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Clinical picture: CLL (Chronical Lymfatic Leukemia)

Trial: HOVON 140 CLL


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


HO140 news

02MAY2017_First site (AMC) has been activated! Please note that you can find all participating sites and whether or not they are activated in the section Registration & randomization of patients.

 

02MAR2017_Study has been opened recently. You can best download the HO140_ITF_02MAR2017.ZIP file to have all documents at once. In the HO140_ITF_02MAR2017_Overview folders & files.xlsx is stated which document is located at which directory. Please let me know if there are any questions (p.cornelisse@erasmusmc.nl)

 


1. Overview



Summary

A phase 3 multicenter, randomized, prospective, open-label trial of standard chemoimmunotherapy (FCR/BR) versus rituximab plus venetoclax (RVe) versus obinutuzumab (GA101) plus venetoclax (GVe) versus obinutuzumab plus ibrutunib plus venetoclax (GIVe) in fit patients with previously untreated chronic lymphocytic leukemia (CLL) without del (17p) or TP53 mutation.


Status

open


Members

GCLLSG sponsor. HOVON, SAKK, Nordic CLL group



Type of study

Prospective randomized Phase III study


Echelon level

Level D


Type of monitoring for this study

Study specific


Target number of patients

920


Date of first EC&CA submission

16-Feb-2017


Date of activation

02-Mar-2017


Approved by

NL EC: 06FEB2017
BE EC: 31MAR2017
NL CA: 19DEC2016
BE CA: 26JAN2017


Study objectives

The primary objective of the study is to evaluate the efficacy of obinutuzumab (GA101) plus venetoclax (GVe) versus standard chemoimmunotherapy (BR/FCR) [concerning MRD negativity meas-ured by flow cytometry in peripheral blood (PB) at month 15] and obinutuzumab plus ibrutinib plus venetoclax (GIVe) versus standard chemoimmunotherapy (BR/FCR) [concerning progression free survival (PFS)] in previously untreated, fit CLL patients without del(17p) or TP53 mutation.

Secondary objectives of the study are the evaluation of the efficacy of rituximab plus venetoclax (RVe) versus standard chemoimmunotherapy (BR/FCR), GVe and GIVe [concerning MRD negativity measured by flow cytometry in PB at month 15 and PFS].


2. Patient eligibility criteria



Inclusion criteria

Documented CLL requiring treatment according to iwCLL criteria.
Age at least 18 years.
Life expectancy ≥ 6 months.
Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements.
Adequate bone marrow function indicated by a platelet count >30 x10^9/L (unless directly attributable to CLL infiltration of the bone marrow, proven by bone marrow biopsy)
Creatinine clearance ≥70ml/min calculated according to the modified formula of Cockcroft and Gault (for men: GFR ≈ ((140 - age) x bodyweight) / (72 x creatinine), for women x 0, 85) or directly measured with 24hr urine collection.
- Patients with an estimated creatinine clearance just under 70ml/min may be eligible if a measured creatinine clearance (based on 24 hour urine collection or other reliable method) is > 70 ml/min. Dehydrated patients with an estimated creatinine clearance less than 70 ml/min may be eligible if a repeat estimate after adequate hydration is > 70 ml/min.
Adequate liver function as indicated by a total bilirubin≤ 2 x, AST/ALT ≤ 2.5 x the institutional ULN value, unless directly attributable to the patient’s CLL or to Gilbert’s Syndrome.
Negative serological testing for hepatitis B (HBsAg negative and anti-HBc negative; patients positive for anti-HBc may be included if PCR for HBV DNA is negative and HBV-DNA PCR is performed every month until 12 months after last treatment cycle), negative testing for hepatitis C RNA within 6 weeks prior to registration.
Eastern Cooperative Oncology Group Performance Status (ECOG) performance status 0-2.


Exclusion criteria

Any prior CLL-specific therapies (except corticosteroid treatment administered
due to necessary immediate intervention; within the last 10
days before start of study treatment, only dose equivalents of 20 mg
prednisolone are permitted).
Transformation of CLL (Richter transformation).
Decompensated hemolysis, defined as ongoing hemoglobin drop in
spite of three more concurrent treatments being administered for hemolysis
Detected del(17p) or TP53 mutation.
Patients with a history of PML.
Any comorbidity or organ system impairment rated with a single CIRS
(cumulative illness rating scale) score of 4 (excluding the
eyes/ears/nose/throat/larynx organ system), a total CIRS score of
more than 6 or any other life-threatening illness, medical condition or
organ system dysfunction that, in the investigator´s opinion, could
comprise the patients safety or interfere with the absorption or metabolism
of the study drugs (e.g, inability to swallow tablets or impaired
resorption in the gastrointestinal tract).
Urinary outflow obstruction.
Malignancies other than CLL currently requiring systemic therapies, not being treated in curative intention before (unless the malignant
disease is in a stable remission due to the discretion of the treating
physician) or showing signs of progression after curative treatment.
Uncontrolled or active infection.
Patients with known infection with human immunodeficiency virus
(HIV).
Requirement of therapy with strong CYP3A4 and CYP3A5 inhibitors/
inducers.
Anticoagulant therapy with warfarin or phenoprocoumon,
(rotation to alternative anticoagulation is allowed, but note that patients
being treated with NOAKs can be included, but must be properly
informed about the potential risk of bleeding under treatment with
ibrutinib).
History of stroke or intracranial hemorrhage within 6 months prior to
registration.
Use of investigational agents which might interfere with the study
drug within 28 days prior to registration.
Vaccination with live vaccines 28 days prior to registration.
Major surgery less than 30 days before start of treatment.
History of severe allergic or anaphylactic reactions to humanized or
murine monoclonal antibodies, known sensitivity or allergy to murine
products.
Known hypersensitivity to any active substance or to any of the excipients
of one of the drugs used in the trial.
Pregnant women and nursing mothers (a negative pregnancy test is
required for all women of childbearing potential within 7 days before
start of treatment; further pregnancy testing will be performed regularly).
Fertile men or women of childbearing potential unless: a. surgically sterile or ≥ 2 years after the onset of menopause
b. willing to use two methods of reliable contraception including one
highly effective contraceptive method (Pearl Index <1) and one
additional effective (barrier) method during study treatment and
for 18 months after the end of study treatment.
Legal incapacity.
Prisoners or subjects who are institutionalized by regulatory or court
order.
Persons who are in dependence to the sponsor or an investigator.


3. Registration (& randomization) of patients



4. Participating parties



5. Participating sites



6. Instruction videos



7. Download documentation / forms


 Protocol

 Patient Information & IC form (NL)



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