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

NCT ID: NCT01186640

Last Updated: 2022-01-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30
• Study Completion Date: 2014-05-31

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.

Conditions

T-cell-prolymphocytic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Fludarabine, Mitoxantrone, Cyclophosphamide and Alemtuzumab

Intervention Type: DRUG

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.

Alemtuzumab

Intervention Type: DRUG

maintenance with Alemtuzumab following a induction with combined immunochemotherapy consisting of Fludarabine, cyclophosphamide, mitoxantrone and alemtuzumab

Interventions

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.

Intervention Type: DRUG

Alemtuzumab

maintenance with Alemtuzumab following a induction with combined immunochemotherapy consisting of Fludarabine, cyclophosphamide, mitoxantrone and alemtuzumab

Intervention Type: DRUG

Other Intervention Names

Mabcampath; Fludarabine; Endoxan; Novantron; Mabcampath

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: collaborator

University of Cologne

OTHER

Sponsor Role: collaborator

German CLL Study Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Hallek, Prof. MD

Role: PRINCIPAL_INVESTIGATOR

German CLL Study Group

Locations

University Hospital Cologne

Cologne, , Germany

Countries

Germany

References

Pflug N, Cramer P, Robrecht S, Bahlo J, Westermann A, Fink AM, Schrader A, Mayer P, Oberbeck S, Seiler T, Zenz T, Durig J, Kreuzer KA, Stilgenbauer S, Eichhorst B, Hallek M, Herling M, Hopfinger G. New lessons learned in T-PLL: results from a prospective phase-II trial with fludarabine-mitoxantrone-cyclophosphamide-alemtuzumab induction followed by alemtuzumab maintenance. Leuk Lymphoma. 2019 Mar;60(3):649-657. doi: 10.1080/10428194.2018.1488253. Epub 2018 Sep 20.

Reference Type: RESULT

PMID: 30234404 (View on PubMed)

Other Identifiers

2008-001421-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

T-PLL2

Identifier Type: -

Identifier Source: org_study_id