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Multicentric Phase II Trial, Prospective, Open, Single Group, to Discuss Induction Therapy With a Combination of Clofarabine and Low-dose Cytarabine Followed by Consolidation Therapy With Clofarabine and Low-dose Cytarabine for the Treatment of AML Patients Age Greater Than or Equal to 60 Years


Phase 2
60 Years
N/A
Open (Enrolling)
Both
Acute Myelogenous Leukemia

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Trial Information

Multicentric Phase II Trial, Prospective, Open, Single Group, to Discuss Induction Therapy With a Combination of Clofarabine and Low-dose Cytarabine Followed by Consolidation Therapy With Clofarabine and Low-dose Cytarabine for the Treatment of AML Patients Age Greater Than or Equal to 60 Years


This protocol corresponds to a multicenter, phase II, open, non randomized, designed to
determine the efficacy of clofarabine and low-dose cytarabine combination in AML patients
older than or equal to 60 years.

The trial is divided into pre-treatment and treatment (cycle / s of induction and
consolidation) periods.The induction cycle consist of clofarabine at 20 mg/m2/day
intravenously for 5 consecutive days plus cytarabine subcutaneously at 20 mg/m2/day for 14
consecutive days. If patients do not achieve CR they will receive a second course of
induction with the same pattern. Consolidation cycles consist of clofarabine intravenously
at 15 mg/m2/day for 5 consecutive days plus cytarabine at 20 mg/m2/day subcutaneously for 7
consecutive days. Patients will receive a maximum of 12 cycles of clofarabine and LDAC. The
monitoring phase of survival is made by clinical practice and will continue until all
patients have either died or survived two years after the end of treatment visit.

There will be 75 patients older than or equal to 60 years. Patients will be evaluated over
the following periods: Pre-treatment and treatment (induction and consolidation).

Pre-treatment phase: includes enrolment visit in which the patient completes the written
informed consent to participate in the study.

There will be a selection of patients who have given their written informed consent to join
the clinical trial. They must meet all the inclusion criteria and no exclusion.

Treatment phase: Patients should begin treatment within 14 days after signing the informed
consent form (ICF). Selection period begins when the ICF is signed and the inclusion period
begins when the patient first receives the study drug (ie Day 1 of the induction cycle).

Safety will be evaluated by monitoring all adverse events haematological and not
haematological related with the drug's study.

The final visit of treatment will take place at least 45 days after the last dose of study
drug administration.

Patients who leave the study prematurely, should have the end of treatment visit within 2
weeks after the decision not to continue to administer the study drug. The final visit
should take place within 2 weeks after the visit of the last cycle of treatment.

Off protocol, after making the final visit of, all patients receiving at least one dose of
study drug will be subject to monitoring by normal clinical practice, for a minimum of two
years from the final visit or until his death

Follow up phase:

The maximum follow-up for all patients is 2 years from the final visit of the last patient
included and be conducted on a monthly basis during the first year and quarterly during the
second at least, notwithstanding that there may be more visits at discretion of each centre
or depending on the clinical features.


Inclusion Criteria:



1. Diagnosis of AML (de novo, secondary, or hematological disorder), according to WHO
criteria.

2. Older than or equal to 60 years

3. ECOG performance status 0-2

4. At least one of the following factors:

- Older than or equal to 70 years

- Prior hematological disorder (AHD)

- ECOG performance status 2

- Unfavorable karyotype (ie, adverse) defined as any cytogenetic profile except
the presence of any of the following:

t(8;21)(q22;q22) inv(16)(p13q22) or t(16;16)(p13;q22) t(15;17)(q22;q12) and
variants

5. Provide written informed consent form.

6. Being able to comply with study procedures and follow-up evaluations.

7. Not to be fertile or willing to use a method of birth control during the study until
the end of the last visit of the treatment.

8. Adequate renal and hepatic function as follows:

- Total bilirubin <= 1,5 x upper of institutional normal limit (ULN) and

- AST y ALT <=2,5 x ULN and

- Serum creatinine <=1,0 mg/dL of serum creatinine <01,0 mg/dL, then, glomerular
filtration rate (GFR) estimated must be >60 mL/min/1,73 m2 calculated from the
equation of the Modification of Diet in Renal Disease (MDRD).

9. Adequate cardiac function determined by at least one of the following:

- Left ventricular ejection fraction (LVEF) >=40% measured by echocardiography in
Multiple Gated Acquisition (MUGA) scan or isotope angiography or

- Left ventricular fractional shortening >=22% measured by echocardiography.

Exclusion Criteria:

1. Diagnosis of acute promyelocytic leukaemia (APL) in French-American-British
classification M3º or attending to the WHO classification t(15;17)(q22;q12), (PML/RAR
and variants).

2. Pre-treatment with clofarabine.

3. Previous treatment for AML or a hematological disorder AHD (excluding palliative
care, hydroxyurea, hematopoietic cytokines or lenalidomide [the latter only for a
specific AHD]). Hematopoietic cytokines and lenalidomide should not have been
administered within the 14 days preceding the first dose of study drug. If it is
received any previous treatment for AML or AHD within the time limits allowed,
drug-related toxicity, must have recovered to Grade 1 or less before the first dose
of study drug.

4. Previous hematopoietic stem cell transplantation (HSCT).

5. External beam pelvic radiotherapy.

6. Have received an investigational product within 30 days before the first dose of
study drug. If the patient has received any investigational product before this time,
the drug-related toxicity, must have recovered to Grade 1 or less before the first
dose of study drug.

7. Inadequate renal and hepatic function as follows:

- Total bilirubin >1,5 x institutional upper limit normal (ULN) provided it is not
attributable to the very LMA or

- AST y ALT >2,5 x ULN provided it is not attributable to the very LMA or

- Serum creatinine >1,0 mg/dL provided that the glomerular filtration rate (GFR)
estimated to be ≤60 mL/min/1,73 m2 calculated by the equation of the
Modification of Diet in Renal Disease (MDRD).

8. Inadequate cardiac function determined by at least one of the following:

- Left ventricular ejection fraction <40% measured by echocardiography in Multiple
Gated Acquisition (MUGA) or isotope angiography; or

- Left ventricular fractional shortening <22% measured by echocardiography.

9. Poor general condition ECOG 3-4.

10. Refusal to sign informed consent form.

11. Inability to comply with study visits and inspections.

12. Psychiatric disorders that could interfere with the consent, participation or
monitoring of the study.

13. Fungal Systemic disease, bacterial, viral or other uncontrolled infection (defined as
manifestation of signs / symptoms related to ongoing infection and without
improvement, although receiving adequate antibiotic therapy or other treatment).

14. Any other concomitant serious disease or a history of severe organ dysfunction or
heart, kidney, liver or other organ system which may involve the patient in excessive
risk when exposed to clofarabine.

15. Diagnosis of another malignancy neoplasia, unless the patient has been disease-free
for at least five years after completing an attempt curative therapy with the
following exceptions:

- Patients with non-melanoma skin cancer, carcinoma in situ or cervical
intraepithelial neoplasia, irrespective of the duration of disease-free period,
are eligible for the study if it has finalized a definitive treatment for the
disease.

- Patients with prostate cancer confined to the organ without evidence of
recurrent or progressive disease based on figures for the prostate specific
antigen (PSA) are also candidates for the study if hormonal therapy has been
initiated or has made a radical prostatectomy.

16. Clinical evidence which may indicate central nervous system (CNS) leukemia unless
lumbar puncture to confirm the absence of leukemic blasts in the cerebrospinal fluid
(CSF).

17. Previous positive test for human immunodeficiency virus (HIV).

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Efficacy

Outcome Description:

Evaluate the efficacy in terms of complete responses of induction therapy and first-line consolidation of Clofarabine and low-dose Cytarabine with AML patients aged 60 years or more. The first efficacy objective is evaluate the overall remission rate (TRG), where general reference (RG) is defined as a patient who achieved complete remission (CR) or complete remission with inadequate platelet recovery (CPR).

Outcome Time Frame:

1 year

Safety Issue:

No

Authority:

Spain: Ministry of Health

Study ID:

AML-CLOFARA-CA09

NCT ID:

NCT01193400

Start Date:

September 2010

Completion Date:

September 2013

Related Keywords:

  • Acute Myelogenous Leukemia
  • Acute myelogenous leukemia
  • Clofarabine
  • Cytarabine
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid

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