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

NCT02784561 | Unknown Phase 4 DMC

• 1 other identifier: 81370666-2
• Study Type: interventional
• Target: 80
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Leukemia

Keywords

allogeneic peripheral blood stem cell transplantation; conditioning regimen; acute leukemia; relapsed/refractory

Outcome Measures

Primary Outcomes (1)

• Number of participants relapse as assessed by NCCN (National Comprehensive Cancer Network )criteria

  two years

Secondary Outcomes (5)

• Rate of Complete Remission as assessed by NCCN (National Comprehensive Cancer Network )criteria

  30 days

• DFS(disease-free survival )

  two years

• TRM(treatment-related mortality )

  two years

• Number of participants with aGVHD as assessed by acute graft versus host disease grading criteria (refer to Glucksberg criteria)

  three months

• 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

Study Arms (1)

Busulfan/FLAG conditioning regimen

EXPERIMENTAL

All recipients in this arm received the conditioning regimen consisting of Busulfan/FLAG (fludarabine, cytarabine and granulocyte colony-stimulating factor). The conditioning regimen for peripheral blood stem cell transplantation consisted of busulfan (3.2 mg/kg/ day intravenously \[i.v.\], days -10 to -8), fludarabine (30 mg/m2, day -7 to -3), cytarabine (1.6 g/m2/day, days -7 to -3), granulocyte colony-stimulating factor (5 ug/ kg, day -8 to -3). ATG (Thymoglobuline, rabbit) for haploidentical and matched unrelated donors transplantation recipients was used on 2.5 mg/kg/d from days -5 to -2).

Drug: Busulfan (Zhejiang Otsuka Pharmaceutical Co. Ltd); Drug: Cytarabine(Actavis Italy S.p.A); Drug: Fludarabine (Bayer); Drug: granulocyte colony-stimulating factor (KirinKunpeng); Drug: rabbit ATG（Sanofi/Genzyme）

Interventions

Busulfan (Zhejiang Otsuka Pharmaceutical Co. Ltd) DRUG

busulfan (3.2 mg/kg/day intravenously \[i.v.\], days -10 to -8)

Also known as: Myleran, Busulfex

Busulfan/FLAG conditioning regimen

Cytarabine(Actavis Italy S.p.A) DRUG

cytarabine (1.6 g/m2/day, days -7 to -3)

Also known as: Ara-C

Busulfan/FLAG conditioning regimen

Fludarabine (Bayer) DRUG

fludarabine (30 mg/m2, day -7 to -3),

Also known as: fludarabine phosphate (Fludara)

Busulfan/FLAG conditioning regimen

granulocyte colony-stimulating factor (KirinKunpeng) DRUG

granulocyte colony-stimulating factor (5 ug/kg, day -8 to granulocyte recovery)

Also known as: G-CSF（granulocyte colony-stimulating factor ）

Busulfan/FLAG conditioning regimen

rabbit ATG（Sanofi/Genzyme） DRUG

ATG; thymoglobuline, rabbit;2.5 mg/kg/day, days -5 to -2

Also known as: Thymoglobuline

Busulfan/FLAG conditioning regimen

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Chinese PLA General Hospital: lead
• 309th Hospital of Chinese People's Liberation Army: collaborator
• Beijing Naval General Hospital: collaborator
• Space Center Hospital, Peking University: collaborator

Related Publications (8)

• 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.

  PMID: 23243288 BACKGROUND

• 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.

  PMID: 25881847 BACKGROUND

• Middeke JM, Herbst R, Parmentier S, Bug G, Hanel M, Stuhler G, Schafer-Eckart K, Rosler W, Klein S, Bethge W, Bitz U, Buttner B, Knoth H, Alakel N, Schaich M, Morgner A, Kramer M, Sockel K, von Bonin M, Stolzel F, Platzbecker U, Rollig C, Thiede C, Ehninger G, Bornhauser 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.

  PMID: 26283567 BACKGROUND

• 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.

  PMID: 23632950 BACKGROUND

• 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.

  PMID: 25940714 BACKGROUND

• 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; Acute Leukemia Working Party of the EBMT. 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 database. Haematologica. 2016 Aug;101(8):e352-4. doi: 10.3324/haematol.2015.140509. Epub 2016 Apr 14. No abstract available.

  PMID: 27081180 BACKGROUND

• 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.

  PMID: 27000731 BACKGROUND

• 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. doi: 10.1182/blood-2014-03-563403.

  PMID: 25082877 BACKGROUND

MeSH Terms

Conditions

Leukemia; Recurrence

Interventions

Busulfan; Cytarabine; fludarabine; fludarabine phosphate; Granulocyte Colony-Stimulating Factor; Antilymphocyte Serum

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Study Officials

• Daihong Liu, Doctor

  Chinese PLA General Hospital

  STUDY DIRECTOR

Central Study Contacts

Daihong Liu, Doctor

CONTACT

86-13681171597; daihongrm@163.com

Liping Dou, Doctor

CONTACT

86-13681207138; lipingruirui@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Hematology departemnt in Chinese PLA General Hospital

Study Record Dates

• First Submitted: May 17, 2016
• First Posted: May 27, 2016
• Study Start: July 1, 2016
• Primary Completion: July 1, 2019
• Study Completion: July 1, 2020
• Last Updated: May 27, 2016

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will not share