NCT01392079

Brief Summary

Aims and objectives

  • Assessment of the efficacy of the study treatment in the study population in terms of response rate, progression-free survival, failure-free survival and overall survival.
  • Acquisition of further data to expand the data base on the toxicity of the study treatment.
  • Assessment of the efficacy of the study treatment in biological risk groups.
  • Assessment of response in terms of minimal residual disease. Number of patients and estimated duration Total no. of patients: 122 (\~29 with 17p deletion for first-line therapy, \~29 with 17p deletion for second- or higher-line treatment, \~65 fludarabine-refractory irrespective of 17p status). Duration for each patient: Max. 12 weeks of treatment in three 4-week cycles, then up to two years maintenance treatment.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
135

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Feb 2008

Longer than P75 for phase_2

Geographic Reach
3 countries

38 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2008

Completed
3.4 years until next milestone

First Submitted

Initial submission to the registry

June 28, 2011

Completed
14 days until next milestone

First Posted

Study publicly available on registry

July 12, 2011

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2012

Completed
4.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2016

Completed
Last Updated

October 24, 2019

Status Verified

October 1, 2019

Enrollment Period

3.9 years

First QC Date

June 28, 2011

Last Update Submit

October 21, 2019

Conditions

Chronic Lymphocytic Leukemia

Keywords

CLL17p deletionrefractory to fludarabinesubcutaneous alemtuzumabCLL with 17p- or refractory to fludarabine

Outcome Measures

Primary Outcomes (1)

  • Response rate

    Time points for response evaluation according to NCI criteria will be: * The end of each treatment cycle: after 12 doses (4 weeks actual treatment), 24 doses (8 weeks actual treatment), and 36 doses (12 weeks actual treatment) of alemtuzumab * During maintenance therapy, every three months * During follow-up, every three months * A final response assessment will be made at the end of study treatment if the patient's participation is ended at a point other than one of those specified above.

    2.5 years

Secondary Outcomes (4)

  • Progression-free-survival

    up to five years

  • Failure-free survival

    up to five years

  • Overall survival

    up to five years

  • Number of participants with Adverse Events as a measure of safety and tolerability

    up to 2.5 years

Study Arms (1)

Alemtuzumab

EXPERIMENTAL

30 mg alemtuzumab will be administered subcutaneously 3 times weekly for 4 weeks (total of 12 doses of 30 mg alemtuzumab) with premedication (as needed) and infection prophylaxis; combined with oral dexamethasone 40 mg total dose for 4 days every 2 weeks; evaluation at end of cycle (i.e. after 12 doses of 30 mg alemtuzumab). If CR is documented after week 4 (12 doses of 30 mg alemtuzumab) or 8 (24 doses of 30 mg alemtuzumab), maintenance treatment with alemtuzumab or withdrawal from the study and stem cell transplantation will be instituted at this time point. After a maximum of three 4-week cycles (total of 36 doses of 30 mg alemtuzumab, in case of interruptions this may take longer than 12 weeks), maintenance treatment with alemtuzumab or withdrawal from the study and stem cell transplantation will be instituted. Maintenance treatment with alemtuzumab will continue for a maximum of two years, with evaluation every three months, unless there is PD.

Drug: Alemtuzumab

Interventions

AlemtuzumabDRUG

Alemtuzumab 30 mg s.c. 3 × weekly for 28 days (Days 1, 3, 5; 8, 10, 12; etc.)

Alemtuzumab

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • The patient has CLL requiring treatment (Binet C or A/B with "active disease" according to the NCI criteria).
  • One or both of the following is true:
  • The patient's disease is refractory to a previous fludarabine-containing regimen, defined as no CR or PR according to NCI criteria, or progression within 6 months after a fludarabine-containing regime. (N.B.: Within the framework of this trial, the term "fludarabine-refractory" is synonymous to a refractory status to any established purine analogue (i.e. pentostatin, cladribine); this also encompasses bendamustine, as this drug molecule contains both an alkylating and a purine analogue moiety. Acc. to experimental findings and clinical experience, its mechanism of action differs distinctly from that of a pure alkylator (Cheson et al., 2009, Leoni et al., 2008)).
  • p deletion is present (irrespective of whether previously treated or untreated).
  • The patient is at least 18 years of age.
  • The patient's performance status is 0, 1 or 2 on the WHO/ECOG scale.
  • Any previous chemotherapy and/or immunotherapy ended at least four weeks before the first study treatment with alemtuzumab.
  • The patient has recovered from all previous chemotherapy and/or immunotherapy.
  • For fertile men and for women of childbearing potential: Adequate contraception (oral contraceptives, intrauterine device or barrier method in conjunction with spermicidal jelly).
  • The patient has given written informed consent to participate in the study.

You may not qualify if:

  • The patient has received more than five different prior therapeutic regimens.
  • Any major organ dysfunction is present (e.g. unstable angina pectoris, NYHA III/IV heart insufficiency, significant coronary stenoses, uncontrolled diabetes mellitus, uncontrolled hypertension, pulmonary disease with hypoxemia, renal failure).
  • Any of the following laboratory values are found at the screening visit to be \>2 × the upper limit of the normal range: serum creatinine, serum bilirubin, ASAT, ALAT.
  • Any active infection is present.
  • B-PLL or Richter transformation is diagnosed or suspected (e.g. symptoms or cytology).
  • There is involvement of the central nervous system.
  • The patient is known to be positive for human immunodeficiency virus (HIV).
  • CMV viremia is present, as demonstrated by pp65 EA or CMV-DNA.
  • The patient has previously been treated with alemtuzumab. (Exception: alemtuzumab used in a "non-therapeutic" context, i.e. administered as part of a conditioning regimen prior to SCT).
  • The patient has received autologous or allogeneic SCT within the past six months.
  • The patient is receiving long-term systemic treatment with corticosteroids or has received such treatment in the four weeks before first treatment with alemtuzumab.
  • Any additional active malignancy is present.
  • The patient has ever had an anaphylactic response to humanized antibodies.
  • For female patients: The patient is pregnant or lactating.
  • The patient has a history of drug or alcohol abuse that might lead to inability to comply with the protocol.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (38)

Hanuschkrankenhaus Wien

Vienna, Austria

Location

University Hospital

Vienna, Austria

Location

Centre Hospitalier de la Côte Basque

Bayonne, France

Location

Hopital Avicenne

Bobigny, 93009, France

Location

CHU Estaing

Clermont-Ferrand, France

Location

Hôpital Henri Mondor, Creteil -APHP

Créteil, France

Location

CHU de Grenoble

Grenoble, France

Location

CHU Claude Huriez

Lille, France

Location

Hôpital Edouard Herriot Lyon

Lyon, France

Location

CHU de Nancy

Nancy, France

Location

CHU Nantes

Nantes, France

Location

Hôpital Pitié Salpêtrière Paris-APHP

Paris, France

Location

Hôpital Saint-Louis Paris -APHP

Paris, France

Location

Centre Hospitalier Marechal Joffre Hôpital Saint-Jean Perpignan

Perpignan, France

Location

CHU de Poitiers

Poitiers, France

Location

CHU Robert-Debre

Reims, 51092, France

Location

CHU de Tours

Tours, France

Location

Charité CBF Berlin

Berlin, Germany

Location

University of Cologne

Cologne, Germany

Location

Dresden Universtiy Hospital

Dresden, Germany

Location

Essen University

Essen, Germany

Location

Freiburg University

Freiburg im Breisgau, Germany

Location

Goettingen University

Göttingen, Germany

Location

LMU Munich

Großhadern, Germany

Location

AK St. Georg Hamburg

Hamburg, Germany

Location

Hannover medical school (MHH)

Hanover, Germany

Location

Heidelberg University

Heidelberg, Germany

Location

Homburg/Saar University

Homburg/Saar, Germany

Location

Dr. Soeling Kassel

Kassel, Germany

Location

Kiel University

Kiel, Germany

Location

Mainz University

Mainz, Germany

Location

TU Munich

Munich, Germany

Location

Nuernberg University Hospital

Nuremberg, Germany

Location

OncoProGbR Regensburg

Regensburg, Germany

Location

Universtiy of Tuebingen

Tübingen, Germany

Location

University of ulm

Ulm, 89081, Germany

Location

Dr. Schlag Wuerzburg

Würzburg, Germany

Location

University Hospital Wuerzburg

Würzburg, Germany

Location

Related Publications (2)

  • Edelmann J, Holzmann K, Tausch E, Saunderson EA, Jebaraj BMC, Steinbrecher D, Dolnik A, Blatte TJ, Landau DA, Saub J, Estenfelder S, Ibach S, Cymbalista F, Leblond V, Delmer A, Bahlo J, Robrecht S, Fischer K, Goede V, Bullinger L, Wu CJ, Mertens D, Ficz G, Gribben JG, Hallek M, Dohner H, Stilgenbauer S. Genomic alterations in high-risk chronic lymphocytic leukemia frequently affect cell cycle key regulators and NOTCH1-regulated transcription. Haematologica. 2020 May;105(5):1379-1390. doi: 10.3324/haematol.2019.217307. Epub 2019 Aug 29.

    PMID: 31467127DERIVED

  • Steinbrecher D, Jebaraj BMC, Schneider C, Edelmann J, Cymbalista F, Leblond V, Delmer A, Ibach S, Tausch E, Scheffold A, Bloehdorn J, Hallek M, Dreger P, Dohner H, Stilgenbauer S. Telomere length in poor-risk chronic lymphocytic leukemia: associations with disease characteristics and outcome. Leuk Lymphoma. 2018 Jul;59(7):1614-1623. doi: 10.1080/10428194.2017.1390236. Epub 2017 Oct 24.

    PMID: 29063805DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-CellChromosome 17 deletion

Interventions

Alemtuzumab

Condition Hierarchy (Ancestors)

Leukemia, B-CellLeukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Stephan Stilgenbauer, Prof Dr med

    University of Ulm

    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
PRINCIPAL INVESTIGATOR
PI Title
Prof. Dr. med.

Study Record Dates

First Submitted

June 28, 2011

First Posted

July 12, 2011

Study Start

February 1, 2008

Primary Completion

January 1, 2012

Study Completion

March 1, 2016

Last Updated

October 24, 2019

Record last verified: 2019-10

Locations

FR(15)DE(21)AU(2)