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

December 16, 2021 updated by: German CLL Study Group

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

16

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Cologne, Germany, 50924
        • University Hospital Cologne

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

I. First treatment phase: Chemoimmunotherapy A-FMC

Alemtuzumab:

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:
  • Endoxan
  • Fludarabine
  • Novantron
  • Mabcampath
Drug: Alemtuzumab
maintenance with Alemtuzumab following a induction with combined immunochemotherapy consisting of Fludarabine, cyclophosphamide, mitoxantrone and alemtuzumab
Other Names:
  • Mabcampath

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
2 years after trial started

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
4 years after start of trial

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

German CLL Study Group

Collaborators

Genzyme, a Sanofi Company
University of Cologne

Investigators

  • Principal Investigator: Michael Hallek, Prof. MD, German CLL Study Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2010

Primary Completion (Actual)

May 1, 2014

Study Completion (Actual)

May 1, 2014

Study Registration Dates

First Submitted

August 20, 2010

First Submitted That Met QC Criteria

August 20, 2010

First Posted (Estimate)

August 23, 2010

Study Record Updates

Last Update Posted (Actual)

January 5, 2022

Last Update Submitted That Met QC Criteria

December 16, 2021

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • T-PLL2
  • 2008-001421-34 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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