Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00005774

Trial Description

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Title

Ofatumumab Induction and Maintenance in Elderly Patients With Poor Risk CLL in the Context of Allogeneic Transplantation(CLL-X4 Trial)

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

To study the safety and efficacy of anti-CD20 blockade with ofatumumab in the context of
allogeneic HCT in CLL

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Brief Summary in Scientific Language

The goal of the study is to investigate the safety and efficacy of a consequent anti-CD20
therapy with the antibody ofatumumab in the context of allogeneic HCT. Allogeneic HCT itself
is not a study intervention and is triggered by the availability of an HLA-compatible stem
cell donor. The study is divided into an induction part and a maintenance part. During
induction where the antibody is combined with high dose dexamethasone, the main goal is to
reduce the tumor load prior to allogeneic HCT. Patients who achieved disease control (CR, PR
and SD) by the antibody proceed to maintenance therapy with the antibody. Patients with
progressive disease go off study. The idea behind maintenance therapy is that ofatumumab may
contribute to tumor control early after allogeneic stem cell transplantation while T-cell
based graft-versus leukemia effects are still not fully established. External tumor control
could lower the pressure to taper immunosuppressive drugs early after transplantation and
could thereby indirectly contribute to better GVHD-prophylaxis. Furthermore, anti-CD20
antibodies have proven activity in the treatment of chronic GVHD. In summary, the concept of
a consequent CD20 blockade in the context of allogeneic transplantation could result in
better leukemic control and better GVHD prophylaxis, which is a highly attractive goal.

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Organizational Data

  •   DRKS00005774
  •   2014/02/14
  •   2012/12/18
  •   yes
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Secondary IDs

  •   2012-001947-31 
  •   NCT01809847  (ClinicalTrials.gov)
  •   TUD-CLL-X4-054  (Technische Universität Dresden)
  •   2012-001947-31 
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Health Condition or Problem studied

  •   Chronic Lymphatic Leukemia
  •   C91.1 -  Chronic lymphocytic leukaemia of B-cell type
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Interventions/Observational Groups

  •   Drug: Ofatumumab
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Characteristics

  •   Interventional
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  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   II
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Primary Outcome

- Response rate after induction therapy; time frame: week 9; efficacy analysis of anti-CD20 blockade with ofatumumab
- rate of MRD-negative patients; time frame: baseline, week 9, month 14; rate of MRD-negative patients who did not experience relapse, progression or death within the first 14 months after study enrollment

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Secondary Outcome

- Rate of allogeneic HCT; time frame: month 9; Rate of patients who reach allogeneic HCT if HLA-matched donor is available
- adverse drug reactions grade III/IV; time frame: week 1 till week 9; month 4 till month 9; month 12; month 14; untill 30 days after last administration of the study medication
- Overall, event-, and progression free survival; time frame: week 1 till week 9; month 4 till month 9; month 12; month 14; up to 5 years follow-up
- relapse incidence; time frame: month 4 till month 9; month 12; month 14; up to 5 years follow-up
- non-relapse mortality; time frame: week 1 till week 9; month 4 till month 9; month 12; month 14; up to 5 years follow-up
- Incidences of acute and chronic GVHD; time frame: during maintenance therapy; month 12, month 14; up to 5 years follow-up; provided that allogeneic HCT was conducted

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

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Recruitment

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  •   2013/03/31
  •   79
  •   Multicenter trial
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Inclusion Criteria

  •   Both, male and female
  •   56   Years
  •   no maximum age
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Additional Inclusion Criteria

- Diagnosis of CLL according to WHO criteria (Hallek 2008) confirmed by flow cytometry
of peripheral blood or bone marrow

- Age > 55 years

- Poor-risk disease according to the EBMT CLL Transplant Consensus

- Non-response or early relapse (within 12 months) after purine
analogue-containing therapy

- Relapse (within 24 months) after purine analogue combination therapy or
treatment of similar efficacy (ie, autologous stem cell transplantation)

- p53 deletion/mutation (del 17p-) requiring treatment

- Measurable disease in the peripheral blood defined by a minimum clonal lymphocyte
count of 0.5 GPT/L at the time of study inclusion

- Medically fit patients eligible for allogeneic HCT

- Informed consent for related and unrelated donor search and the goal to perform
allogeneic HCT

- Sexually mature males must agree to use adequate and medically accepted method of
contraception throughout the study if their sexual partners are woman of child
bearing potential (WOCBP) WOCBP must be using an adequate and medically accepted
method of contraception to avoid pregnancy throughout the study and for at least 3
months after the study.

- WOCBP includes any female that has experienced menarche and who has not undergone
successful surgical sterilization (hysterectomy, bilateral tubal ligation or
bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea >12
consecutive months); or woman on hormone replacement therapy (HRT) with documented
serum follicle stimulating hormone (FSH) level >35mlU/mL.

- WOCBP must have a negative serum or urine pregnancy test prior to the start of the
study.

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Exclusion Criteria

- Richter's transformation in current relapse or active disease

- Prior allogeneic HCT

- Treatment with any known non-marketed drug substance or experimental therapy within 5
terminal half lives or 4 weeks prior to enrollment, whichever is longer, or
participation in any other interventional clinical study

- Non-response to monotherapy with ofatumumab prior to study inclusion

- Clinically significant cardiac disease including unstable angina, acute myocardial
infarction within six months prior to randomization, congestive heart failure (left
ventricular ejection fraction < 50%)

- Abnormal renal function defined by an estimated GFR < 50 ml/min

- Abnormal lung function tests defined by a DLCO <50%, FEV1%VC <70% despite appropriate
treatment

- Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg or HBcAb

- Positive serology for hepatitis C (HC) defined as a positive test for anti-HCV,
confirmed by PCR

- Screening laboratory values:

- total bilirubin >1.5 times upper normal limit (unless due to AIHA or a known
history of Gilbert's disease)

- ALT or AST >2.5 times upper normal limit

- Gamma glutamyl transpeptidase (GGT) >2.5 times upper normal limit (unless due to
disease involvement of the liver)

- Other past or current hematologic or solid organ malignancy. Subjects who have been
free of malignancy for at least 3 years, or have a history of completely resected
non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible.

- Male subjects unable or unwilling to use adequate contraception methods from study
start to one year after the last dose of protocol therapy.

- Pregnant or lactating woman

- Significant concurrent, uncontrolled medical condition including, but not limited to,
renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or
psychiatric disease which in the opinion of the investigator may represent a risk for
the patient.

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Addresses

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    • Technische Universität Dresden
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    • University Hospital Dresden
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    • University Hospital Ulm
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    • University of Schleswig-Holstein
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    • University Hospital of Cologne
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    • Universitätsklinikum Carl Gustav Carus, Medizinische Klinik und Poliklinik I, 01307 Dresden
    • Johannes Schetelig, PD Dr. med. 
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    • Johannes Schetelig, PD Dr. med. 
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Sources of Monetary or Material Support

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    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   3
  •   2014/11/27
* This entry means the parameter is not applicable or has not been set.