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

NCT01186640 | Completed Phase 2

• 2 other identifiers: T-PLL22008-001421-34
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

T-cell-prolymphocytic Leukemia

Keywords

T-PLL; Polychemotherapy; Alemtuzumab; Efficacy

Outcome Measures

Primary Outcomes (1)

• Remission Rate

  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 Outcomes (1)

• Overall Survival Time

  4 years after start of trial

Study Arms (1)

FCM-A followed by A-maintenance

EXPERIMENTAL

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

Interventions

Fludarabine, Mitoxantrone, Cyclophosphamide and Alemtuzumab 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.

Also known as: Mabcampath, Fludarabine, Endoxan, Novantron

FCM-A followed by A-maintenance

Alemtuzumab DRUG

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

Also known as: Mabcampath

FCM-A followed by A-maintenance

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• German CLL Study Group: lead
• Genzyme, a Sanofi Company: collaborator
• University of Cologne: collaborator

Study Sites (1)

University Hospital Cologne

Cologne, 50924, Germany

Location

Related Publications (1)

• 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.

  PMID: 30234404 RESULT

MeSH Terms

Conditions

Leukemia, Prolymphocytic, T-Cell

Interventions

fludarabine; Mitoxantrone; Cyclophosphamide; Alemtuzumab

Condition Hierarchy (Ancestors)

Leukemia, Prolymphocytic; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Leukemia, T-Cell; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Michael Hallek, Prof. MD

  German CLL Study Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2010
• First Posted: August 23, 2010
• Study Start: June 1, 2010
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: January 5, 2022

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)