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

Sponsors and Collaborators:	Arbeitsgemeinschaft medikamentoese Tumortherapie Schering-Plough
Information provided by:	Arbeitsgemeinschaft medikamentoese Tumortherapie
ClinicalTrials.gov Identifier:	NCT00565981

Purpose

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.

Condition	Intervention	Phase
B-Cell Chronic Lymphocytic Leukemia	Drug: Fludarabine phosphate Drug: Alemtuzumab	Phase II

MedlinePlus related topics: Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Fludarabine Fludarabine monophosphate Alemtuzumab Campath

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	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

Further study details as provided by Arbeitsgemeinschaft medikamentoese Tumortherapie:

Primary Outcome Measures:

Safety and tolerability [ Time Frame: within the duration of study ] [ Designated as safety issue: Yes ]
Complete and overall response rate [ Time Frame: within the duration of study ] [ Designated as safety issue: Yes ]
Infections grade III, IV [ Time Frame: within the duration of study ] [ Designated as safety issue: Yes ]
Rate of CMV reactivation [ Time Frame: within the duration of study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Time to retreatment [ Time Frame: within duration of trial ] [ Designated as safety issue: No ]
Overall survival [ Time Frame: within duration of trial ] [ Designated as safety issue: No ]
Response in lymphatic compartments [ Time Frame: within duration of trial ] [ Designated as safety issue: No ]
Molecular response/ immunologic MRD response [ Time Frame: within duration of trial ] [ Designated as safety issue: No ]
Quality of Life [ Time Frame: within duration of trial ] [ Designated as safety issue: No ]

Estimated Enrollment:	28
Study Start Date:	March 2004
Estimated Study Completion Date:	December 2008
Primary Completion Date:	October 2007 (Final data collection date for primary outcome measure)

Intervention Details:

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

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

Eligibility

Ages Eligible for Study:	19 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00565981

Locations

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

Sponsors and Collaborators

Arbeitsgemeinschaft medikamentoese Tumortherapie

Schering-Plough

Investigators

Principal Investigator:

Richard Greil, MD

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

More Information

Responsible Party:	Arbeitsgemeinschaft medikamentoese Tumortherapie ( Prof. Dr. Richard Greil )
Study ID Numbers:	FLUSALEM
Study First Received:	November 29, 2007
Last Updated:	June 4, 2008
ClinicalTrials.gov Identifier:	NCT00565981
Health Authority:	Austria: Agency for Health and Food Safety; Austria: Ethikkommission

Keywords provided by Arbeitsgemeinschaft medikamentoese Tumortherapie:

B-CLL
refractory
molecular profiling
alemtuzumab
fludarabinephosphate

Study placed in the following topic categories:

Chronic lymphocytic leukemia
Lymphatic Diseases
Leukemia
Leukemia, Lymphoid
Immunoproliferative Disorders
Leukemia, Lymphocytic, Chronic, B-Cell

Alemtuzumab
Leukemia, B-cell, chronic
Fludarabine
Fludarabine monophosphate
Lymphoproliferative Disorders
Leukemia, B-Cell

Additional relevant MeSH terms:

Antimetabolites
Neoplasms
Antimetabolites, Antineoplastic
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Immunologic Factors

Immune System Diseases
Antineoplastic Agents
Therapeutic Uses
Physiological Effects of Drugs
Immunosuppressive Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009