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

NCT00565981 | Completed Phase 2 DMC

• 1 other identifier: FLUSALEM
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

B-cell Chronic Lymphocytic Leukemia

Keywords

B-CLL; refractory; molecular profiling; alemtuzumab; fludarabinephosphate

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (5)

• 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

Study Arms (1)

Overall study

EXPERIMENTAL

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; Drug: Alemtuzumab

Interventions

Fludarabine phosphate DRUG

orally, 40 mg/m2 d1-3 q4w, x4 cycles

Also known as: Fludara®

Overall study

Alemtuzumab DRUG

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

Also known as: MabCampath®

Overall study

Eligibility Criteria

• Age: 19 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients with CD23+, CD5+, CD19+, light chain monoclonal B CLL
• st 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Arbeitsgemeinschaft medikamentoese Tumortherapie: lead
• Schering-Plough: collaborator

Study Sites (8)

Landeskrankenhaus Feldkirch

Feldkirch, A-6806, Austria

Location

A.ö. Landeskrankenhaus Fürstenfeld

Fürstenfeld, A-8280, Austria

Location

Universitätsklinik Innsbruck/ Klinik für Innere Medizin

Innsbruck, A-6020, Austria

Location

A.ö. Landeskrankenhaus Leoben

Leoben, A-8700, Austria

Location

Krankenhaus der Stadt Linz

Linz, A-4020, Austria

Location

St. Johanns LK

Salzburg, A-5020, Austria

Location

A.ö. Krankenhaus der Landeshauptstadt St. Pölten

Sankt Pölten, A-3100, Austria

Location

Klinikum Kreuzschwestern Wels GmbH

Wels, A-4600, Austria

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

fludarabine phosphate; Alemtuzumab

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

Study Officials

• Richard Greil, MD

  IIIrd Medical Department for Hematology, Oncology, Rheumatology, Infectiology and Hemostasiology at the Medical University of Salzburg

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 29, 2007
• First Posted: November 30, 2007
• Study Start: March 1, 2004
• Primary Completion: February 13, 2008
• Study Completion: February 13, 2008
• Last Updated: December 7, 2017

Record last verified: 2017-12

Locations

AU (8)