Study of Busulfan and FLAG Conditioning Regimen for Allogeneic Peripheral Blood Stem Cell Transplantation

Leukemia Clinical Trial

Official title:

Safety and Efficacy Study of Busulfan/FLAG Conditioning Regimen in Patients With Relapsed/Refractory Acute Leukemia Undergoing Allogeneic Peripheral Blood Stem Cell Transplantation

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02784561
• Other study ID #: 81370666-2
• Status: Not yet recruiting
• Phase: Phase 4
• First received: May 17, 2016
• Last updated: May 24, 2016
• Start date: July 2016
• Est. completion date: July 2020

Study information

• Verified date: May 2016
• Source: Chinese PLA General Hospital
• Contact: Daihong Liu, Doctor
• Phone: 86-13681171597
• Email: daihongrm[@]163.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the safety and efficacy of Busulfan/FLAG (fludarabine, cytarabine and granulocyte colony-stimulating factor) Conditioning Regimen in Patients with Relapsed/refractory Acute Leukemia undergoing allogeneic peripheral blood stem cell transplantation.

Description:

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is the only way to cure relapsed/refractory acute leukemia. Busulfan/Cyclophosphamide (BuCy, Cytarabine, Busulfan, Cyclophosphamide) has been a classical conditioning regimen for allo-SCT. Substitution of Cyclophosphamide in the BuCy regimen with Fludarabine (BuF) resulted in reduced toxicity and similar efficacy. FLAG (fludarabine, cytarabine and granulocyte colony-stimulating factor) is a chemotherapy regimen that has been proved to be effective for relapsed/refractory acute leukemia as salvage therapy. To reduce the relapse and improve the survival of those patients with relapsed/refractory acute leukemia who receive allo-SCT, the novel conditioning regimen consisting of Busulfan/FLAG was developed. The combination of Bu and FLAG without interval shortens the duration of conditioning and the pneutropenic period of the patient compared with successive administration of FLAG followed with BuF. In addition, regarding the established safety and efficacy of BuF and FLAG, it is reasonable to expect similar safety and enhanced antileukemic efficacy for Bu/FLAG compared with BuF. In this study, the safety and efficacy of this regimen in patients with relapsed/refractory acute leukemia undergoing allogeneic peripheral blood stem cell transplantation was investigated.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: July 2020
• Est. primary completion date: July 2019
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years to 65 Years

Eligibility

Inclusion Criteria:

• relapsed/refractory acute leukemia regardless of cytogenetics

• All patients should aged 12 to 65 years

• Have matched sibling donors, =8/10 HLA(human leukocyte antigen) matched unrelated donors or haploidentical donors

• Patients without any uncontrolled infections or without severe pulmonary, renal, hepatic or cardiac diseases

Exclusion Criteria:

• Patients aged less than 12 years old

• Patients with any uncontrolled infections or with severe pulmonary, renal, hepatic or cardiac diseases

• Acute myeloid leukemia patients with t (15;17)

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia

Intervention

Drug:
• Busulfan (Zhejiang Otsuka Pharmaceutical Co. Ltd)
busulfan (3.2 mg/kg/day intravenously [i.v.], days -10 to -8)
• Cytarabine(Actavis Italy S.p.A)
cytarabine (1.6 g/m2/day, days -7 to -3)
• Fludarabine (Bayer)
fludarabine (30 mg/m2, day -7 to -3),
• granulocyte colony-stimulating factor (KirinKunpeng)
granulocyte colony-stimulating factor (5 ug/kg, day -8 to granulocyte recovery)
• rabbit ATG(Sanofi/Genzyme)
ATG; thymoglobuline, rabbit;2.5 mg/kg/day, days -5 to -2

Locations

Country	Name	City	State
n/a

Sponsors (4)

Lead Sponsor	Collaborator
Chinese PLA General Hospital	309th Hospital of Chinese People's Liberation Army, Beijing Naval General Hospital, Space Center Hospital, Peking University

References & Publications (8)

Chang YJ, Huang XJ. Haploidentical stem cell transplantation: anti-thymocyte globulin-based experience. Semin Hematol. 2016 Apr;53(2):82-9. doi: 10.1053/j.seminhematol.2016.01.004. Epub 2016 Jan 18. Review. — View Citation

Forman SJ, Rowe JM. The myth of the second remission of acute leukemia in the adult. Blood. 2013 Feb 14;121(7):1077-82. doi: 10.1182/blood-2012-08-234492. Epub 2012 Dec 14. Review. — View Citation

Fu H, Xu L, Liu D, Zhang X, Liu K, Chen H, Wang Y, Han W, Han T, Huang X. Late-onset hemorrhagic cystitis after haploidentical hematopoietic stem cell transplantation in patients with advanced leukemia: differences in ATG dosage are key. Int J Hematol. 2013 Jul;98(1):89-95. doi: 10.1007/s12185-013-1350-8. Epub 2013 Apr 30. — View Citation

Middeke JM, Herbst R, Parmentier S, Bug G, Hänel M, Stuhler G, Schäfer-Eckart K, Rösler W, Klein S, Bethge W, Bitz U, Büttner B, Knoth H, Alakel N, Schaich M, Morgner A, Kramer M, Sockel K, von Bonin M, Stölzel F, Platzbecker U, Röllig C, Thiede C, Ehninger G, Bornhäuser M, Schetelig J. Clofarabine salvage therapy before allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory AML: results of the BRIDGE trial. Leukemia. 2016 Feb;30(2):261-7. doi: 10.1038/leu.2015.226. Epub 2015 Aug 18. — View Citation

Sun Y, Beohou E, Labopin M, Volin L, Milpied N, Yakoub-Agha I, Piemontese S, Polge E, Houhou M, Huang XJ, Mohty M, Nagler A, Gorin NC. Unmanipulated haploidentical versus matched unrelated donor allogeneic stem cell transplantation in adult patients with acute myelogenous leukemia in first remission: A retrospective pair-matched comparative study of the Beijing approach with the EBMT data base. Haematologica. 2016 Apr 14. pii: haematol.2015.140509. [Epub ahead of print] — View Citation

Tang W, Fan X, Wang L, Hu J. Busulfan and fludarabine conditioning regimen given at hematological nadir of cytoreduction fludarabine, cytarabine, and idarubicin chemotherapy in patients with refractory acute myeloid leukemia undergoing allogeneic stem cell transplantation: a single arm pilot consort study. Medicine (Baltimore). 2015 Apr;94(15):e706. doi: 10.1097/MD.0000000000000706. — View Citation

Wang Y, Liu QF, Xu LP, Liu KY, Zhang XH, Ma X, Fan ZP, Wu DP, Huang XJ. Haploidentical vs identical-sibling transplant for AML in remission: a multicenter, prospective study. Blood. 2015 Jun 18;125(25):3956-62. doi: 10.1182/blood-2015-02-627786. Epub 2015 May 4. — View Citation

Wang Y, Wu DP, Liu QF, Qin YZ, Wang JB, Xu LP, Liu YR, Zhu HH, Chen J, Dai M, Huang XJ. In adults with t(8;21)AML, posttransplant RUNX1/RUNX1T1-based MRD monitoring, rather than c-KIT mutations, allows further risk stratification. Blood. 2014 Sep 18;124(12):1880-6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants relapse as assessed by NCCN (National Comprehensive Cancer Network )criteria		two years	No
Secondary	Rate of Complete Remission as assessed by NCCN (National Comprehensive Cancer Network )criteria		30 days	No
Secondary	DFS(disease-free survival )		two years	No
Secondary	TRM(treatment-related mortality )		two years	Yes
Secondary	Number of participants with aGVHD as assessed by acute graft versus host disease grading criteria (refer to Glucksberg criteria)		three months	No
Secondary	Number of participants with Regimen-related adverse events as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03		30 days	No