Clinical Trial Results:
Obinutuzumab containing conditioning regimen for CLL patients and patients with Richter`s transformation requiring an allogeneic stem cell transplantation
Summary
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EudraCT number |
2015-000568-32 |
Trial protocol |
DE |
Global end of trial date |
30 Sep 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
07 Oct 2020
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First version publication date |
07 Oct 2020
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Other versions |
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 |
CLLTX1
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03153514 | ||
WHO universal trial number (UTN) |
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Other trial identifiers |
Paul-Ehrlich-Institut: 2918/01 | ||
Sponsors
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Sponsor organisation name |
German CLL Study Group, University Hospital Cologne
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Sponsor organisation address |
Gleuelerstr. 176-178, Cologne, Germany, 50935
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Public contact |
CLLTX1 , German CLL Study Group, 0049 0221478 88220, cllstudie@uk-koeln.de
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Scientific contact |
CLLTX1 , German CLL Study Group, 0049 0221478 88220, cllstudie@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 |
07 Aug 2020
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Sep 2019
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The primary objective of the study is to evaluate the feasibility, efficacy and safety of an Obinutuzumab containing conditioning regimen for CLL patients and patients with Richter`s transformation requiring an allogeneic stem cell transplantation.
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Protection of trial subjects |
A premedication with oral acetaminophen/paracetamol (1.000mg) and antihistamines including a H1- (e.g. dimentindene 4mg i.v.) and a H2-antagonist (e.g. ranitidine 50mg i.v.) has to be administered (unless contraindicated) approximately 30 minutes prior to the start of the first infusion of obinutuzumab to avoid infusion related reactions (IRRs). Additionally, prednisolone or prednisone (100mg given i.v. at least one hour before the obinutuzumab infusion) has to be administered. An equivalent dose of dexamethasone (16mg) or methylprednisolone (80mg) is permitted, but hydrocortisone should not be used.
In Addition detailed guidance on the Management on graft versus host disease were provided in the study protocol
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Background therapy |
The number of patients who received allogeneic stem cell transplantion has substantially decreased over time; mostly due to the availability of less toxic and novel agents with proven efficacy even after failure to chemoimmunotherapy or to chemofree first-line regimen. However, allogeneic stem cell transplantation continue to have a role for patients who fail, are intolerant, or do not have access to these novel agents Instead of Obinutuzumab, which was explored in this trial to collect data on the influence of obinutuzumab on the development of graft versus host disease, Antithymocyte globulin is used as graft versus host disease (GvHD) prophylaxis in most unrelated donor transplants. Another alternative is the use of Alemtuzumab in addition to calcineurin inhibitors and mycophenolate mofetil. The use of these T-cell depleting agents are associated with an increase rate of relapse. The protective role of Rituximab in the peri-transplant conditioning as well as its role in the treatment of GvHD highlights the potential for a B-cell depleting agent in the peri-transplant setting. Allo-SCT is not only a therapeutic option for patients with poor risk CLL and RT but also offers the possibility of potential cure. As myeloblative conditioning regimens are associated with a high transplant related morbidity and mortality (up to 40%) 8, reduced intensity conditioning regimens are currently preferred for these patients. Graft versus leukaemia (GvL) effect has been demonstrated post allo-SCT by many factors such as reduced relapse in the presence of chronic Graft versus host disease (GvHD), ability to eradicate minimal residual disease with the taper of immunsuppression or donor lymphocyte infusions (DLI) and increased relapse following T-cell depletion Encouragingly a recent follow-up by Dreger et al. on the CLL3X trial highlighted that the long term (6 years post SCT) survival on 90 allografted patients as 58% with an event free survival (EFS) of 38%. They also conclu | ||
Evidence for comparator |
n/a | ||
Actual start date of recruitment |
06 Apr 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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: 3
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Worldwide total number of subjects |
3
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EEA total number of subjects |
3
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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) |
2
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From 65 to 84 years |
1
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85 years and over |
0
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Recruitment
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Recruitment details |
3 patients were enrolled between 11/2017 and 04/2018. | ||||||
Pre-assignment
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Screening details |
4 pre-treated patients with high risk CLL or Richters transformation were registered for central screening. The central screening was performed by the GCLLSG study office in Cologne Germany and included immunophenotyping, transplant requirement, suitable stem cell donor, comorbidity and renal function. 1 patient was not eligible for participation. | ||||||
Pre-assignment period milestones
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Number of subjects started |
3 | ||||||
Number of subjects completed |
3 | ||||||
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 | ||||||
Blinding implementation details |
n/a
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Arms
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Arm title
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Obinutuzumab | ||||||
Arm description |
Patients received cycle 1 at the time of the stem cell transplantation. Cycle 2 was administered in case of active disease and/or MRD positivity after cycle 1. Patients were staged at day +60 post-transplant and MRD was determined per central laboratory assessment. Patients found to have active disease or identified as MRD positive, defined as those who have a MRD ≥ 10-4, were offered 4 additional doses of obinutuzumab along with immunetaper ± DLI. Patients who did not receive cycle 2 because staging at day +60 post-transplant showed no active disease and/or MRD positivity received cycle 2 after staging day +90/ 180/ 270 post-transplant if found to have active disease/MRD positivity at this time point. | ||||||
Arm type |
single-arm | ||||||
Investigational medicinal product name |
Obinutuzumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for concentrate for solution for infusion
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Routes of administration |
Intravenous drip use
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Dosage and administration details |
Obinutuzumab will be administered as depicted in Table 2 of the protocol. Regarding the administration of a premedication before the start of obinutuzumab, for adjustments in case of an IRR as well as further guidelines regarding obinutuzumab administration please refer to chapter 5.2.2 Premedication before obinutuzumab therapy and chapter 5.2.3 Infusion-related reactions and anaphylaxis. For obinutuzumab storage and preparation please refer to chaper 8.5 Drug storage and preparation. If the first infusion of obinutuzumab was well tolerated (defined by an absence of IRRs during a final infusion rate of ≥ 100mg/h), subsequent infusions will be administered at an initial rate of 100mg/h.
The infusion rate is increased by 100mg/h increments at 30 minute intervals, as tolerated, to a maximum rate of 400mg/h. At the investigator’s discretion the subsequent obinutuzumab infusions may be split and administered over two days with infusion rates as described in the protocol
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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 |
Obinutuzumab
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Reporting group description |
Patients received cycle 1 at the time of the stem cell transplantation. Cycle 2 was administered in case of active disease and/or MRD positivity after cycle 1. Patients were staged at day +60 post-transplant and MRD was determined per central laboratory assessment. Patients found to have active disease or identified as MRD positive, defined as those who have a MRD ≥ 10-4, were offered 4 additional doses of obinutuzumab along with immunetaper ± DLI. Patients who did not receive cycle 2 because staging at day +60 post-transplant showed no active disease and/or MRD positivity received cycle 2 after staging day +90/ 180/ 270 post-transplant if found to have active disease/MRD positivity at this time point. |
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End point title |
Rate of patients free from disease progression (PD-free rate) at 12 months post-transplant [1] | ||||||
End point description |
Patients will be followed for Progression. Patients free of disease Progression will be counted .
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End point type |
Primary
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End point timeframe |
12 months post transplant
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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: Because of the low number of patients no statistical analyses were done. |
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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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 |
CLLTX1
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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? No | |||
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. | |||
In this study, the recruitment was stopped after 3 of the 40 planned patients have been enrolled. As a consequence of the low number of of patients enrolled, it was decided that any statistical analysis cannot be performed. |