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Clinical picture: NHL (Non Hodgkin Lymphoma)

Trial: HOVON 110 FL


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


HO110 news

02JUN2017
Use of rituximab biosimilar is not allowed in this study.
27OCT2014
Fase II documenten zijn op de website geplaatst.
Deze documenten zijn per e-mail naar de deelnemende ziekenhuizen gestuurd.
23OCT2014
Phase II has started
Updated documents: 
22nov2011:
Er is een nieuwe versie CRFs (versie 5, 22NOV2012). Vanaf heden graag alleen deze versie gebruiken voor ALLE patienten.

Ook het Serious Adverse Event report form is gewijzigd. Vanaf vandaag graag alleen deze nieuwe versie (verie 3, 22NOV2012) gebruiken.


1. Overview



Summary

Efficacy and toxicity of lenalidomide and rituximab with or without bendamustine in patients ≥ 18 years with relapsed follicular lymphoma


Status

open


Members

Participating groups: HOVON and GLSG



Type of study

Prospective Phase I/II study


Type of monitoring for this study

Site evaluation visits


Target number of patients

174


Current number of patients

57


Date of activation

27-Sep-2011


Approved by

Ethics Committee AMC


Study objectives

For the phase I part of the study:
• To determine the feasibility and recommended dose level (RDL) of the combination of lenalidomide, rituximab, and bendamustine in a 28 day schedule

For the phase II part of the study:
• To study the efficacy and toxicity of the two arms of the study (LR: lenalidomide and rituximab, and LRB: lenalidomide, rituximab, and bendamustine) in patients with relapsed follicular lymphoma, and to identify the most promising of these two treatment arms.
• To determine the value of PET-CT scanning in response assessment of FL patients
• To identify predictive factors for response. For this purpose, in the non-chemotherapy-based lenalidomide-rituximab regimen and in the chemotherapy-based lenalidomide-rituximab-bendamustine regimen, various tissue–associated markers will be explored both on tumor cells and on non-malignant cells of the tumor microenvironment using tissue microarrays or primary lymphoma biopsy samples. These studies will be supported by gene expression profiling in a selection of the patients. Results will be correlated to clinical outcome as well as PET-CT results and circulating subsets of T cells and NK cells. An exploratory analysis will be performed to identify putative covariates that might indicate which patient populations would benefit most from treatment with the non-chemotherapy-based lenalidomide-rituximab regimen or from the chemotherapy-based lenalidomide-rituximab-bendamustine regimen.
• To specifically explore treatment-induced alterations in non-malignant immune cell populations. For this purpose, alterations during treatment in these populations in the peripheral blood and at the tissue level of involved lymh nodes will be performed. For the latter analysis sequential fine needle aspirations and biopsies will be performed in a selection of patients. The sequential biopsies will also be used to study the biological mechanisms of tumor cell kill.


2. Patient eligibility criteria



Inclusion criteria

• Relapsed FL grade 1, 2, 3a, see appendix A;
• Ann Arbor stage II-IV at relapse, see appendix B;
• The lymphoma at relapse must be CD20+. To establish this, and to exclude transformation to aggressive lymphoma, a biopsy at relapse is strongly recommended, see paragraph 10.2;
• A maximum of three prior systemic treatment regimens (patients that have had a prior allogeneic SCT are excluded; prior autologous SCT (if > 1 year ago) is allowed);
• Prior bendamustine is allowed, under the following conditions:
-Only one prior treatment (with a maximum of 6 cycles) with bendamustine is allowed
-Patients must have had a PR or CR following prior use of bendamustine
-Prior treatment with bendamustine must have taken place ≥24 months ago (measured from the start of prior bendamustine treatment, i.e. approximately 18 months from the end of prior bendamustine treatment)
• Subjects must have an indication for treatment based on one or more of the following criteria:
Involvement of at least 3 nodal sites, each with a diameter > 3 cm
Symptomatic splenomegaly
Bulky disease at study entry according to the GELF criteria62: nodal or extranodal mass (except spleen) > 7 cm in its greatest diameter
B-symptoms (absence or presence of fever and/or night sweats and/or unexplained loss of 10% of body weight or more in the 6 months preceding diagnosis)
Hb < 10 g/dl (6.2 mmol/l) (if caused by bone marrow infiltration and not otherwise explained)
Thrombocytopenia: platelets < 100x109/l caused by bone marrow infiltration
Organ compression syndrome (e.g. hydronephrosis caused by lymphadenopathy)
Pleural/peritoneal effusion
Symptomatic extranodal manifestations;
• Measurable disease as defined in appendix C (patients with only bone marrow involvement are therefore not eligible);
• Age ≥ 18 years;
• Able to adhere to the study visit schedule and other protocol requirements;
• WHO performance status of 0-2;
• Laboratory test results within these ranges: absolute neutrophil count ≥ 1.5x 109/l, platelet count ≥ 100x 109/l (unless bone marrow infiltration), creatinine clearance ≥ 50 ml/min, total bilirubin ≤ 30 µmol/l (1,75 mg/dl), AST & ALT ≤ 3x ULN;
• Females of childbearing potential must have a negative serum or urine pregnancy test within 10 - 14 days prior to and again within 24 hours of starting lenalidomide treatment;
• Patients must be willing and capable to use adequate contraception during and after the therapy (all men, all pre-menopausal women; see 10.2 and 12.5). Patients must be able to adhere to the requirements of the Lenalidomide Pregnancy Prevention Risk Management Plan;
• Written informed consent.


Exclusion criteria

• Rituximab-refractory patients (definition: progression during or within 6 months after rituximab containing immunochemotherapy or rituximab maintenance treatment);
• Clinical or histologic signs of transformation;
• Prior allogeneic SCT;
• Prior autologous SCT less than one year ago;
• Any prior use of lenalidomide;
• Concurrent use of other anti-cancer agents or treatments;
• Concurrent use of allopurinol, e.g. because of gout. Patients with gout are advised to switch to another anti-gout medication, because of the risk of Stevens-Johnson Syndrome observed in patients using bendamustine and allopurinol;
• Use of any other experimental drug or therapy within 28 days of baseline;
• Hepatitis B (including HBcAb) positive, Hepatitis C positive and/or HIV positive patients;
• Patients with uncontrolled autoimmune hemolytic anemia (AIHA) or autoimmune thrombocytopenia (ITP);
• Active fungal, bacterial, and/or viral infection;
• Recent vaccination for yellow fever (within 4 weeks before registration)
• Pregnant or breast-feeding females (lactating females must agree not to breast feed while taking lenalidomide);
• Known hypersensitivity and/or serious adverse reactions to lenalidomide or similar drugs;
• Intolerance of exogenous protein administration, or known allergy to murine products;
• Uncontrolled hyperthyroidism or hypothyroidism;
• Neuropathy ≥ grade 2 at time of inclusion;
• Clinically symptomatic severe cardiac dysfunction (NYHA III-IV, see appendix G);
• Clinically symptomatic severe pulmonary dysfunction;
• Severe neurologic or psychiatric diseases;
• Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection);
• History of active malignancy during the past 5 years with the exception of basal carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, prostate cancer (TNM stage of T1a or T1b);
• Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.


3. Registration (& randomization) of patients



Registration

Eligible patients should be registered before start of treatment. Patients need to be registered at the HOVON Data Center by one of the following options:
Trial Online Process (TOP, https://www.hdc.hovon.nl/top) Monday through Sunday, 24 hours/day. A logon to TOP can be requested at the HOVON Data Center for participants.
By faxing the completed registration/randomization CRF +31.10.7041028 Monday through Friday, from 09:00 to 17:00 CET
By phone +31.10.7041560 Monday through Friday, from 09:00 to 17:00 CET

FOR PHASE I PATIENTS CAN ONLY BE REGISTERED BY HOVON DATA CENTER


Registration criteria

The following information will be requested:



Protocol number
Institution name
Name of caller/responsible investigator
Local patient code (optional)- Gender
Date of birth
Date written informed consent
Pathology number (relapse)
Original pathology laboratory (relapse)
Specific items patient gives consent for (see ICF)
Planned date start cycle 1
Eligibility criteria, please make sure that you have detailed information available on disease status and prior treatment
Stratification factors


4. Participating parties



Principal Investigator(s)

Mw. M.J. Kersten (AMC)


Co-Investigator(s)

Prof.Dr. C. Buske (University Hospital of Ulm)
Mw. Dr. J.K. Doorduijn (Erasmus MC - Daniel)
Prof. Dr. M. Dreyling (Klinikum der Universität München)
Prof. Dr. A. Hagenbeek (AMC)


Coordinating Investigator(s)

Prof. Dr. M. Dreyling (Klinikum der Universität München)
Dr. K. Linton (Christie NHS Foundation Trust)


Statistician(s)

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


Other functions

Central Coordinator - Special Investigations - C. Pott (UH Schleswig-Holstein im SK Kiel)
Central Coordinator - Special Investigations - Mw. M. Spiering (AMC)
Central Pharmacist - Mw. Dr. E.M. Kemper (AMC)
Reviewer - Pathology - HOP pathologist (VUMC)
Reviewer - Pathology - Mw. Dr. D. de Jong (VUMC)


Trial manager

I. Meulendijks (L.Meulendijks@erasmusmc.nl)


5. Participating sites



Site
Included patients *
DE-Amberg-Klinikum St. Marien
0
DE-Bayreuth-Klinikum Bayreuth
1
DE-Dessau-Städtisches Klinikum Dessau
0
DE-Dresden-Gemeneinschaftspraxis für Innere Medizin
1
DE-Eschweiler-St. Antonius Hospital Eschweiler
0
DE-Eschweiler-St. Antonius Hospital Eschweiler
0
DE-Essen-Universitaetsklinikum Essen
1
DE-Idar-Oberstein-Klinikum Idar-Oberstein GmBH
0
DE-Kiel-UH Schleswig-Holstein im SK Kiel
0
DE-Lebach-Caritas Onkologisches Zentrum
0
Show 39 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


 Protocol



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