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Clinical picture: NHL (Non Hodgkin Lymphoma)

Trial: HOVON 119 MCL


News
1. Overview
2. Patient eligibility criteria
3. Registration (& randomization) of patients
4. Participating parties
5. Participating sites
6. Instruction videos
7. Download documentation / forms


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News


HO119 status

 

URL for IWRS: http://www.clininfohosting.com/specif/MCLR2_ELDERLY/

URL for eCRF: http://study.lysarc.info/ (choose MCL-R2-Elderly)

 

Updated documents:

  13-SEP-2017
• DSUR IV has been made available.
• IB rituximab SC v7 - addendum 1 has been made available.
• delegation log version v2.0 dd 22-may-2017 replaces the previous version.
• ABR formulier versie 07 dd 17-07-2017 replaces the previous version.
• The CCMO and METc approval documents are available for download.

 

   27-JAN-2017

• HO119 MCL R2 Elderly protocol v5.2 dd 08-09-2016 replaces the previous version HO119 MCL R2 Elderly protocol v5.1 dd 12-10-2015.
• DSUR III, Jaarlijkse veiligheidsrapportage MCL R2 ELDERLY dd 06-07-2017 has been made available.
• IB lenalidomide V20 (and in between V19) replaces previous version IB lenalidomide V18.

• IB rituximab SC V7 replaces the previous version IB Rituximab SC V6.
• Ho119 MCL Contact sheet v3.0 27-01-2017 replaced version 2.0 04-12-2015.
• The cumulative CCMO and METc approval documents have been updated accordingly.

    04-MAR-2016

• The HO119 monitoring and completion guidelines V4.0 28-OKT-2015 replaces the previous version MCL-R2 Elderly_Monitoring and completion guidelines_v2.0 20141017.

• The HO119 HOVON Subject Identification Log v2.0 16-FEB-2016 replaces the previous version 01 21-08-2013.

       08-DEC-2015 - amendment 01 implemented

• HO119 MCL R2 ELderly Protocol V5.1 d.d 12-10-2015 replaces previous version V4.0 d.d. 17-03-2014
• HO119 MCLR2 Elderly-protocol signature page_v5.1 NL replaces previous version 4.0

• HO119 lenalidomide education and counseling guidance document V4.0 19Dec2014 and patient information sheet V4.0 19Dec2014 replace the previous lenalidomide education and counseling guidance document v1_31mar2015 and patient information sheet v3_mei2010

• IB lenalidomide V18 replaces previous version IB lenalidomide V17

• IB rituximab SC V6 replaces the previous version IB Rituximab SC V5

• HO119 verpleegkundige samenvatting V.26.01.2015, protocol_5.1 Study flow chart.pdf replaces the previous ho119-verpleegkundige-samenvatting-study-flow.pdf

• HO119 METC Erasmus MC approval for amendment 01 d.d. 30NOV2015 & previous approval made available

• HO119 CCMO response amendment 01 26NOV2015 + previous approval made available

• HO119 HO119 MCL Contact sheet v2.0 04DEC15 replaces the previous version Ho119 MCL Contact sheet 26JAN15

     22-SEP-2015

• ho119 drug accountability forms rituximab sc and lenalidomide 05 10 15 mg.pdf made available

    26-AUG-2015

• Pathology review procedure 26-AUG-2015.pdf replaces the previous version 08 jun 2015.pdf

• MRD minimal residual disease memo and manuals 26-AUG-2015.pdf replaces the previous version 08 jun 2015.pdf

• IWRS userguide for investigators, trial coordinators v1.5.pdf 13-MAY-2015 replaces previous version v1.5 13-MAY-2015 (minor update)

    17-AUG-2015

• Removal from quarantine for Rituximab SC.pdf made available

• Alert form of temperature excursion_v2.0.pdf made available

• Management and administration of treatment units v1.0 01-AUG-2014.pdf made available

     02-JUL-2015:

• Financial disclosure form version 1.2 replaces the previous version 1.1

• IWRS userguide for investigators, trial coordinators v1.5.pdf made available

• IWRS userguide for Pharmacists v1.3.pdf made available

• Pathology review procedure v08 jun 2015.pdf made available

    28-MAY-2015:

• H119 ICF biologisch materiaal final versie 2.1 replaces the previous version 2.0

  

News

13-SEP-2017: Amendment 03 implemented

• documents approved: IB Rituximab SC v7 - addendum 1, DSUR IV

• New version of the delegation log implemented

• Changed investigators for centers UMCG-Groningen and Spaarne ziekenhuis-Hoofddorp

 

27-JUL-2017:

Usage of biosimilars of Rituximab Mabthera IV during HO119 MCL R2 Elderly induction treatment is approved. Please refer to the information letter "MCL-R2 Elderly_Jul 2017_use of biosimilar of Rituximab for induction tre....pdf", available for download in the "other documents" section below.

 

27-JAN-2017: Amendment 02 implemented

• New versions of documents approved: protocol, IB's  

• DSURIII available

 

08-DEC-2015: Amendment 01 implemented

• Participation of centers Zuyderland MC-Sittard-Geleen, OLVG-Amsterdam en Gemini ziekenhuis-den Helder approved

• Changed investigators for centers OLVG-Amsterdam, ADRZ-Goes and UMCG-Groningen.
• New versions of documents approved: protocol, IB's, Lenalidomide pregnancy prevention plan (among others).

 

29-JUL-2015:  First center opened for inclusion

26-MAY-2015: Sites provided with study documents

11-MAY-2015: METc approval obtained

  


1. Overview



Summary

Efficacy of alternating immunochemotherapy consisting of R-CHOP + RHAD versus R-CHOP alone, followed by maintenance therapy consisting of additional lenalidomide with rituximab versus rituximab alone for older patients with mantle cell lymphoma


Status

open


Members

Participating groups: FIL, LYSA, GLSG, HOVON, GELTAMO, PLRG and Portugese LSG.



Type of study

Prospective randomized Phase III study


Echelon level

Level D


Echelon level specification

limited to 25 sites


Type of monitoring for this study

Study specific


Target number of patients

633


Current number of patients

0


Date of activation

26-May-2015


Study objectives

The primary objective of the trial is to evaluate whether the addition of lenalidomide to rituximab-maintenance improves progression free survival (PFS) compared to standard rituximab maintenance after response to induction chemotherapy in older patients with mantle cell lymphoma not suitable for autologous stem cell transplantation.

The secondary efficacy objectives for the maintenance part are:
To compare the efficacy of maintenance therapy with rituximab plus lenalidomide versus rituximab alone following induction therapy using other parameters of efficacy:
• Time to event analyses
>>>overall survival from maintenance randomization and from induction randomization
>>>progression-free survival from induction randomization
• PR/CRu to CR and PR to CRu conversion during maintenance
• MRD status and levels in peripheral blood and bone marrow after one and two years from end of induction and during follow-up

The secondary safety objectives are:
• To compare the safety of maintenance therapy with rituximab plus lenalidomide versus rituximab alone following induction therapy using other parameters of efficacy:
>>>Toxicity (NCI CTCAE v 4.0)
>>>Adverse Events
>>>Second primary malignancies rates
• To assess potentially differential effects of maintenance according to induction (pre-defined subgroup analysis of maintenance effects according to induction)

The secondary efficacy objectives that will be analyzed according to induction therapy are:
• To evaluate whether the introduction of cytarabine into induction improves clinical outcome compared to standard R-CHOP in older patients with mantle cell lymphoma not suitable for autologous stem cell transplantation. This objective will be answered in a confirmatory way with overall survival from induction randomization as primary variable of interest. The previous study in this elderly population did show a significant difference in overall survival for the comparison of R-FC and R-CHOP, while no significant differences were observed for overall response rate, CR rate and time to treatment failure.
• To compare complete and overall response rates (based on Cheson 1999 criteria) at midterm and end of induction, time to treatment failure, and progression-free survival from induction randomization of R-CHOP / R-HAD versus R-CHOP alone
• To compare remission duration and OS from maintenance randomization of R-CHOP / R-HAD versus R-CHOP alone
• To compare MRD status and levels in peripheral blood and bone marrow at midterm and at the end of induction of R-CHOP / R-HAD versus R-CHOP alone

Exploratory objectives and endpoints
• To evaluate CR rate after induction / maintenance treatment by 2007 Revised Response Criteria for Malignant Lymphoma incorporating FDG-PET.
• To evaluate PR/CRu to CR and PR to CRu conversion during maintenance according to induction therapy.
• To evaluate MRD status and levels in peripheral blood and bone marrow after one and two years from end of induction and during follow-up according to induction therapy.


2. Patient eligibility criteria



Inclusion criteria

Patients must satisfy all the following criteria at study entry to be randomized in the trial:
1. Signed informed consent form
2. Biopsy-proven mantle cell lymphoma according to WHO classification, including evidence of cyclin D1 overexpression or the translocation t(11;14)(q13;q32).
3. ≥ 60 years of age and ineligible for autologous transplant
4. Ann Arbor stage II-IV
5. previously untreated (except for patients randomized directly for maintenance treatment who will receive 8 RCHOP before registration in the trial)
6. ECOG performance status ≤ 2
7. Male subjects must:
a. agree to use a condom during sexual contact with a woman of childbearing potential, even if they have had a vasectomy, throughout lenalidomide therapy
b. agree to not donate semen during lenalidomide therapy.
8. All subjects must:
a. have an understanding that the lenalidomide could have a potential teratogenic risk.
b. agree to abstain from donating blood while taking lenalidomide therapy
c. agree not to share study medication with another person.
d. be counseled about pregnancy precautions and risks of foetal exposure.

Additional criteria for randomization in maintenance phase:
CR, CRu or PR after induction treatment, determined as per Cheson 1999 criteria by investigator
During the run-in period of 6 months starting from the date of the first patient randomized in the trial: in case of direct randomization into maintenance phase, patient must have been treated in first line by 6-8 cycles of R-CHOP


Exclusion criteria

The presence of any of the following will exclude a subject from enrollment:
1. Female of child-bearing potential (i.e. without natural menopause for at least 24 consecutive months, a hysterectomy or bilateral oophorectomy)
2. Any of the following laboratory abnormalities at diagnosis, if not related to lymphoma:
a. Absolute neutrophils count <1,000 /mm^3 (1.0 x 10^9/L) if not result of a bone marrow infiltration.
b. Platelet count < 75,000/mm^3 (75 x 10^9/L) if not result of a bone marrow infiltration.
c. Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) >3.0 x upper limit of normal (ULN).
d. Serum total bilirubin > 1.5 ULN (except if due to Gilbert's syndrome)
3. Calculated creatinine clearance (Cockcroft-Gault formula or MDRD) < 30 mL /min.
4. Central Nervous System involvement by lymphoma
5. Contraindication for medical DVT prophylaxis for patients at high risk for DVT
6. Prior history of malignancies other than MCL unless the subject has been free of the disease for ≥ 5 years. Exceptions include the following:
a. Basal cell carcinoma of the skin,
b. Squamous cell carcinoma of the skin,
c. Carcinoma in situ of the cervix,
d. Carcinoma in situ of the breast,
e. Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b).
7. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient to receive the study medication as planned.
8. Poor cardiac function (LVEF < 50%) on echocardiography
9. Seropositivity for human immunodeficiency virus (HIV, mandatory test) at study entry
Seropositivity for hepatitis C virus (HCV, mandatory test) at study entry
Active viral infection with hepatitis B virus (HBV, mandatory test) at study entry:
a. HBsAg positive
b. HBsAg negative, anti-HBs positive and anti-HBc positive
HIV, HVS and HBV tests are mandatory
10. Uncontrolled illness including, but not limited to:
a. Active infection requiring parenteral antibiotics.
b. Uncontrolled diabetes mellitus
c. Chronic symptomatic congestive heart failure (Class NYHA III or IV).
d. Unstable angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months
e. Clinically significant cardiac arrhythmia that is symptomatic or requires treatment, or asymptomatic sustained ventricular tachycardia.
11. Prior ≥ Grade 3 allergic hypersensitivity to thalidomide.
12. Prior ≥ Grade 3 rash or any desquamating (blistering) rash while taking thalidomide.
13. Known anti-murine antibody (HAMA) reactivity or known hypersensitivity to murine antibodies.
14. Subjects with ≥ Grade 2 neuropathy.
15. Prior use of lenalidomide
16. Participation in another clinical trial within three weeks before randomization in this study

The presence of any exclusion criteria of randomization 1 or of the following criteria will exclude a subject from enrollment in the maintenance phase:
SD or PD after induction treatment determined as per Cheson 1999 criteria by investigator.
Patient treated by induction immuno-chemotherapy other than 6-8 cycle of R-CHOP21 or 2-3 cycles of R-CHOP21 / 2-3 cycles of R-HAD28 (alternating)
Patients with serious underlying medical conditions, which could impair the ability to receive maintenance treatment
Calculated creatinine clearance (Cockcroft-Gault formula or MDRD) of < 30 mL / min at screening for maintenance.
ANC is < 1,000 cells/mm^3 (1.0 x 10^9/L) at screening for maintenance
Platelet count is < 50,000 cells/mm^3 (50 x 10^9/L) at screening for maintenance


3. Registration (& randomization) of patients



Registration

Registration will be done via IWRS system of sponsor Lysarc.


4. Participating parties



Principal Investigator(s)

Mw. Dr. J.K. Doorduijn (Erasmus MC - Daniel)


Coordinating Investigator(s)

Mw. Dr. J.K. Doorduijn (Erasmus MC - Daniel)
Prof. Dr. J.C. Kluin-Nelemans (UMCG)


Statistician(s)

Mw. Dr.ir D. Chitu (Erasmus MC - Daniel)


Trial Manager(s)

Mw. H.A. Visser - Wisselaar (Erasmus MC - Daniel)


Monitor - Study Specific

Mw. T. van de Klundert (Erasmus MC - Daniel)
Mw M. Roelvink-Jansma (Erasmus MC - Daniel)


Other functions

Central Coordinator - MRD - Mw. C. Homburg (Sanquin Research)
Central Coordinator - MRD - Dhr. Dr. V.H.J. van der Velden (Erasmus MC - Centrum)
Reviewer - Pathology - Prof. Dr. J.H.J.M. van Krieken (Radboudumc)


Trial manager

N.G.J.H. Lamers (n.lamers@erasmusmc.nl)


Other functions

Central data management will be done by Lysarc.
Safety desk management will be done by Lysarc


5. Participating sites



Site
Included patients *
NL-Alkmaar-MC Alkmaar
0
NL-Amsterdam-OLVG
0
NL-Amsterdam-VUMC
0
NL-Breda-Amphia ziekenhuis, locatie Langendijk
0
NL-Delft-Reinier de Graaf Gasthuis
0
NL-Den Bosch-Jeroen Bosch ziekenhuis
0
NL-Den Haag-Hagaziekenhuis, locatie Leyweg
0
NL-Den Helder-Noordwest Ziekenhuisgroep
0
NL-Enschede-Medisch Spectrum Twente
0
NL-Goes-Admiraal de Ruyter ziekenhuis
0
Show 14 more...
* Please note that if TOP is not used to register patients for a study, the number of patients shown is zero.

6. Instruction videos



7. Download documentation / forms




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