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Clinical picture: CLL (Chronical Lymfatic Leukemia)


1. Overview
Study details
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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HO121 closure


The HO121 study is closed

1. Overview


A phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study of the efficacy ans safety of lenalidomide (Revlimid®) as maintenance therapy for high-risk patients with chronic lymphocytic leukemia following the first-line therapy




Leading group: GCLLSG

Study details

Type of study

Prospective randomized Phase III study

Echelon level

Level D

Type of monitoring for this study

Study specific

Target number of patients


Current number of patients


Date of activation


Approved by


Study objectives

Primary Objective
To compare the efficacy of lenalidomide versus placebo maintenance therapy

The primary efficacy objective of this study is to demonstrate superioity of lenalidomide maintenance therapy over placebo maintenance therapy in prolonging PFS, for subjects with a high risk of early progression following first-line treatment. All subjects, including both subjects who do and do not achieve MRD negativity will be treated up to disease progression with maintenance therapy with the objective to demonstrate prolongation of PFS for the lenalidomide arm.

Secondary Objective;
To evaluate the prolongation of overall survival (OS) of lenalidomide versus placebo maintenance therapy
To evaluate the safety of lenalidomide versus placebo maintenance therapy.

2. Patient eligibility criteria

Inclusion criteria

1. Must understand and voluntarily sign an informed consent form.
2. Age ≥ 18 years at the time of signing the informed consent form.
3. Must be able to adhere to the study visit schedule and other protocol requirements.
4. Must have a documented diagnosis of CLL (IWCLL guidelines for the diagnosis and treatment of chronic lymphocytic leukemia1).
5. Must have been treated with one of the first line induction therapies: fludarabine/cyclophosphamide/rituximab, or bendamustine/rituximab or fludarabine/rituximab or fludarabine/cyclophosphamide,(in case of
hypersensitivity reactions to Rituximab).
6. Must have achieved a response of at least PR (IWCLL guidelines for the diagnosis and treatment of chronic lymphocytic leukemia [Hallek, 2008])
following completion (minimum 4 cycles) of first-line induction therapy prior to randomization (documentation of response status must be available). and have either:
a. MRD levels in the peripheral blood at final restaging of ≥10^2 or
b. MRD levels in the peripheral blood ≥10^4 - <10^2 combined with at least one of the following factors:
• an unmutated IGHV-status
• 17p-deletion or
• TP53 mutation1
7. Must have completed last cycle of at least 4 cycles of first-line induction no less than 8 weeks (56 days) and no greater than 20 weeks (140 days)
prior to randomization.
8. Subjects who completed first line induction treatment with less than 6 but at least 4 cycles should document reason for early discontinuation
9. Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of ≤2.
10. Negative serological Hepatitis B test, negative testing of Hepatitis C RNA, negative HIV test within 6 weeks prior to randomization.
11. Females of childbearing potential (FCBP)†
• Have two negative medically supervised pregnancy tests prior to starting of study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study therapy. This applies even if the subject practices complete and continued sexual abstinence.
• Either commit to continued abstinence from heterosexual intercourse (which must be reviewed on a monthly basis) or agree to use, and be able to comply with, two reliable forms of effective
contraception simultaneously to achieve a PEARL-Index <1 without interruption (Highly effective methods: Intrauterine device (IUD), Hormonal (birth control pills, injections, implants), Tubal ligation,Partner’s vasectomy, Additional effective methods: Male condom,

Definition: This protocol defines a female of childbearing potential as a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing
potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
CLL M1 Page 8 of 101
CLLM1 Protocol of the DCLLSG version 2.1of 4th June 2012 University of Cologne Diaphragm, Cervical Cap), 28 days prior to starting study drug, during the study therapy (including dose interruptions), and for 28 days after discontinuation of study therapy.
12. Male subjects must:
• Agree to use a condom during sexual contact with a FCBP, even if they have had a vasectomy, throughout study drug therapy, during any dose interruption and after cessation of study therapy.
• Agree to not donate semen during study drug therapy and for a period after end of study drug therapy.
13. All subjects must:
• Have an understanding that the study drug could have a potential teratogenic risk.
• Agree to abstain from donating blood while taking study drug therapy and following discontinuation of study drug therapy.
• Agree not to share study medication with another person.
• Be counseled about pregnancy precautions and risks of fetal exposure.
14. Willingness to inform the general practicioner

Exclusion criteria

1. A CIRS Score of more than 6 or a single score of 4 for an organ system limiting the ability to receive an intensive therapy for CLL
2. Active infections requiring systemic antibiotics.
3. Systemic infection CTC grade 3 or 4 that has not resolved > 2 months prior to randomization in spite of adequate anti-infective therapy.
4. Autologous or allogeneic bone marrow transplant as first line therapy.
5. Pregnant or lactating females.
6. Systemic treatment for CLL in the interval between completing the last cycle of first-line induction therapy and randomization.
7. Participation in any clinical study or having taken any investigational therapy which would interfere with the study drug for a disease other than CLL within 28 days prior to initiating maintenance therapy.
8. Known presence of alcohol and/or drug abuse.
9. Central nervous system (CNS) involvement as documented by spinal fluid cytology or imaging. Subjects who have signs or symptoms suggestive of leukemic meningitis or a history of leukemic meningitis must have a lumbar puncture procedure performed within two weeks prior to randomization.
10. Prior history of malignancies, other than CLL, unless the subject has been free of the disease for ≥5 years.
11. History of renal failure requiring dialysis.
12. Prior therapy with lenalidomide.
13. Any of the following laboratory abnormalities:
• Calculated (method of Cockroft-Gault) creatinine clearance of <60 mL/min
• Absolute neutrophil count (ANC) < 1,000/μL (1.0 X 109/L)
• Platelet count < 50,000/μL (50 X 109/L)
• Serum aspartate aminotransferase (AST)/serum glutamicoxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum
glutamate pyruvate transaminase (SGPT) > 3.0 x upper limit of normal (ULN)
• Serum total bilirubin > 2.0 mg/dL (with the exception of Gilbert’s Syndrome)
14. Uncontrolled hyperthyroidism or hypothyroidism
15. Venous thromboembolism within one year
16. ≥ Grade-2 neuropathy
17. Uncontrolled autoimmune hemolytic anemia or thrombocytopenia
18. Disease transformation (active) (i.e. Richter’s Syndrome, prolymphocytic leukemia)
19. Known allergy to allopurinol, if the subject has bulky disease
20. Prisoners or subjects who are institutionalized by regulatory or court order or persons who are in dependence to the sponsor or an investigator

3. Registration (& randomization) of patients


Registration and randomization will be accomplished by an IVRS/IWRS Designated research personnel at the investigational sites will be assigned password protected, coded identification
numbers, which gives them authorization to call into the IVRS/IWRS to enroll subjects. The system will present a menu of questions by which the research
personnel will identify the subject and confirm eligibility. When all questions have been answered, including questions regarding the results of pregnancy tests for FCBP, the IVRS/IWRS will assign a subject number and study drug to
the eligible subject. IVRS/IWRS will fax a confirmation of registration and drug
assignment for each subject to the site and the study office of the GCLLSG.
Subjects will be randomized (2:1) to receive lenalidomide or placebo.

Registration criteria

The following information will be requested:

Registration should take place prior to start of firstline

Randomization must occur no less than 8 weeks (56 days) and no greater than20 weeks (140 days) from the completion of the first-line induction therapy
received by the subject in order for the subject to be eligible for enrollment into this study.

4. Participating parties

Principal Investigator(s)

Ms. Dr. B. Eichhorst (Klinikum der Universität zu Köln)

Monitor - Study Specific

Mw. W.M. Keller (Erasmus MC - Daniel)

5. Participating sites

Included patients *

* 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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