CBA Versus FBA Conditioning Followed by Allogeneic HSCT in Treatment of High Risk and Refractory AML

NCT03384212 | Unknown Phase 3 DMC

• 1 other identifier: 2016-22
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Aim: To evaluated if cladribine based conditioning (CBA) could decrease relapse after HLA matched HSCT in high risk and refractory AML patients as compared with fludarabine based conditioning regimen(FBA). Study design: open-labed, prospective, multicenter, randomized control study Number of subjects: 60 each group Treatment: CBA group: CBA as HSCT conditioning which including cladribine 5mg/m2 day -6 to day -2 , busulfan(iv) 3.2mg/kg day-6 to day -3 and cytarabine 2g/m2 day-6 to day -2. FBA group: FBA as HSCT conditioning which including fludarabine 30mg/m2 day -6 to day -2, busulfan(iv) 3.2mg/kg day-6 to day -3 and cytarabine 2g/m2 day-6 to day -2.

Conditions

High Risk Acute Myeloid Leukemia; Allogeneic Hematopoeitic Stem Cell Transplantation

Keywords

cladribine; fludarabine; relapse

Outcome Measures

Primary Outcomes (1)

• cumulative relapse rate at 2 year

  The percentage of all patients who are relapsed within 2 years after allogeneic HSCT.

  2 years

Secondary Outcomes (4)

• overall survival at 2 year

  2 years

• disease free survival at 2year

  2 years

• non-relapse mortality at 2year

  2 years

• non-relapse mortality at 100days

  100 days

Study Arms (2)

CBA group

EXPERIMENTAL

CBA as HSCT conditioning: cladribine 5mg/m2 day -6 to day -2 busulfan(iv) 3.2mg/kg day-6 to day -3 cytarabine 2g/m2 day-6 to day -2

Drug: Cladribine; Drug: Busulfan; Drug: Cytarabine

FBA group

ACTIVE COMPARATOR

FBA as HSCT conditioning: fludarabine 30mg/m2 day -6 to day -2 busulfan(iv) 3.2mg/kg day-6 to day -3 cytarabine 2g/m2 day-6 to day -2

Drug: Fludarabine; Drug: Busulfan; Drug: Cytarabine

Interventions

Cladribine DRUG

Also known as: chlorodeoxyadenosine

CBA group

Fludarabine DRUG

FBA group

Busulfan DRUG

Also known as: busulphan

CBA group; FBA group

Cytarabine DRUG

Also known as: cytosine arabinoside

CBA group; FBA group

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis of AML confirmed by bone marrow cell morphology, immunology, cytogenetics and molecular biology (MICM). Blast crisis of chronic myeloid leukemia (CML) and AML transferred from myelodysplastic syndrome(MDS) or other diseases are also included.
• AML with high risk cytogenetic abnormals, such as FLT3- ITD, et al.
• Patients fulfilled at least one of the following criteria defining refractory AML:(1) primary induction failure (PIF) after 2 or more cycles of chemotherapy; (2) first early relapse after a remission duration of fewer than 12 months and refractory to salvage combination chemotherapy; (3) second or subsequent relapse .
• Have HLA 9/10 or 10/10 matched siblings or unrelated donor，the donor must match the health conditions of hematopoietic stem cell donation (criteria of China Marrow Donor Program) and be willing to donate.
• Performance status score no more than 2 (ECOG criteria).
• Adequate organ function as defined by the following criteria:ALT, AST and total serum bilirubin \<2×ULN (upper limit of normal), Serum creatinine and BUN \<1.25×ULN.
• Adequate cardiac function without acute myocardial infarction, arrhythmia or atrioventricular block, heart failure, active rheumatic heart disease and cardiac dilatation.
• Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment.
• Willingness and ability to comly with scheduled visits, treatment plans, laboratory tests, and other study procedures.

You may not qualify if:

• Presence of any condition inappropriate for HSCT.
• Presence of any fatal disease, including respiratory failure, heart failure, liver or kidney function failure et al.
• Have no suitable donor.
• Pregnancy or breast feeding.
• Current treatment on another clinical trail.
• Any other condition the investigator judged the patient inappropriate for entry into this study.

Sponsors & Collaborators

• Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine: lead
• Changhai Hospital: collaborator
• Xiangya Hospital of Central South University: collaborator
• Tongji Hospital: collaborator
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: collaborator
• Chengdu PLA General Hospital: collaborator
• Tang-Du Hospital: collaborator
• Fujian Medical University Union Hospital: collaborator

Study Sites (1)

Shanghai general hospital, Shanghai Jiaotong university school of medicine

Shanghai, Shanghai Municipality, 200080, China

RECRUITING

Related Publications (2)

• Holowiecki J, Grosicki S, Robak T, Kyrcz-Krzemien S, Giebel S, Hellmann A, Skotnicki A, Jedrzejczak WW, Konopka L, Kuliczkowski K, Zdziarska B, Dmoszynska A, Marianska B, Pluta A, Zawilska K, Komarnicki M, Kloczko J, Sulek K, Haus O, Stella-Holowiecka B, Baran W, Jakubas B, Paluszewska M, Wierzbowska A, Kielbinski M, Jagoda K; Polish Adult Leukemia Group (PALG). Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia. Multicenter, phase III study. Leukemia. 2004 May;18(5):989-97. doi: 10.1038/sj.leu.2403336.

  PMID: 14999298 BACKGROUND

• Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, Skotnicki AB, Hellmann A, Sulek K, Dmoszynska A, Kloczko J, Jedrzejczak WW, Zdziarska B, Warzocha K, Zawilska K, Komarnicki M, Kielbinski M, Piatkowska-Jakubas B, Wierzbowska A, Wach M, Haus O. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. J Clin Oncol. 2012 Jul 10;30(20):2441-8. doi: 10.1200/JCO.2011.37.1286. Epub 2012 Apr 16.

  PMID: 22508825 BACKGROUND

MeSH Terms

Conditions

Recurrence

Interventions

Cladribine; fludarabine; Busulfan; Cytarabine

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; 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; Arabinonucleosides

Study Officials

• Chun Wang, M.D.,Ph. D.

  Shanghai General Hospital, Shanghai Jiaotong University School of Medicine

  STUDY CHAIR

Central Study Contacts

Jieling Jiang, M.D.

CONTACT

86-21-37798987; jiangjieling66@hotmail.com

Liping Wan, M.D., Ph.D.

CONTACT

86-21-37798987; wanliping924@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: director, department of hematology

Model Details: open labled randomized controlled study

Study Record Dates

• First Submitted: November 5, 2017
• First Posted: December 27, 2017
• Study Start: August 1, 2016
• Primary Completion: July 31, 2022
• Study Completion: July 31, 2022
• Last Updated: October 12, 2021

Record last verified: 2021-10

Locations

CN (1)