Combined Immunochemotherapy in Patients With T-Prolymphocytic Leukemia (T-PLL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01186640
Recruitment Status : Completed
First Posted : August 23, 2010
Last Update Posted : September 26, 2016
Genzyme, a Sanofi Company
University of Cologne
Information provided by (Responsible Party):
German CLL Study Group

August 20, 2010
August 23, 2010
September 26, 2016
June 2010
May 2014   (Final data collection date for primary outcome measure)
Remission Rate [ Time Frame: 2 years after trial started ]
Efficacy of the FMC therapy and Alemtuzumab Percentage and 95%-confidence-interval of response rates (CR, CRi, nPR, PR, SD and PD) will be provided.
Same as current
Complete list of historical versions of study NCT01186640 on Archive Site
Overall Survival Time [ Time Frame: 4 years after start of trial ]
OS will be calculated from the patient´s time of recruitment to death from any cause.
Same as current
Not Provided
Not Provided
Combined Immunochemotherapy in Patients With T-Prolymphocytic Leukemia (T-PLL)
Phase II Trial of Combined Immunochemotherapy With Fludarabine, Mitoxantrone, Cyclophosphamide and Alemtuzumab (FMC-Alemtuzumab) in Patients With Previously Treated or Untreated T-Prolymphocytic Leukemia
Study hypothesis: Simultaneous FMC-Alemtuzumab administration followed by Alemtuzumab maintenance therapy in patients with T-PLL is feasible, safe and efficient.

As the median survival time of patients with T-PLL is less than 12 months, the treatment of T-PLL is a special challenge.

The overall response rates with conventional chemotherapy or Deoxycoformycin were low (about 30% and 40%), with the monoclonal antibody Alemtuzumab response rates of 50% to 70% were achieved, but the duration of the response was short.

In the previous trial (T PLL 1), the efficacy of the FMC regimen (FMC = Fludarabine, Mitoxantrone and Cyclophosphamide) was tested, a preliminary analysis of 16 patients revealed a response rate of more than 60% after FMC-polychemotherapy and 83% after the subsequent administration of Alemtuzumab.

The goal of the T-PLL2-protocol is to assess if the simultaneous administration of FMC-polychemotherapy and Alemtuzumab with a subsequent Alemtuzumab maintenance therapy is capable of improving the remission rate and the disease-free survival time in patients with T-PLL.

Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
T-cell-prolymphocytic Leukemia
  • Drug: Fludarabine, Mitoxantrone, Cyclophosphamide and Alemtuzumab

    I. First treatment phase: Chemoimmunotherapy A-FMC


    Cycle 1+2:

    10 mg s.c., days 1-3

    Cycle 3+4:

    CR: 10 mg s.c., days 1-3 PR/SD: 30 mg s.c., days 1-3 Fludarabine: 20 mg/m2 i.v., days 1-3 Mitoxantrone: 6 mg/m2 i.v., day 1 Cyclophosphamide: 200 mg/m2 i.v., days 1-3 Repeat day 29, maximum 4 cycles. II. Second treatment phase: Maintenance-treatment with 30mg Alemtuzumab s.c. The maintenance therapy will start one month after the Final Staging and will be administered monthly during the first six months plus once in month 10 and 13.

    Other Names:
    • Mabcampath
    • Fludarabine
    • Endoxan
    • Novantron
  • Drug: Alemtuzumab
    maintenance with Alemtuzumab following a induction with combined immunochemotherapy consisting of Fludarabine, cyclophosphamide, mitoxantrone and alemtuzumab
    Other Name: Mabcampath
Experimental: FCM-A followed by A-maintenance
First treatment phase: Chemoimmunotherapy A-FMC maximum 4 cycles. Second treatment phase: Maintenance-treatment with 30mg Alemtuzumab s.c.
  • Drug: Fludarabine, Mitoxantrone, Cyclophosphamide and Alemtuzumab
  • Drug: Alemtuzumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Same as current
May 2014
May 2014   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Untreated patients with T-prolymphocytic leukemia (T-PLL) according to WHO criteria or pretreated patients (max. one previous treatment) with T-PLL
  • Age ≥ 18 years
  • WHO performance status of 0-2
  • Life expectancy > 6 months
  • CIRS score >= 6
  • Left ventricular ejection fraction ≥50% confirmed by echo-cardiogram performed < 6 months before inclusion to the trial and after the end of a possible anthracycline containing pretreatment
  • Adequate liver function as indicated by a total bilirubin, AST and ALT >= 2 the institutional ULN value, unless directly attributable to the T-PLL
  • Creatinine clearance >= 70 ml/min calculated according to the formula of Cockcroft and Gault
  • Seronegativity for HIV, HBV or HCV confirmed by serological testing within 6 weeks prior to registration
  • Willingness of fertile male and female patients to use a highly effective contraceptive method with a Pearl-Index < 1 during and at least six months after the end of the study treatment (e.g. implants, injectables, oral contraceptives in combination with another contraceptive method, some IUDs, sexual abstinence or vasectomised partner)
  • Negative serum pregnancy test one week prior to treatment (required for female patients before and <2 years after onset of menopause)
  • Patient's written informed consent

Exclusion Criteria:

  • Clinically significant auto-immune cytopenia or clinically significant hemolytic anaemia with suspicion of immune origin, even if Coombs test is negative
  • Active secondary malignancy requiring treatment (except basal cell carcinoma or tumour curatively treated by surgery)
  • Medical condition requiring prolonged use of oral corticosteroids (> 1 month)
  • Cerebral dysfunction, legal incapacity
  • Any circumstance at the time of study entry that would preclude completion of the study and required follow-up
  • Active infection or severe infection (WHO 4th degree) within the last three months before inclusion to the study
  • Participation in any other clinical trial during this study
  • Known hypersensitivity to any of the study medications (Fludarabine, Cyclophosphamide, Mitoxantrone or Alemtuzumab)
  • Patients who have already received more than 60% of the recommended maximum cumulative dose of an anthracycline (Epirubicine, Adriamycine or Mitoxantrone).

This maximum cumulative dose is defined for the individual substances as follows:

  • Epirubicin 900 mg/m²
  • Daunorubicin 550 mg/m², (or 400 mg/m² if the patient received mediastinal irradiation)
  • Adriamycine (Doxorubicine) 550 mg/m²
  • Mitoxantrone 200 mg/m²

    • Patients who already received Fludarabine in combination with Cyclophosphamide or Mitoxantrone
    • Patients who received prior treatment with Alemtuzumab alone or in combination with a purine analogue and who did not achieve a PR that lasted at least 6 months
    • Patients who are employees of the Sponsor (University of Cologne) or the study sites.
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
2008-001421-34 ( EudraCT Number )
Not Provided
Plan to Share IPD: No
German CLL Study Group
German CLL Study Group
  • Genzyme, a Sanofi Company
  • University of Cologne
Principal Investigator: Michael Hallek, Prof. MD German CLL Study Group
German CLL Study Group
September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP