T-cell-prolymphocytic LeukemiaPhase 2NCT01186640
Combined Immunochemotherapy in Patients With T-Prolymphocytic Leukemia (T-PLL)
A Phase 2 study testing Fludarabine, Mitoxantrone, Cyclophosphamide and Alemtuzumab and Alemtuzumab in people with T-cell-prolymphocytic Leukemia, run by German CLL Study Group at 1 site in Germany.
Trial summary
Study hypothesis: Simultaneous FMC-Alemtuzumab administration followed by Alemtuzumab maintenance therapy in patients with T-PLL is feasible, safe and efficient. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- T-cell-prolymphocytic Leukemia
- What is being tested?
- Fludarabine, Mitoxantrone, Cyclophosphamide and Alemtuzumab and Alemtuzumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteGermany
- Study dates
- Jun 2010to May 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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
- Being tested
- Fludarabine, Mitoxantrone, Cyclophosphamide and Alemtuzumab, Alemtuzumab
- Keywords
- T-PLL, Polychemotherapy, Alemtuzumab, Efficacy
- Medical subject headings
- Leukemia, Prolymphocytic, T-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fludarabine, Mitoxantrone, Cyclophosphamide and AlemtuzumabDrug
Also called Mabcampath, Fludarabine, Endoxan, Novantron
- 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.
AlemtuzumabDrug
Also called Mabcampath
maintenance with Alemtuzumab following a induction with combined immunochemotherapy consisting of Fludarabine, cyclophosphamide, mitoxantrone and alemtuzumab
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Fludarabine, Mitoxantrone, Cyclophosphamide and Alemtuzumab; Drug: Alemtuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 years after trial started
Secondary outcomes (1)
Overall Survival Time
OS will be calculated from the patient´s time of recruitment to death from any cause.
Measured: 4 years after start of trial
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2010 (estimated)
- Study startJun 2010
- Primary completionMay 2014
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for T-cell-prolymphocytic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- German CLL Study Group
- Sponsor type
- University, hospital or other
- Collaborators
- Genzyme, a Sanofi Company, University of Cologne
- Responsible party
- Sponsor
- Investigators
- Michael Hallek, Prof. MD, Principal investigator, German CLL Study Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01186640
- Sponsor's protocol ID
- T-PLL2
- Other IDs
- 2008-001421-34, 2008
- Status last verified
- May 2018
- First submitted
- 20 Aug 2010
- Last updated
- 5 Jan 2022
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 30234404
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Combined Immunochemotherapy With Fludarabine, Mitoxantrone, Cyclophosphamide and Alemtuzumab (FMC-Alemtuzumab) in Patients With Previously Treated or Untreated T-Prolymphocytic Leukemia
- ClinicalTrials.gov ID
- NCT01186640
- Acronym / sponsor ID
- T-PLL2
- Conditions
- T-cell-prolymphocytic Leukemia
- Keywords
- T-PLL, Polychemotherapy, Alemtuzumab, Efficacy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- German CLL Study GroupUniversity, hospital or other
- Collaborators
- Genzyme, a Sanofi Company, University of Cologne
- Study start
- Jun 2010
- Primary completion
- May 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 23 Aug 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| FCM-A followed by A-maintenance | Experimental | Drug: Fludarabine, Mitoxantrone, Cyclophosphamide and Alemtuzumab, Drug: AlemtuzumabFirst treatment phase: Chemoimmunotherapy A-FMC maximum 4 cycles. Second treatment phase: Maintenance-treatment with 30mg Alemtuzumab s.c. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fludarabine, Mitoxantrone, Cyclophosphamide and AlemtuzumabAlso: Mabcampath, Fludarabine, Endoxan, NovantronI. 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. | Drug | FCM-A followed by A-maintenance |
| AlemtuzumabAlso: Mabcampathmaintenance with Alemtuzumab following a induction with combined immunochemotherapy consisting of Fludarabine, cyclophosphamide, mitoxantrone and alemtuzumab | Drug | FCM-A followed by A-maintenance |
Primary outcome
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.
1 secondary outcome
Overall Survival Time
Time frame: 4 years after start of trial
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2022.
- Results publication: PubMed 30234404Pflug 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Hallek, Prof. MD principal investigator
German CLL Study Group
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fludarabine, Mitoxantrone, Cyclophosphamide and Alemtuzumab and Alemtuzumab in people with T-cell-prolymphocytic Leukemia, run by German CLL Study Group at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Remission Rate (time frame: 2 years after trial started). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01186640, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2022.