Trial document





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

  DRKS00003806

Trial Description

start of 1:1-Block title

Title

Phase I/II Study on Cytarabine and Idarubicin Combined With Escalating Doses of Clofarabine as Induction Therapy in Patients With Acute Myeloid Leukemia and High Risk for Induction Failure (AMLSG 17-10)

end of 1:1-Block title
start of 1:1-Block acronym

Trial Acronym

CIARA

end of 1:1-Block acronym
start of 1:1-Block url

URL of the Trial

[---]*

end of 1:1-Block url
start of 1:1-Block public summary

Brief Summary in Lay Language

With current chemotherapy protocols, in 60-80% of patients with acute myeloid leukemia (AML)
the leukemic blasts in the bone marrow can be reduced to < 5%. This is called "complete
remission (CR)" and is the prerequisite for cure of the disease. During the last years,
several genetic and biologic risk factors for the achievement of CR have been defined, and
the remission rates vary considerably between patient groups with different risk profiles.
On one hand, patients with certain chromosomal or molecular aberrations have very high CR
rates of approximately 90%. Moreover, in some of these patients, molecularly targeted
therapies for specific genetic aberrations are currently evaluated in clinical trials.
However, these genetic aberrations account for only 50-60% of the overall patient population
in AML. The remaining patients have a significantly inferior CR rate of only 50-60% with 30%
resistant disease after two cycles of standard induction chemotherapy. In conclusion, there
is need for improved induction regimens in a large number of adult patients with AML. An
improved CR rate in this patient population will increase the number of patients eligible
for intensive consolidation such as an allogeneic stem cell transplantation and might
thereby be the basis for a better overall outcome. However, there is no clear evidence that
this goal can be achieved with the currently available chemotherapy protocols. Clofarabine
(2-chloro-2-fluoro-deoxy-9-D-arabinofuranosyladenine) is a nucleoside analogon which
combines properties of fludarabine and cladribine. Due to the lack of neurological side
effects, clofarabine could be explored in higher doses than other nucleoside analogues and
has shown considerable antileukemic activity in patients with relapsed or refractory acute
leukemias and elderly AML patients alone or in combination with cytarabine. In addition, the
combination of clofarabine, cytarabine and idarubicin has produced promising results with
acceptable toxicity in patients with relapsed or refractory AML. Based on these initial
studies, there is need for a further optimization of the clofarabine dose in this
combination. The aim of the AMLSG 17-10 study is therefore to evaluate the tolerability and
safety of increasing doses of clofarabine in combination with idarubicin/cytarabine in
patients with high risk AML defined by the genetic and molecular risk profile.

end of 1:1-Block public summary
start of 1:1-Block scientific synopsis

Brief Summary in Scientific Language

[---]*

end of 1:1-Block scientific synopsis
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00003806
  •   2012/04/24
  •   2012/02/14
  •   yes
  •   [---]*
  •   [---]*
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  •   2010-021719-18 
  •   NCT01534702  (ClinicalTrials.gov)
  •   KS-2009-003  (Hannover Medical School)
  •   2010-021719-18 
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   Acute Myeloid Leukemia
  •   C92.0 -  Acute myeloid leukaemia
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   Drug: clofarabine, cytarabine, idarubicin
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Interventional
  •   [---]*
  •   Single arm study
  •   Open (masking not used)
  •   [---]*
  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   I-II
  •   [---]*
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

- maximal tolerated dose of clofarabine in combination with cytarabine and idarubicin; time frame: six weeks; maximal tolerated dose of clofarabine in combination with cytarabine and idarubicin in the therapy of previously untreated AML and high risk for induction failure

end of 1:1-Block primary endpoint
start of 1:1-Block secondary endpoint

Secondary Outcome

- complete remission rate; time frame: 12 weeks; complete remission rate after two cycles of induction therapy
- relapse-free, event-free and overall survival; time frame: 4 years
- blast reduction in the bone marrow after the first induction cycle; time frame: 15 days
- duration of aplasia; time frame: 12 weeks
- therapy-associated morbidity and mortality; time frame: 12 weeks
- course of molecular and cytogenetic markers during chemotherapy; time frame: four years; molecular and cytogenetic markers will be evaluated by cytognetic analysis and molecular techniuques (e.g. RT-PCR)
- fraction of patients who receive an allogeneic stem cell transplantation in first complete remission; time frame: four years

end of 1:1-Block secondary endpoint
start of 1:n-Block recruitment countries

Countries of Recruitment

  •   Germany
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  •  
  •  
  •  
  •  
  •  
  •  
  •  
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment

Recruitment

  •   [---]*
  •   2012/01/31
  •   60
  •   Multicenter trial
  •   National
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

Additional Inclusion Criteria

1. Patients with newly diagnosed AML according to WHO classification and aged ≥ 18 years
eligible for an intensive induction chemotherapy with with the following
characteristics:

- absence of a t(15;17), t(8;21), inv(16)/t(16;16) and the respective fusion
transcripts PML-RARA, RUNX1-RUNX1T1 and CBFB-MYH11

- absence of an activating FLT3-mutation (FLT3-ITD or TKD-mutation)

- absence of an NPM1 exon12 mutation

2. Written informed consent

3. No previous cytotoxic chemotherapy for the treatment of AML (exception: oral
hydroxyurea for up to 5 days during screening/baseline to control hyperleukocytosis)

4. Adequate renal and hepatic functions as indicated by the following laboratory values:

- Serum creatinine > upper limit of normal (ULN) or glomerular filtration rate
(GFR) > 60 mL/min/1.73 m2, respectively

- Serum bilirubin < 1.5 x ULN

- Aspartate aminotransferase (AST/SGOT)/ alanine aminotransferase (ALT/SGPT) < 2.5
x ULN

- Alkaline phosphatase (ALP) < 2.5 x ULN

5. Capable of understanding the investigational nature, potential risks and benefits of
the study

6. Women of childbearing potential must have a negative serum pregnancy test with a
sensitivity of at least 25 MIU/ml within 72 hours prior to start of IMP treatment

7. Female patients must meet one of the following criteria:

- For female patients > 50 years of age at the day of inclusion: Menopause since
at least 1 year

- Female patients < 50 years of age at the day of inclusion who meet all of the
following criteria:

- menopause since at least 1 year

- serum FSH levels > 40 MIU/mL

- serum estrogen levels < 30 pg/ml or negative estrogen test

- 6 weeks after surgical sterilization by bilateral tubal ligation or bilateral
ovariectomy with or without hysterectomy

- Correct use of two reliable contraception methods from the time of
screening/baseline and during the study for a minimum of 90 days after the last
administration of study medication. This includes every combination of a
hormonal contraceptive (such as oral, injection, transdermal patch, implant,
cervical ring) or of an intrauterine device (IUD) with a barrier method
(diaphragm, cervical cap, Lea contraceptive, femidom or condom) or with a
spermicide. In case the patient takes hormone preparations for suppression of
menstruation during the period of aplasia, a suitable and effective method of
contraception has to be discussed with the investigator and used by the patient

- General sexual abstinence from the time of screening/baseline, during the study
until a minimum of 90 days after the last administration of study medication

- Having only female sexual partners

- Monogamous relationship with sterile male partner

8. Male patients must meet one of the following criteria:

- 6 weeks after surgical sterilization by vasectomy

- Correct use of two reliable contraception methods from the time of
screening/baseline and during the study for a minimum of 90 days after the last
administration of study medication. This includes every combination of a
hormonal contraceptive (such as oral, injection, transdermal patch, implant,
cervical ring) or of an IUD with a barrier method (diaphragm, cervical cap, Lea
contraceptive, femidom or condom) or with a spermicide.

- General sexual abstinence from the time of screening/baseline, during the study
until a minimum of 90 days after the last administration of study medication

- Having only male sexual partners

- Monogamous relationship with sterile female partner

end of 1:1-Block inclusion criteria add
start of 1:1-Block exclusion criteria

Exclusion Criteria

1. Current concomitant chemotherapy, radiation therapy or immunotherapy not defined in
the study protocol

2. Use of investigational agents within 30 days or any anticancer therapy within 2 weeks
before study entry with the exception of oral hydroxyurea. The patient must have
recovered from all non-hematological acute toxicities from any previous therapy

3. Participation in a clinical trial within 30 days before inclusion in this study or
concurrent to this study.

4. Bleeding disorder independent of AML

5. Patients with uncontrolled systemic fungal, bacterial, viral or other infection
(defined as persistent disease signs/symptoms without improvement despite appropriate
antibiotics or other treatment)

6. HIV Infection

7. Pregnant or lactating women

8. Any significant concurrent disease, illness, psychiatric disorder or history of
serious organ dysfunction that would compromise patient safety or compliance,
interfere with consent, study participation, follow up, or interpretation of study
results

9. Diagnosis of another malignancy, unless the patient is disease-free for at least 3
years following the completion of curative intent therapy, with the following
exceptions:

- Myelodysplastic syndrome (MDS) in patients with AML after MDS according to the
WHO classification

- Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical
intraepithelial neoplasia, regardless of the disease-free duration, are eligible
for this study if definitive treatment for the condition has been completed.

10. Known hypersensitivity to any of the investigational medical products

end of 1:1-Block exclusion criteria
start of 1:n-Block addresses

Addresses

  • start of 1:1-Block address primary-sponsor
    • Hannover Medical School
    end of 1:1-Block address primary-sponsor
    start of 1:1-Block address contact primary-sponsor
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact primary-sponsor
  • start of 1:1-Block address other
    • Hannover Clinical Trial Center GmbH
    end of 1:1-Block address other
    start of 1:1-Block address contact other
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact other
  • start of 1:1-Block address other
    • Genzyme, a Sanofi Company
    end of 1:1-Block address other
    start of 1:1-Block address contact other
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact other
  • start of 1:1-Block address scientific-contact
    • Hannover Medical School
    • Juergen Krauter, MD 
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • Hannover Medical School
    • Juergen Krauter, MD 
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact public-contact
end of 1:n-Block addresses
start of 1:n-Block material support

Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact materialSupport
end of 1:n-Block material support
start of 1:1-Block state

Status

  •   Recruiting ongoing
  •   [---]*
end of 1:1-Block state
start of 1:n-Block publications

Trial Publications, Results and other Documents

  • [---]*
end of 1:n-Block publications
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 .
  •   128
  •   2013/10/30
* This entry means the parameter is not applicable or has not been set.