Clinical trial NCT03339700: Addition of Gemcitabine to Pre Allo-HSCT Conditioning for Acute Lymphoblastic Leukemia
Official title: Addition of Gemcitabine to the Standard Reduced Busulfan and Cyclophosphamide (BUCY2) Pre Allogeneic Hematopoietic Stem Cell Transplantation Conditioning for Acute Lymphoblastic Leukemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Acute Lymphoblastic Leukemia, Adult
Lead sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Sponsor class: OTHER
First posted: 2017-11-13
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The main purpose of the project is to evaluate the disease free survival and overall survival in patients diagnosed with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) adding gemcitabine to the standard institutional conditioning regimen based on two alkylating drugs, reduced busulfan and cyclophosphamide (reduced BUCY 2).

Detailed description: In the last decade, hematopoietic stem cell transplantation (HSCT) has become an efficient strategy for the treatment of high risk acute lymphoblastic leukemias. Lymphoid acute leukemias (ALL) are considered malignant clonal diseases of the hematopoietic stem cells, and represent a therapeutic challenge due to the high relapse rate and mortality using conventional chemotherapy regimens. Many studies have shown a decrease in relapse and an increase in overall survival with allogeneic HSCT, however, despite the fact that results in ALL have improved in the past years, achieving complete remission (CR) in approximately 75% of the patients, the relapse rate remains high and long term survival is lower than 50% depending on age and disease characteristics. On the other hand, it has been stated that relapse is higher when an allo-HSCT is performed in second CR, obtaining poorer results compared to performing HSCT in first CR, although better than chemotherapy alone (87% probability of relapse).

It is necessary to implement strategies that increase efficiency of pre transplant conditioning regimens in patients diagnosed with ALL undergoing an allo-HSCT in order to reduce relapse and increase overall survival. The hypothesis is that adding gemcitabine to the standard institutional conditioning regimen (reduced BUCY 2) in patients with ALL undergoing an allo-HSCT, the relapse free survival as well as the overall survival will improve, because it has been demonstrated in other malignant hematological diseases that gemcitabine plus two alkylating agents, facilitates synergism with busulfan and melphalan, inhibiting the DNA damage repair and causing a higher cytotoxic effect.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of acute lymphoblastic leukemia in 2nd complete remission or primary refractory disease, candidates to hematopoietic stem cell transplantation.
* Hemoglobin ≥ 10 g/dl, Absolute Neutrophil Count ≥ 1 x 103/mm3, and Platelets ≥ 100,000 /µL
* Eastern Cooperative Oncology Group status (ECOG) ≤2 oR Karnofsky ≥80%
* Signed Informed Consent
* Left ventricular ejection fraction (LVEF) \>40%
* Normal liver function enzyme tests
* Preserved renal function

Exclusion Criteria:

* Patients not willing to participate or to sign the informed consent
* Patients who do not meet the inclusion criteria

Primary outcomes:
measure: Disease Free Survival
timeFrame: 3 years
Secondary outcomes:
measure: Overall Survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
state: Distrito Federal
Study officials:
affiliation: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
name: Eucario Leon Rodriguez, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
name: Monica M Rivera Franco, M.D.,MSc
role: PRINCIPAL_INVESTIGATOR
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