A Phase III Randomized, Double-Blind, Controlled Study Comparing Clofarabine and Cytarabine versus Cytarabine Alone in Adult Patients 55 Years and Older with Acute Myelogenous Leukemia (AML) who have Relapsed or are Refractory after Receiving up to Two Prior Induction Regimens - CLASSIC I

• Register: EUCTR
• Last refreshed on: 10 July 2012
• Main ID: EUCTR2008-001043-19-IT
• Date of registration: 09/02/2009
• Prospective Registration: No
• Primary sponsor: Genzyme Europe BV
• Public title: A Phase III Randomized, Double-Blind, Controlled Study Comparing Clofarabine and Cytarabine versus Cytarabine Alone in Adult Patients 55 Years and Older with Acute Myelogenous Leukemia (AML) who have Relapsed or are Refractory after Receiving up to Two Prior Induction Regimens - CLASSIC I
• Scientific title: A Phase III Randomized, Double-Blind, Controlled Study Comparing Clofarabine and Cytarabine versus Cytarabine Alone in Adult Patients 55 Years and Older with Acute Myelogenous Leukemia (AML) who have Relapsed or are Refractory after Receiving up to Two Prior Induction Regimens - CLASSIC I
• Date of first enrolment: 30/12/2008
• Target sample size: 376
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-001043-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

France, Germany, Italy

Key inclusion & exclusion criteria

Inclusion criteria:
1. Provide signed, written informed consent.
2. Have a diagnosis of AML according to the WHO classification (see appendix B of study protocol
3. Have received not more than two prior induction regimens for treatment of AML according to the following definitions and qualifications:
- Induction regimen: a drug or combination of drugs administered for a pre-specified number of cycles (usually not exceeding 2 cycles total) to patients with AML with the intent of achieving a CR or CRi;
- At least 1 prior induction regimen must have included cytotoxic chemotherapy;
- Hematopoietic stem cell transplantation (HSCT) (administered after induction therapy) is not considered a distinct induction regimen.
- Consolidation or maintenance regimens (administered after CR or CRi documented) are not considered distinct induction regimens.
4. Are refractory or relapsed (requiring at least 5% leukemic blasts in the bone marrow, regardless of the presence of other features such as new or recurrent dysplastic changes or extramedullary disease)
5. Be 55 years of age or older at the time of signing the informed consent.
6. Have an ECOG performance status score of 0, 1, or 2.
7. Be able to comply with study procedures and follow-up examinations.
8. Be nonfertile or agree to use birth control (ie, condom, diaphragm, cervical cap, etc) during the study and for at least 90 days after the last dose of study drug.
9. Have adequate renal and hepatic function as indicated by the following laboratory values : Renal-Estimated GFR >=60 mL/min/1.73m2 , Hepatic Serum bilirubin <=1.5 x ULN, AST and ALT <=2.5 x ULN, Alkaline phosphatase <=2.5 x ULN.
GFR= Glomerular filtration rate, estimated by the Modification of Diet in Renal Disease (MDRD) equation.
ULN = Istituition Upper Limit of Normal
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Received previous treatment with clofarabine.
2. Received intermediate- or high-dose cytarabine (IDAC or HDAC, respectively) defined as a bolus administration schedule at >= 500 mg/m2/dose as a component of prior induction or consolidation therapy.
3. Have received an HSCT within the previous 3 months prior to study entry.
4. Have >= grade 2 acute GVHD. (added Italian definition GVHD (Graft Versus Host Disease)
5. Have either moderate or severe chronic GvHD, whether limited or extensive chronic GvHD. Patients with mild limited or extensive chronic GvHD may be included.
6. Are receiving any other antileukemic therapy (standard or investigational). Patients must not have received previous therapy for at least 2 weeks prior to the first dose of study drug and must have recovered from any prior drug-related non-hematologic toxicity to &#61603; grade 2, with the following exceptions:
- hydroxyurea, which must not have been received <24 hours prior to the first dose of study drug.
- monoclonal antibodies, which must not have been received for 6 weeks prior to the first dose of study drug.
7. Have psychiatric disorders that would interfere with consent, study participation, or follow-up.
8. Have a systemic fungal, bacterial, viral, or other infection not controlled
9. Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo induction therapy with either or both of these agents.
10. Have been diagnosed with another malignancy, unless the patient has been disease free for at least 5 years following curative intent therapy.
11. Have clinical evidence suggestive of CNS involvement with leukemia unless a lumbar puncture confirms the absence of leukemic blasts in the CSF.
12. Known HIV positivity.
13. Are pregnant or lactating.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Acute Myelogenous Leukemia (AML)
MedDRA version: 9.1 Level: LLT Classification code 10059034
MedDRA version: 9.1 Level: LLT Classification code 10000889

Intervention(s)

Trade Name: EVOLTRA
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Clofarabine
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Pharmaceutical Form: Powder for infusion*
INN or Proposed INN: Cytarabine
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Primary Outcome(s)

Main Objective: To assess the efficacy of clofarabine in combination with cytarabine compared with cytarabine alone in adult patients 55 years and older with AML who have either relapsed or are refractory after receiving up to two prior induction regimens, as measured by overall survival (OS).

Primary end point(s): Overall survival

Secondary Objective: To determine the overall remission (OR) rate (CR + CRi) (added Italian definition: CR (morphologic Competed Remission) + CRi (with morphologic Completed Remission with incomplete peripheral blood count recovery)) of clofarabine in combination with cytarabine compared with cytarabine alone.
To determine the duration of remission and disease free survival for each treatment group.
To compare treatment groups with respect to event free survival (EFS) and 4 month event-free survival.
To determine the safety and tolerability of clofarabine when used in combination with cytarabine compared with cytarabine alone and the duration, seriousness, and relationship of adverse events which occur during the treatment and follow-up, including hospitalizations.

Secondary ID(s)

2008-001043-19-DE

CLO34100405