trial

Collaborators and Investigators

• Sponsor: Arbeitsgemeinschaft medikamentoese Tumortherapie
• Collaborators: Schering-Plough
• Investigators: Principal Investigator: Richard Greil, MD, IIIrd Medical Department for Hematology, Oncology, Rheumatology, Infectiology and Hemostasiology at the Medical University of Salzburg

Study record dates

Study Major Dates

• Study Start: March 1, 2004
• Primary Completion (Actual): February 13, 2008
• Study Completion (Actual): February 13, 2008

Study Registration Dates

• First Submitted: November 29, 2007
• First Submitted That Met QC Criteria: November 29, 2007
• First Posted (Estimate): November 30, 2007

Study Record Updates

• Last Update Posted (Actual): December 7, 2017
• Last Update Submitted That Met QC Criteria: December 6, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: refractory; B-CLL; alemtuzumab; molecular profiling; fludarabinephosphate
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Fludarabine; Fludarabine phosphate; Alemtuzumab
• Other Study ID Numbers: FLUSALEM