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

Phase 2

Completed

• Conditions: T-cell-prolymphocytic Leukemia
• Interventions: Drug: Fludarabine, Mitoxantrone, Cyclophosphamide and Alemtuzumab; Drug: Alemtuzumab

• Registration Number: NCT01186640
• Lead Sponsor: German CLL Study Group

Brief Summary

Study hypothesis: Simultaneous FMC-Alemtuzumab administration followed by Alemtuzumab maintenance therapy in patients with T-PLL is feasible, safe and efficient.

Detailed Description

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.

Study Timeline

• Study Start: 2010-06
• Study First Submitted: 2010-08-20
• Study First Submitted QC: 2010-08-20
• Study First Posted: 2010-08-23
• Primary Completion: 2014-05
• Study Completion: 2014-05
• Status Verified: 2018-05
• Last Update Submitted: 2021-12-16
• Last Update Posted: 2022-01-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
FCM-A followed by A-maintenance	Fludarabine, Mitoxantrone, Cyclophosphamide and Alemtuzumab	First treatment phase: Chemoimmunotherapy A-FMC maximum 4 cycles. Second treatment phase: Maintenance-treatment with 30mg Alemtuzumab s.c.
FCM-A followed by A-maintenance	Alemtuzumab	First treatment phase: Chemoimmunotherapy A-FMC maximum 4 cycles. Second treatment phase: Maintenance-treatment with 30mg Alemtuzumab s.c.

Primary Outcome Measures

Name	Time	Method
Remission Rate	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival Time	4 years after start of trial	OS will be calculated from the patient´s time of recruitment to death from any cause.

Trial Locations

Locations (1)

University Hospital Cologne; 🇩🇪 Cologne, Germany