Clofarabine and Low-dose Cytarabine Followed by Consolidation Therapy in AML Patients Age Greater Than or Equal to 60 Years

NCT01193400 | Terminated Phase 2 DMC

• 2 other identifiers: AML-CLOFARA-CA092010-019718-25
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 15

Brief Summary

Primary outcome measure: 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). Secondary outcome measures:

• To evaluate disease-free survival (DFS)
• Evaluate the overall survival (OS)
• To evaluate the safety and tolerability of clofarabine and duration, severity and relationship of adverse events (AEs) occurring during treatment
• To assess the rate of mortality at 30 days (ie, the incidence of deaths occurring between Day 1 and Day 30 of induction cycle)
• The incidence, intensity (according to the latest version of the CTCAE classification), duration, causality, severity and type of AA

Conditions

Acute Myelogenous Leukemia

Keywords

Acute myelogenous leukemia; Clofarabine; Cytarabine

Outcome Measures

Primary Outcomes (1)

• Efficacy

  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).

  1 year

Secondary Outcomes (5)

• To evaluate disease-free survival (DFS)

• Evaluate the overall survival (OS)

• To evaluate the safety

• To assess the rate of mortality at 30 days

• • The incidence, intensity (according to the latest version of the CTCAE classification), duration, causality, severity and type of AE

Study Arms (1)

Clofarabine-Cytarabine

EXPERIMENTAL

Induction therapy with a combination of clofarabine and low-dose cytarabine followed by consolidation therapy with clofarabine and low-dose cytarabine

Drug: Clofarabine; Drug: Cytarabine

Interventions

Clofarabine DRUG

Clofarabine-Cytarabine

Cytarabine DRUG

Clofarabine-Cytarabine

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of AML (de novo, secondary, or hematological disorder), according to WHO criteria.
• Older than or equal to 60 years
• ECOG performance status 0-2
• 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
• Provide written informed consent form.
• Being able to comply with study procedures and follow-up evaluations.
• 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.
• 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

You may not qualify if:

• 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).
• Pre-treatment with clofarabine.
• 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.
• Previous hematopoietic stem cell transplantation (HSCT).
• External beam pelvic radiotherapy.
• 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.
• 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).
• 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.
• Poor general condition ECOG 3-4.
• Refusal to sign informed consent form.

Sponsors & Collaborators

• PETHEMA Foundation: lead
• Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias: collaborator

Study Sites (15)

Hospital Juan Canalejo.

A Coruña, Spain

Location

Hospital General de Alicante.

Alicante, Spain

Location

Hospital de la Santa Creu i Sant Pau.

Barcelona, Spain

Location

Hospital Durán i Reynals (Bellvitge).

Barcelona, Spain

Location

Hospital Vall d' Hebron

Barcelona, Spain

Location

ICO Hospital Germans Trias I Pujol.

Barcelona, Spain

Location

Hospital Reina Sofía.

Córdoba, Spain

Location

Hospital 12 de Octubre.

Madrid, Spain

Location

Hospital Ramón y Cajal.

Madrid, Spain

Location

Hospital San Pedro de Alcántara.

Málaga, Spain

Location

Hospital Central de Asturias.

Oviedo, Spain

Location

Hospital Clínico Universitario de Salamanca.

Salamanca, Spain

Location

Hospital Virgen del Rocío

Seville, Spain

Location

Hospital Clínico de Valencia.

Valencia, Spain

Location

Hospital Universitario La Fe.

Valencia, Spain

Location

Related Publications (1)

• Martinez-Cuadron D, Montesinos P, Oriol A, Salamero O, Vidriales B, Bergua J, Herrera P, Vives S, Sanz J, Carpio C, Rodriguez-Veiga R, Moscardo F, Sanz MA. Phase II trial to assess the safety and efficacy of clofarabine in combination with low-dose cytarabine in elderly patients with acute myeloid leukemia. Ann Hematol. 2014 Jan;93(1):43-6. doi: 10.1007/s00277-013-1914-y. Epub 2013 Oct 1.

  PMID: 24081577 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Clofarabine; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 31, 2010
• First Posted: September 1, 2010
• Study Start: September 1, 2010
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: April 7, 2014

Record last verified: 2014-04

Locations

ES (15)