Clinical trial NCT04602273: Treatment of High Risk Myelodysplastic Syndromes (MDS) Not Candidates for Allogeneic Transplantation of Hematopoietic Progenitors (ALO-HSCT)
Official title: Treatment of High Risk Myelodysplastic Syndromes (MDS) Not Candidates for Allogeneic Transplantation of Hematopoietic Progenitors (ALO-HSCT)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Myelodysplastic Syndromes
Lead sponsor: Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
Sponsor class: OTHER
Collaborators: name: Hospital Son Llatzer
name: Germans Trias i Pujol Hospital
name: Celgene Corporation
First posted: 2020-10-26
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Newly diagnosed High-Risk Myelodysplastic Syndrome

Brief summary: An observational, non-interventional, prospective and multicenter study of Azacitidine in newly diagnosed High Risk Myelodysplastic Syndromes.

Primary objectives are to asses mutational status of target genes by Next Generation Sequencing, to evaluate prognostic value of geriatric assessment scales and to evaluate overall survival.

The main hypothesis is that mutation status of target genes and geriatric scales have statistical significant impact on overall survival.

Study time points will be at diagnosis, 6, 12, 18 and 24 months, always taking into account the routine clinical practice, when sample to assess mutational status will be collected. Geriatric assessment will only be performed at diagnosis.

Upon the signature of informed consent and the checking of inclusion criteria, patients will receive treatment with Azacitidine 75 mg/sqm on a 28 days based cycles (both 7-0-0 and 5-0-2 regimens are allowed) until disease progression, unacceptable toxicity or investigator decision.

150 patients are expected to be recruited at study sites.


Eligibility criteria: Inclusion Criteria:

* Patients diagnosed with myelodysplastic syndrome (MDS) according to WHO criteria, including non-proliferative chronic myelomonocytic leukemia (CMML) that is considered high risk, and not candidates for transplantation.
* High-risk MDS: (following the Grupo Español Síndrome Mielodisplásico, GESDM MDS guides) and the recommendations of Valcárcel, D. et al).

Median expected OS less than 30 months. Intermediate-2 or high risk IPSS and / or high or very high risk WPSS and / or high or very high risk IPSSS-R.

IPSS of intermediate risk and / or WPSS of intermediate risk and / or IPSS-R of intermediate risk that present at least one of the following characteristics:

Cytogenetic abnormality of the IPSS-R high or very high cytogenetic risk group Platelet count \<30 x10E9/l Neutrophil count \<0.5 x 10E9 / l Presence of dense and diffuse myelofibrosis, with or without collagen formation (grades 2-3 of the European consensus) Category 3 of the LRSS score (MD Anderson low risk score system)

* Patient diagnosed with LAM de novo according to WHO criteria, with 20-30% blasts count in bone marrow, trilineal dysplasia and more than 70 years and not candidate for intensive chemotherapy.
* Willing to provide voluntary written informed consent

Exclusion Criteria:

* Serious active medical condition, not related to MDS, that could limit patient compliance and follow-up or that, in the Investigator's opinion,could compromise the patient's safety.
* Presence of other active malignant disease
* Organic function parameters: (except when the alteration is due to MDS) Hepatic: Bilirubin\> 2 x upper limit of normal (ULN) Renal: Creatinine\> 2 x upper limit of normal (ULN)
* Ejection fraction (\<40%) and / or symptomatic heart failure.
* Leukaemia secondary to Myeloproliferative Syndrome.
* Serious psychiatric or neurological disease.
* Positive Serology for HIV.
* Proliferative CMML

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: 5- year overall survival
measure: Progression Free Survival (PFS)
timeFrame: 5-year progression free survival
measure: Overall Response Rate (OOR)
timeFrame: 12 months OOR
measure: Treatment-Emergent Adverse Events Rate (TEAE)
timeFrame: 12 Months TEAE rate
Secondary outcomes:
Other outcomes:
Locations:
city: Palma
country: Spain
facility: Son Llàtzer
state: Islas Baleares
Study officials:
affiliation: Hospital Son Llatzer
name: Joan Bargay, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Germans Trias i Pujol Hospital
name: Lurdes Zamora, PhD
role: PRINCIPAL_INVESTIGATOR
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