Addition of Gemcitabine to Pre Allo-HSCT Conditioning for Acute Lymphoblastic Leukemia

NCT ID: NCT03339700

Last Updated: 2020-01-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-09-15

Study Completion Date

2021-09-30

Brief Summary

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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).

Detailed Description

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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.

Conditions

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Acute Lymphoblastic Leukemia, Adult

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Unique

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.

Group Type EXPERIMENTAL

Gemcitabine

Intervention Type DRUG

4800mg/m2, intravenous (IV), divided 4 days, 1200mg/m2/day, during days -5 to -2

Busulfan

Intervention Type DRUG

12mg/kg, Oral, divided in 4 days, 3mg/kg/day Oral, during days -7 to -4.

Cyclophosphamide

Intervention Type DRUG

80mg/kg, intravenous (IV), divided in 2 days, 40mg/kg/day IV, during days -3 and -2.

Allogeneic Hematopoietic Stem Cell Transplantation

Intervention Type PROCEDURE

Bone Marrow HSC (allogeneic HSCT) transfusion, day 0

Interventions

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Gemcitabine

4800mg/m2, intravenous (IV), divided 4 days, 1200mg/m2/day, during days -5 to -2

Intervention Type DRUG

Busulfan

12mg/kg, Oral, divided in 4 days, 3mg/kg/day Oral, during days -7 to -4.

Intervention Type DRUG

Cyclophosphamide

80mg/kg, intravenous (IV), divided in 2 days, 40mg/kg/day IV, during days -3 and -2.

Intervention Type DRUG

Allogeneic Hematopoietic Stem Cell Transplantation

Bone Marrow HSC (allogeneic HSCT) transfusion, day 0

Intervention Type PROCEDURE

Other Intervention Names

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Gemzar Myleran Cytoxan Allogeneic Bone Marrow Transplantation

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Eucario Leon Rodriguez, M.D.

Role: PRINCIPAL_INVESTIGATOR

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Monica M Rivera Franco, M.D.,MSc

Role: PRINCIPAL_INVESTIGATOR

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Locations

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Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Mexico City, Mexico City, Mexico

Site Status RECRUITING

Countries

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Mexico

Central Contacts

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Eucario Leon Rodriguez, M.D.

Role: CONTACT

525554870900 ext. 2255

Monica M Rivera Franco, M.D.,MSc

Role: CONTACT

525554870900 ext. 2719

Facility Contacts

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Eucario Leon Rodriguez, M.D.

Role: primary

525554870900 ext. 2255

Monica M Rivera Franco, M.D.

Role: backup

525554870900 ext. 2719

References

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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.

Reference Type BACKGROUND
PMID: 22643322 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8893877 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24816580 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21859247 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14965358 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7718326 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7481844 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7481845 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8893876 (View on PubMed)

Other Identifiers

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INCMNSZ REF 2235

Identifier Type: -

Identifier Source: org_study_id

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