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Acute Myeloid LeukemiaPhase 1/2CIARANCT01534702

Dose Escalation of Clofarabine in Combination With Cytarabine and Idarubicin as Induction Therapy in High Risk AML

A Phase 1/2 study testing clofarabine, cytarabine, idarubicin in people with Acute Myeloid Leukemia, run by Hannover Medical School at 7 sites in Germany.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
clofarabine, cytarabine, idarubicin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
7 sitesGermany
Study dates
Jan 2012to Sep 2015
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • Written informed consent
  • No previous cytotoxic chemotherapy for the treatment of AML (exception: oral hydroxyurea for up to 5 days during screening/baseline to control hyperleukocytosis)
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  • 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
  • Capable of understanding the investigational nature, potential risks and benefits of the study
  • 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
  • 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
  • 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

Who cannot join

  • Current concomitant chemotherapy, radiation therapy or immunotherapy not defined in the study protocol
  • 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
  • Participation in a clinical trial within 30 days before inclusion in this study or concurrent to this study.
  • Bleeding disorder independent of AML
  • Patients with uncontrolled systemic fungal, bacterial, viral or other infection (defined as persistent disease signs/symptoms without improvement despite appropriate antibiotics or other treatment)
  • HIV Infection
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  • Pregnant or lactating women
  • 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
  • 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.
  • Known hypersensitivity to any of the investigational medical products

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

Germany7 sites, 7 recruiting

  • Universitätsklinikum Düsseldorf

    Düsseldorf, 40225

    Andrea Kuendgen, MD, andrea.kuendgen@med.uni-duesseldorf.de

    Andrea Kuendgen, MD

    Not yet recruiting

  • Klinikum Essen-Werden

    Essen, 45239

    Mohammad Wattad, MD, m.wattad@kliniken-essen-sued.de

    Mohammad Wattad, MD

    Recruiting

  • Universitätsklinikum Freiburg

    Freiburg im Breisgau, D-79106

    Michael Luebbert, MD, luebbert@mm11.ukl.uni-freiburg.de

    Michael Luebbert, MD

    Recruiting

  • Universitätsklinikum Hamburg-Eppendorf

    Hamburg, 20246

    Walter Fiedler, MD, fiedler@uke.uni-hamburg.de

    Walter Fiedler, MD

    Not yet recruiting

  • Hannover Medical School

    Hanover, D-30625

    Juergen Krauter, MD, +49-511-532-3720, Krauter.Juergen@MH-Hannover.de

    Juergen Krauter, MD

    Recruiting

  • Klinikum Rechts der Isar

    München, 81675

    Justus Duyster, justus.duyster@lrz.tum.de

    Justus Duyster, MD

    Not yet recruiting

  • Universitätsklinikum Ulm

    Ulm, 89081

    Richard Schlenk, MD, Richard.Schlenk@uniklinik-ulm.de

    Richard Schlenk, MD

    Not yet recruiting

Other trials in Germany

About this study

Official 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)

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.

Being tested
clofarabine, cytarabine, idarubicin
Keywords
Acute Myeloid Leukemia, chemotherapy, clofarabine
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • clofarabine, cytarabine, idarubicinDrug

    Treatment is stratified according to patients age (< 60 years vs. ≥ 60 years).

    Medication:

    Patients < 60 years:

    • idarubicin 7.5 mg/m2 iv, days 1 + 3
    • cytarabine 750 mg/m2 iv, days 1 to 5

    Patients ≥ 60 years:

    • idarubicine 6 mg/m2 iv, days 1 + 3
    • cytarabine 750 mg/m2 iv, days 1 to 5

    Clofarabine will be given in escalating doses to cohorts of at least three patients:

    Clofarabine:

    • level -1: 15 mg/m2 iv, days 1 to 5
    • level 1: 20 mg/m2 iv, days 1 to 5
    • level 2: 25 mg/m2 iv, days 1 to 5
    • level 3: 30 mg/m2 iv, days 1 to 5
    • level 4: 35 mg/m2 iv, days 1 to 5

    Patients will be recruited according to a 3+3 design. New cohorts will be initiated depending on toxicity of the previous cohort during the first induction cycle. Enrollment will begin with dose level 1.

Study groups in NCT01534702
Study groupRoleWhat they receive
TreatmentExperimentalNot described
Receives: Drug: clofarabine, cytarabine, idarubicin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. maximal tolerated dose of clofarabine in combination with cytarabine and idarubicin

    maximal tolerated dose of clofarabine in combination with cytarabine and idarubicin in the therapy of previously untreated AML and high risk for induction failure

    Measured: six weeks

Secondary outcomes (7)

  1. complete remission rate

    complete remission rate after two cycles of induction therapy

    Measured: 12 weeks

  2. relapse-free, event-free and overall survival

    Measured: 4 years

  3. blast reduction in the bone marrow after the first induction cycle

    Measured: 15 days

  4. duration of aplasia

    Measured: 12 weeks

  5. therapy-associated morbidity and mortality

    Measured: 12 weeks

  6. course of molecular and cytogenetic markers during chemotherapy

    molecular and cytogenetic markers will be evaluated by cytognetic analysis and molecular techniuques (e.g. RT-PCR)

    Measured: four years

  7. fraction of patients who receive an allogeneic stem cell transplantation in first complete remission

    Measured: four years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Feb 2012 (estimated)
  2. Study startJan 2012
  3. Primary completionApr 2013 (estimated)
  4. Study completionSep 2015 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01534702
Sponsor's protocol ID
KS-2009-003
Other IDs
2010-021719-18
Acronym
CIARA
Status last verified
Feb 2012
First submitted
14 Feb 2012
Last updated
20 Feb 2012
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing clofarabine, cytarabine, idarubicin in people with Acute Myeloid Leukemia, run by Hannover Medical School at 7 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 20 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

maximal tolerated dose of clofarabine in combination with cytarabine and idarubicin (time frame: six weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01534702.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2012.

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