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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Unique | Experimental | Patients will receive reduced Busulfan and Cyclophosphamide (BUCY 2) conditioning regimen, consisting in the administration of two medications: Busulfan and Cyclophosphamide Plus: Gemcitabine. Then patients will undergo an Allogeneic Hematopoietic Stem Cell Transplantation. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Gemcitabine | Drug | 4800mg/m2, intravenous (IV), divided 4 days, 1200mg/m2/day, during days -5 to -2 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Disease Free Survival | Time between transplantation and relapse or last follow-up | 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival | Time between transplantation and dead or last follow-up | 5 years |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Eucario Leon Rodriguez, M.D. | Contact | 525554870900 | 2255 | eucarios@hotmail.com |
| Monica M Rivera Franco, M.D.,MSc | Contact | 525554870900 | 2719 | monrif90d@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Eucario Leon Rodriguez, M.D. | Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran | Principal Investigator |
| Monica M Rivera Franco, M.D.,MSc | Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran | Recruiting | Mexico City | Mexico City | 14080 | Mexico |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22643322 | Background | Nieto Y, Thall P, Valdez B, Andersson B, Popat U, Anderlini P, Shpall EJ, Bassett R, Alousi A, Hosing C, Kebriaei P, Qazilbash M, Frazier E, Gulbis A, Chancoco C, Bashir Q, Ciurea S, Khouri I, Parmar S, Shah N, Worth L, Rondon G, Champlin R, Jones RB. High-dose infusional gemcitabine combined with busulfan and melphalan with autologous stem-cell transplantation in patients with refractory lymphoid malignancies. Biol Blood Marrow Transplant. 2012 Nov;18(11):1677-86. doi: 10.1016/j.bbmt.2012.05.011. Epub 2012 May 27. | |
| 8893877 |
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| Busulfan | Drug | 12mg/kg, Oral, divided in 4 days, 3mg/kg/day Oral, during days -7 to -4. |
|
|
| Cyclophosphamide | Drug | 80mg/kg, intravenous (IV), divided in 2 days, 40mg/kg/day IV, during days -3 and -2. |
|
|
| Allogeneic Hematopoietic Stem Cell Transplantation | Procedure | Bone Marrow HSC (allogeneic HSCT) transfusion, day 0 |
|
|
| Background |
| Peters GJ, Ruiz van Haperen VW, Bergman AM, Veerman G, Smitskamp-Wilms E, van Moorsel CJ, Kuiper CM, Braakhuis BJ. Preclinical combination therapy with gemcitabine and mechanisms of resistance. Semin Oncol. 1996 Oct;23(5 Suppl 10):16-24. |
| 24816580 | Background | Wang E, Gulbis A, Hart JW, Nieto Y. The emerging role of gemcitabine in conditioning regimens for hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2014 Sep;20(9):1382-9. doi: 10.1016/j.bbmt.2014.04.025. Epub 2014 May 9. |
| 21859247 | Background | Anderlini P, Saliba RM, Ledesma C, Chancoco C, Alousi AM, Shpall EJ, Popat UR, Hosing CM, Khouri IF, Nieto Y, Ciurea S, Younes A, Fanale MA, Acholonu S, Valverde R, Champlin RE. Gemcitabine, fludarabine and melphalan as a reduced-intensity conditioning regimen for allogeneic stem cell transplant in relapsed and refractory Hodgkin lymphoma: preliminary results. Leuk Lymphoma. 2012 Mar;53(3):499-502. doi: 10.3109/10428194.2011.615427. Epub 2011 Oct 24. No abstract available. |
| 14965358 | Background | Matsuda A, Sasaki T. Antitumor activity of sugar-modified cytosine nucleosides. Cancer Sci. 2004 Feb;95(2):105-11. doi: 10.1111/j.1349-7006.2004.tb03189.x. |
| 7718326 | Background | Spasokoukotskaja T, Arner ES, Brosjo O, Gunven P, Juliusson G, Liliemark J, Eriksson S. Expression of deoxycytidine kinase and phosphorylation of 2-chlorodeoxyadenosine in human normal and tumour cells and tissues. Eur J Cancer. 1995;31A(2):202-8. doi: 10.1016/0959-8049(94)00435-8. |
| 7481844 | Background | Braakhuis BJ, Ruiz van Haperen VW, Boven E, Veerman G, Peters GJ. Schedule-dependent antitumor effect of gemcitabine in in vivo model system. Semin Oncol. 1995 Aug;22(4 Suppl 11):42-6. |
| 7481845 | Background | Csoka K, Liliemark J, Larsson R, Nygren P. Evaluation of the cytotoxic activity of gemcitabine in primary cultures of tumor cells from patients with hematologic or solid tumors. Semin Oncol. 1995 Aug;22(4 Suppl 11):47-53. |
| 8893876 | Background | Plunkett W, Huang P, Searcy CE, Gandhi V. Gemcitabine: preclinical pharmacology and mechanisms of action. Semin Oncol. 1996 Oct;23(5 Suppl 10):3-15. |
| ID | Term |
|---|---|
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| ID | Term |
|---|---|
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D000093542 | Gemcitabine |
| D002066 | Busulfan |
| D003520 | Cyclophosphamide |
| ID | Term |
|---|---|
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D002072 | Butylene Glycols |
| D006018 | Glycols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D008698 | Mesylates |
| D000476 | Alkanesulfonates |
| D017738 | Alkanesulfonic Acids |
| D000473 | Alkanes |
| D006839 | Hydrocarbons, Acyclic |
| D006838 | Hydrocarbons |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| D013457 | Sulfur Compounds |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
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