Clinical Trial Results:
Phase II Trial of Combined Immunochemotherapy with Fludarabine, Mitoxantrone, Cyclophosphamide and Alemtuzumab (FMC-Alemtuzumab) in Patients with Previously Treated or Untreated T-Prolymphocytic Leukemia
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Summary
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EudraCT number |
2008-001421-34 |
Trial protocol |
DE AT |
Global end of trial date |
29 May 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
13 Dec 2021
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First version publication date |
13 Dec 2021
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
TPLL2
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01186640 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
PEI: 962/01 | ||
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Sponsors
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Sponsor organisation name |
University of Cologne
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Sponsor organisation address |
Albertus-Magnus-Platz, Cologne, Germany, 50923
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Public contact |
Information Desk, German CLL Study Group, 0049 22147888220, cll-studie@uk-koeln.de
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Scientific contact |
Information Desk, German CLL Study Group, 0049 22147888220, cll-studie@uk-koeln.de
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
02 Oct 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
29 May 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
29 May 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The objective of the T-PLL2-study is to assess remission rate, number of serious adverse events, number of life-threatening infections of simultaneous FMC-Alemtuzumab administration followed by Alemtuzumab-maintenance therapy in patients with T-PLL.
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Protection of trial subjects |
I. Premedication
Patients should be treated with
- Antihistamine (e.g. Diphenhydramine/Tavegil® 2mg i.v.)
- Paracetamol/Acetaminophen (1000mg p.o.)
- Prednisolone (e.g. Solu-Decortin® 100mg i.v.)
30 minutes before the administration of Alemtuzumab during the first
cycle and on the first day of the subsequent cycles of A-FMC and
Alemtuzumab-maintenance treatment, plus in cases this premedication
is clinically indicated (e.g., when there are adverse effects due to an
infusion).
If a patient did not show any adverse effects, the premedication could
be omitted on day 2 and 3 of each cycle.
Any patient considered being at risk of an infusion related reaction
and/or tumour lysis syndrome (pts. with a lymphocytosis > 100,000/l)
should have received appropriate hydration, urine alkalisation with
intravenous bicarbonate and allopurinol before the beginning of
treatment and thereafter until the risk is ruled out.
II. Infection prevention
Patients should have received
- Trimethoprim / Sulfamethoxazole (e.g. two tablets Cotrim forte®
three times a week)
- Valgancyclovir (. 2x 450mg p.o./day)
or equivalent medications from the beginning until 4 months after the
end of the treatment.
Prophylactic antifungal medication, e.g., with 100 mg Fluco-nazole, and
use of growth factors like G-CSF and Erythropo-etin could be
administered according to institutional standards.
No live vaccines should have been administered during the treatment;
responses to inactivated, recombinant and cell wall-vaccines were
unreliable and suboptimal in these patients.
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Background therapy |
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 regi-men (FMC = Fludarabine, Mitoxantrone and Cyclophos-phamide) was tested, a preliminary analysis of 16 patients revealed a response rate of more than 60% after FMC-poly-chemotherapy and 83% after the subsequent administration of Alemtuzumab. The goal of the T-PLL2-protocol is to assess if the simulta-neous administration of FMC-polychemotherapy and -Alem-tuzumab with a subsequent Alemtuzumab-maintenance the-rapy is capable of improving the remission rate and the disease-free survival time in patients with T-PLL. | ||
Evidence for comparator |
n/a | ||
Actual start date of recruitment |
01 Jun 2010
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 18
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Worldwide total number of subjects |
18
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EEA total number of subjects |
18
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
7
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From 65 to 84 years |
11
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85 years and over |
0
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Recruitment
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Recruitment details |
It was planned to enroll 16 patients. In total 18 patients were enrolled between 06/2010 and 05/2014 | ||||||||||||||
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Pre-assignment
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Screening details |
20 T-PLL patients were registered for the trial. The central screening was performed by the GCLLSG central study office in Cologne, Germany and included immunophenotyping, anaylsis of TCL1 signaling and cytogenetic analysis. Of those 20 patients, 2 patient were assessed as screening failure, 18 patients were enrolled. | ||||||||||||||
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Pre-assignment period milestones
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Number of subjects started |
20 [1] | ||||||||||||||
Number of subjects completed |
18 | ||||||||||||||
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Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
Protocol deviation: 2 | ||||||||||||||
| Notes [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: All patients who meet the eligibility criteria for the study entry can be enrolled into the trial. To verify the eligibility of patients, a patient screening by a medical review of the pretherapeutic staging as well as a central immunophenotyping, analysis of the TCL1 signaling and the cytogenetics will be performed before randomization. 20 patients started pre-assignment period, 2 patient were assessed as screening failure, 18 patients were enrolled. |
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
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Arms
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Arm title
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FMC-Alemtuzumab | ||||||||||||||
Arm description |
All patients received a combination therapy of Fludarabine, Mitoxantrone, Cyclophosphamide and Alemtuzumab (A-FMC), followed by Alemtuzumab maintenance treatment. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Fludarabine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
First treatment phase Chemoimmunotherapy A-FMC: 20 mg/m2 i.v., days 1-3; Repeat day 29, maximum 4 cycles.
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Investigational medicinal product name |
Mitoxantrone
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Investigational medicinal product code |
09393
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
First treatment phase Chemoimmunotherapy A-FMC: 6 mg/m2 i.v., day 1; Repeat day 29, maximum 4 cycles.
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Investigational medicinal product name |
Cyclophosphamide
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Investigational medicinal product code |
1001995601
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
First treatment phase Chemoimmunotherapy A-FMC: 200 mg/m2 i.v., days 1-3; Repeat day 29, maximum 4 cycles.
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Investigational medicinal product name |
Alemtuzumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
First treatment phase Chemoimmunotherapy A-FMC
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
Second treatment phase Maintenance-treatment with 30mg Alemtuzumab s.c. for patients in CR, PR or SD; The maintenance therapy started one month after the Final Staging
and was administered monthly during the first six months plus once in
month 10 and 13.
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
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End points reporting groups
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Reporting group title |
FMC-Alemtuzumab
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Reporting group description |
All patients received a combination therapy of Fludarabine, Mitoxantrone, Cyclophosphamide and Alemtuzumab (A-FMC), followed by Alemtuzumab maintenance treatment. | ||
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End point title |
Overall response rate [1] | ||||||||
End point description |
Remission rate (ocurence of CRs, CRis, nPRs and PRs)
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End point type |
Primary
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End point timeframe |
Overall response rate was analysed within the final analysis in 2014 (data cut-off was 03.09.2014) . This analysis was not repeated for the final clinical study.
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: As the hypothesis states that the efficacy of the TPLL2 regimen is assessed uninteresting if the ORR rate is less than 50% and is confirmed if the ORR is at least 50% and as there are no further comparisons between different treatment arms, a frequency tabulation with no further statistical analyses was sufficient. So there are no statistical values available to provide. |
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Timeframe for AE
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Adverse event reporting additional description |
AE additional description
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.0
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Reporting groups
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Reporting group title |
FMC-A
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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01 Jul 2010 |
Amendment 1:
- Change of the start of the trial
- Reduction of the Alemtuzumab dosing and change in the treatment intervals
- Changes in the recomennded CMV prophylaxis
- Simplification of the Retreatment criteria and dose modification
- Correction of the registration and screening process
- Changes in the logisitic procedures of Alemtuzumab
- Changes for the immunophenotypig samples
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/30234404 |
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