Clinical trial NCT03023384: Feasibility Study of Intermediate Doses of ARA-C With Autologous SCT as Consolidation of Low/Intermediate-risk AML
Official title: Feasibility Study of the Use of Intermediate Doses of Cytarabine Associated With Autologous Hematopoietic Stem Cells as Consolidation Treatment of Young Adults With Low- or Intermediate-risk de Novo Acute Myeloid Leukemia
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Acute Myeloid Leukemia
Keywords: Acute Myeloid Leukemia
Chemotherapy
Autologous Stem Cell Transplantation
Developing country
Clinical network
Lead sponsor: International Consortium on Acute Leukemias
Sponsor class: OTHER
First posted: 2017-01-18
Enrollment: 547
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Adult patients with Acute Myeloid Leukemia

Brief summary: Create a network of institutions in developing countries that will perform AML diagnosis, risk classification, treatment, supportive care and follow-up evaluation according to a common protocol and will register data using common clinical research forms (CRFs) in a single database and available on the internet.

Detailed description: 1. Compare overall survival and disease-free survival of patients with acute myeloid leukemia classified according the European LeukemiaNet treated in participating South American hospitals with the results reported in developed countries.
2. Compare overall survival and disease-free survival of patients with AML low or intermediate risk treated with two cycles of cytarabine in intermediate dose versus one cytarabine cycle at the same dose followed by autologous SCT as consolidation. The risk will be established according to the classification of the European LeukemiaNet.
3. Create a network of institutions in developing countries that will perform AML diagnosis, risk classification, treatment, supportive care and follow-up evaluation according to a common protocol and will register data using common clinical research forms (CRFs) in a single database and available on the internet
4. Using National Reference Laboratories, provide cytogenetic and molecular methods for all institutions participating in the network, thus allowing rapid diagnosis and risk stratification of AML cases according to the European LeukemiaNet structure;
5. Develop a method of assessing minimal residual disease based on flow cytometry adapted to local resources and capable of guiding therapeutic decisions;
6. Determine the time interval between: a) diagnosis and risk group determination; b) the first cycle of consolidation chemotherapy and autologous hematopoietic stem cells infusion;
7. Determine the frequency and etiologic agent of infections associated with treatment, the number and average duration of hospitalization due to episodes of neutropenia;
8. Create a bank of samples of bone marrow from AML patients at different times of treatment;
9. Determine the disease-free survival and the cumulative incidence rate of relapse and non-relapse mortality and compare them between chemotherapy alone and chemotherapy plus autologous SCT cohorts.

Eligibility criteria: Inclusion Criteria:

1. Acute myeloid leukemia (AML) diagnosis according to WHO criteria;
2. AML not treated previously, including: de novo AML or secondary to myelodysplastic syndromes;
3. Absence of t(15;17), or PML-RARA rearrangement and its variants (acute promyelocytic leukemia diagnosis);
4. Age greater than or equal to 18 years old or lower than or equal to 65 years old;
5. Functional status ECOG from 0 to 2;
6. Signed informed consent;
7. Ability to follow the protocol procedures;
8. Willingness to use birth control methods during the treatment until its conclusion;
9. Adequate renal and liver function:

   * Bilirubin ≤ 1.5x the upper limit of normality;
   * AST and ALT ≤ 2.5x the upper limit of normality;
   * Creatinine ≤ 2.5 mg/dL.
10. Suitable cardiac function: left ventricular ejection fraction ≥ 50%.

Exclusion Criteria:

1. Acute promyelocytic leukemia (APL) diagnosis according to WHO criteria;
2. Diagnosis of acute leukemia of ambiguous lineage, biphenotypic acute leukemia or undifferentiated acute leukemia, according to WHO criteria;
3. AML previously treated, except with hydroxyurea administration for cytoreduction;
4. Age greater than 65 years old or lower than 18 years old;
5. Functional status ECOG greater than 2;
6. Do not sign the informed consent;
7. Inability to follow the protocol procedures;
8. Be fertile female who are unwilling to take any birth control method during the treatment;
9. Hypersensitivity to any drug of the treatment protocol;
10. Positive serology for HIV;
11. Altered liver and renal function not related to the primary disease (AML):

    * Bilirubin \> 1.5x the upper limit of normality
    * AST and ALT \> the 2.5x upper limit of normality
    * Creatinine \> 2.5 mg/dL

n) Altered cardiac function, with LVEF \<50%

Primary outcomes:
measure: Disease free survival
timeFrame: 2 years
Secondary outcomes:
measure: Overall survival
timeFrame: 2 years
Other outcomes:
Locations:
city: Porto Alegre
country: Brazil
facility: Hospital das Clinicas de Porto Alegre
state: Rio Grande do Sul
city: Campinas
country: Brazil
facility: Hospital das Clínicas da Unicamp
state: São Paulo
city: Ribeirao Preto
country: Brazil
facility: Hospital das Clinicas de Ribeirão Preto
state: São Paulo
city: Santo Andre
country: Brazil
facility: Hospital Mario Covas
state: São Paulo
city: Sao Jose do Rio Preto
country: Brazil
facility: Hospital de Base de São José do Rio Preto
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Hospital São Paulo
state: São Paulo
Study officials:
affiliation: University of Sao Paulo
name: Eduardo M Rego, MD
role: PRINCIPAL_INVESTIGATOR
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