Subcutaneous Alemtuzumab Combined With Oral Dexamethasone, Followed by Alemtuzumab Maintenance or Allo-SCT in CLL With 17p- or Refractory to Fludarabine

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2012 by University of Ulm.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
IMSE, TU Munich (Biometry)
WiSP GmbH, Langenfeld (Monitoring and Data Management)
Central study office of the GCLLSG Cologne
Information provided by (Responsible Party):
Stephan Stilgenbauer, University of Ulm
ClinicalTrials.gov Identifier:
NCT01392079
First received: June 28, 2011
Last updated: August 30, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Chronic Lymphocytic Leukemia
Drug: Alemtuzumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective, Multi-center Phase II Study of Subcutaneous Alemtuzumab Combined With Oral Dexamethasone, Followed by Alemtuzumab Maintenance or Allogeneic Stem-cell Transplantation, in Chronic Lymphocytic Leukemia Which is Associated With 17p Deletion or is Refractory to Fludarabine

Resource links provided by NLM:


Further study details as provided by University of Ulm:

Primary Outcome Measures:
  • Response rate [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]

    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.


Secondary Outcome Measures:
  • Progression-free-survival [ Time Frame: up to five years ] [ Designated as safety issue: No ]
    Progression-free survival: time from study entry to the detection of progressive disease according to NCI criteria or death of any cause, whichever occurs first.

  • Failure-free survival [ Time Frame: up to five years ] [ Designated as safety issue: No ]
    Failure-free survival: time from study entry until next treatment, detection of progressive disease according to NCI criteria or death of any cause, whichever occurs first.

  • Overall survival [ Time Frame: up to five years ] [ Designated as safety issue: No ]
    Time from study entry to death of any cause.

  • Number of participants with Adverse Events as a measure of safety and tolerability [ Time Frame: up to 2.5 years ] [ Designated as safety issue: Yes ]
    Acquisition of further data to expand the data base on the toxicity of the study treatment. (Type, frequency, severity, timing and relatedness of AEs and laboratory abnormalities observed during different treatment cycles)


Estimated Enrollment: 122
Study Start Date: February 2008
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Alemtuzumab

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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. The patient has CLL requiring treatment (Binet C or A/B with "active disease" according to the NCI criteria).
  2. 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)).
    • 17p deletion is present (irrespective of whether previously treated or untreated).
  3. The patient is at least 18 years of age.
  4. The patient's performance status is 0, 1 or 2 on the WHO/ECOG scale.
  5. Any previous chemotherapy and/or immunotherapy ended at least four weeks before the first study treatment with alemtuzumab.
  6. The patient has recovered from all previous chemotherapy and/or immunotherapy.
  7. For fertile men and for women of childbearing potential: Adequate contraception (oral contraceptives, intrauterine device or barrier method in conjunction with spermicidal jelly).
  8. The patient has given written informed consent to participate in the study.

Exclusion Criteria:

  1. The patient has received more than five different prior therapeutic regimens.
  2. 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).
  3. 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.
  4. Any active infection is present.
  5. B-PLL or Richter transformation is diagnosed or suspected (e.g. symptoms or cytology).
  6. There is involvement of the central nervous system.
  7. The patient is known to be positive for human immunodeficiency virus (HIV).
  8. CMV viremia is present, as demonstrated by pp65 EA or CMV-DNA.
  9. 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).
  10. The patient has received autologous or allogeneic SCT within the past six months.
  11. The patient is receiving long-term systemic treatment with corticosteroids or has received such treatment in the four weeks before first treatment with alemtuzumab.
  12. Any additional active malignancy is present.
  13. The patient has ever had an anaphylactic response to humanized antibodies.
  14. For female patients: The patient is pregnant or lactating.
  15. The patient has a history of drug or alcohol abuse that might lead to inability to comply with the protocol.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01392079

Locations
Austria
University Hospital
Wien, Austria
Hanuschkrankenhaus Wien
Wien, Austria
France
Centre Hospitalier de la Côte Basque
Bayonne, France
Hopital Avicenne
Bobigny Cedex, France, 93009
CHU Estaing
Clermont-Ferrand, France
Hôpital Henri Mondor, Creteil -APHP
CRETEIL Cedex, France
CHU de Grenoble
Grenoble, France
CHU Claude Huriez
Lille, France
Hôpital Edouard Herriot Lyon
Lyon, France
CHU de Nancy
NANCY Cedex, France
CHU Nantes
Nantes, France
Hôpital Pitié Salpêtrière Paris-APHP
Paris, France
Hôpital Saint-Louis Paris -APHP
Paris, France
Centre Hospitalier Marechal Joffre Hôpital Saint-Jean Perpignan
PERPIGNAN Cedex, France
CHU de Poitiers
POITIERS Cedex, France
CHU Robert-Debre
Reims, France, 51092
CHU de Tours
Tours, France
Germany
Charité CBF Berlin
Berlin, Germany
University of Cologne
Cologne, Germany
Dresden Universtiy Hospital
Dresden, Germany
Essen University
Essen, Germany
Freiburg University
Freiburg, Germany
Goettingen University
Goettingen, Germany
LMU Munich
Grosshadern, Germany
AK St. Georg Hamburg
Hamburg, Germany
Hannover medical school (MHH)
Hannover, Germany
Heidelberg University
Heidelberg, Germany
Homburg/Saar University
Homburg/Saar, Germany
Dr. Soeling Kassel
Kassel, Germany
Kiel University
Kiel, Germany
Mainz University
Mainz, Germany
TU Munich
Munich, Germany
Nuernberg University Hospital
Nuernberg, Germany
OncoProGbR Regensburg
Regensburg, Germany
Universtiy of Tuebingen
Tuebingen, Germany
University of ulm
Ulm, Germany, 89081
University Hospital Wuerzburg
Wuerzburg, Germany
Dr. Schlag Wuerzburg
Wuerzburg, Germany
Sponsors and Collaborators
University of Ulm
IMSE, TU Munich (Biometry)
WiSP GmbH, Langenfeld (Monitoring and Data Management)
Central study office of the GCLLSG Cologne
Investigators
Principal Investigator: Stephan Stilgenbauer, Prof Dr med University of Ulm
  More Information

No publications provided

Responsible Party: Stephan Stilgenbauer, Prof. Dr. med., University of Ulm
ClinicalTrials.gov Identifier: NCT01392079     History of Changes
Other Study ID Numbers: Cll2O, 2007-003099-20
Study First Received: June 28, 2011
Last Updated: August 30, 2012
Health Authority: Germany: Paul-Ehrlich-Institut
Austria: Agency for Health and Food Safety
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University of Ulm:
CLL
17p deletion
refractory to fludarabine
subcutaneous alemtuzumab
CLL with 17p- or refractory to fludarabine

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Alemtuzumab
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Fludarabine
Fludarabine phosphate
Anti-Inflammatory Agents
Antiemetics
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on October 22, 2014