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Phase II Trial of Combined Immunochemotherapy With Fludarabine, Mitoxantrone, Cyclophosphamide and Alemtuzumab (FMC-Alemtuzumab) in Patients With Previously Treated or Untreated T-Prolymphocytic Leukemia

Phase 2
18 Years
Open (Enrolling)
T-cell-prolymphocytic Leukemia

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Trial Information

Phase II Trial of Combined Immunochemotherapy With Fludarabine, Mitoxantrone, Cyclophosphamide and Alemtuzumab (FMC-Alemtuzumab) in Patients With Previously Treated or Untreated T-Prolymphocytic Leukemia

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

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

- 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

- Patients who are employees of the Sponsor (University of Cologne) or the study

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Remission Rate

Outcome Description:

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.

Outcome Time Frame:

2 years after trial started

Safety Issue:



Germany: Paul-Ehrlich-Institut

Study ID:




Start Date:

December 2009

Completion Date:

December 2015

Related Keywords:

  • T-cell-prolymphocytic Leukemia
  • T-PLL
  • Polychemotherapy
  • Alemtuzumab
  • Efficacy
  • Leukemia
  • Leukemia, Prolymphocytic
  • Leukemia, Prolymphocytic, T-Cell