Early Tapering of Immunosuppressive Agents to Immunomodulation to Improve Survival of AML Patients

NCT03150134 | Unknown Phase 4 DMC

• 1 other identifier: 2017KY21
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Early reduction of immunosuppressive agents after HLA matched donor transplantation can improve the survival of advanced stage acute myeloid leukemia. single-center, open clinical study

Conditions

Acute Myeloid Leukemia; Disorder Related to Bone Marrow Transplantation

Keywords

Acute Myeloid Leukemia; transplantation; allogeneic transplantation; immunosuppressive agents

Outcome Measures

Primary Outcomes (1)

• relapse free survival(RFS)

  PFS were defined as the time from stem-cell infusion to relapse, disease progression from any cause.

  2 years

Secondary Outcomes (3)

• Progress free survival (PFS) rate

  2 years

• Overall survival rate

  2 years

• Transplant related mortality

  up to 2 year

Study Arms (2)

early reduction

EXPERIMENTAL

Usually in the absence of GvHD, immunosuppressive drugs(Cyclosporine) were gradually reduced by 6 weeks and discontinued in three months after transplant in the advanced patients while immunosuppressive agents were gradually reduced by 2 months and discontinued in four months after transplant in the advanced patients in haploidentical SCT even if complete donor chimerism (CDC) achieved. If donor chimerism had not achieved CDC with no significant acute GVHD at four weeks after HSCT, immunosuppressive agents were gradually reduced. If GvHD was present during the time of immunosuppressive agents reduction, CsA was added again and tapering was done over longer periods.

Drug: Cyclosporine

routine reduction

PLACEBO COMPARATOR

Arm/Group Descriptions.Immunosuppressive drugs(cyclosporine) were routine reduced by 3 months and discontinued in the 5 months without GvHD in the CR group. We used the result of chimerism as the reference.

Drug: routine reduction of immunosuppressive drugs(cyclosporine)

Interventions

Cyclosporine DRUG

Patients with advanced AML received early tapering of immunosuppressive drugs(Cyclosporine)

Also known as: immunosuppressive agents

early reduction

routine reduction of immunosuppressive drugs(cyclosporine) DRUG

patients with AML in CR were given the routine reduction of immunosuppressive drugs(cyclosporine)

Also known as: cyclosporine

routine reduction

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Performance status scores no more than 2 (ECOG criteria). Adequate organ function as defined by the following criteria: alanine transaminase （ALT）, aspartate transaminase（AST） and total serum bilirubin \<2×ULN (upper limit of normal) Serum creatinine and blood urea nitrogen(BUN) \<1.25×ULN. Adequate cardiac function without acute myocardial infarction, arrhythmia or atrioventricular block, heart failure, active rheumatic heart disease and cardiac dilatation(the patients has been improved after treatment of the disease and are not expected to affect transplant can include in the study).
• Absence of any other contraindications of stem cell transplantation. Willingness and ability to perform HSCT. 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 comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

You may not qualify if:

• Presence of any condition inappropriate for HSCT. Life expectancy \< 3 months because of other severe diseases. Presence of any fatal disease, including respiratory failure, heart failure, liver or kidney function failure et al.
• Uncontrolled infection. Pregnancy or breastfeeding. Has enrolled in anther clinical trials Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.

Sponsors & Collaborators

• Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine: lead

Study Sites (1)

Shanghai First People's HOSPITAL

Shanghai, Shanghai Municipality, 200127, China

RECRUITING

Related Publications (10)

• Grigg AP, Szer J, Beresford J, Dodds A, Bradstock K, Durrant S, Schwarer AP, Hughes T, Herrmann R, Gibson J, Arthur C, Matthews J. Factors affecting the outcome of allogeneic bone marrow transplantation for adult patients with refractory or relapsed acute leukaemia. Br J Haematol. 1999 Nov;107(2):409-18. doi: 10.1046/j.1365-2141.1999.01713.x.

  PMID: 10583235 RESULT

• Zander AR, Dicke KA, Keating M, Vellekoop L, Culbert S, Spitzer G, Kanojia M, Jagannath S, Schell S, Hester J, et al. Allogeneic bone marrow transplantation for acute leukemia refractory to induction chemotherapy. Cancer. 1985 Sep 15;56(6):1374-9. doi: 10.1002/1097-0142(19850915)56:63.0.co;2-c.

  PMID: 3896457 RESULT

• Duval M, Klein JP, He W, Cahn JY, Cairo M, Camitta BM, Kamble R, Copelan E, de Lima M, Gupta V, Keating A, Lazarus HM, Litzow MR, Marks DI, Maziarz RT, Rizzieri DA, Schiller G, Schultz KR, Tallman MS, Weisdorf D. Hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure. J Clin Oncol. 2010 Aug 10;28(23):3730-8. doi: 10.1200/JCO.2010.28.8852. Epub 2010 Jul 12.

  PMID: 20625136 RESULT

• Schmid C, Schleuning M, Ledderose G, Tischer J, Kolb HJ. Sequential regimen of chemotherapy, reduced-intensity conditioning for allogeneic stem-cell transplantation, and prophylactic donor lymphocyte transfusion in high-risk acute myeloid leukemia and myelodysplastic syndrome. J Clin Oncol. 2005 Aug 20;23(24):5675-87. doi: 10.1200/JCO.2005.07.061.

  PMID: 16110027 RESULT

• Liu QF, Fan ZP, Zhang Y, Jiang ZJ, Wang CY, Xu D, Sun J, Xiao Y, Tan H. Sequential intensified conditioning and tapering of prophylactic immunosuppressants for graft-versus-host disease in allogeneic hematopoietic stem cell transplantation for refractory leukemia. Biol Blood Marrow Transplant. 2009 Nov;15(11):1376-85. doi: 10.1016/j.bbmt.2009.06.017. Epub 2009 Aug 19.

  PMID: 19822296 RESULT

• Liga M, Triantafyllou E, Tiniakou M, Lambropoulou P, Karakantza M, Zoumbos NC, Spyridonidis A. High alloreactivity of low-dose prophylactic donor lymphocyte infusion in patients with acute leukemia undergoing allogeneic hematopoietic cell transplantation with an alemtuzumab-containing conditioning regimen. Biol Blood Marrow Transplant. 2013 Jan;19(1):75-81. doi: 10.1016/j.bbmt.2012.07.021. Epub 2012 Aug 4.

  PMID: 22871557 RESULT

• Elmaagacli AH, Beelen DW, Trenn G, Schmidt O, Nahler M, Schaefer UW. Induction of a graft-versus-leukemia reaction by cyclosporin A withdrawal as immunotherapy for leukemia relapsing after allogeneic bone marrow transplantation. Bone Marrow Transplant. 1999 Apr;23(8):771-7. doi: 10.1038/sj.bmt.1701672.

  PMID: 10231138 RESULT

• Rosenow F, Berkemeier A, Krug U, Muller-Tidow C, Gerss J, Silling G, Groth C, Wieacker P, Bogdanova N, Mesters R, Buchner T, Kienast J, Berdel WE, Stelljes M. CD34(+) lineage specific donor cell chimerism for the diagnosis and treatment of impending relapse of AML or myelodysplastic syndrome after allo-SCT. Bone Marrow Transplant. 2013 Aug;48(8):1070-6. doi: 10.1038/bmt.2013.2. Epub 2013 Feb 4.

  PMID: 23376821 RESULT

• Sairafi D, Remberger M, Uhlin M, Ljungman P, Ringden O, Mattsson J. Leukemia lineage-specific chimerism analysis and molecular monitoring improve outcome of donor lymphocyte infusions. Biol Blood Marrow Transplant. 2010 Dec;16(12):1728-37. doi: 10.1016/j.bbmt.2010.06.005. Epub 2010 Jun 10.

  PMID: 20542125 RESULT

• Yang J, Cai Y, Jiang J, Wan L, Bai H, Zhu J, Li S, Wang C, Song X. Early tapering of immunosuppressive agents after HLA-matched donor transplantation can improve the survival of patients with advanced acute myeloid leukemia. Ann Hematol. 2018 Mar;97(3):497-507. doi: 10.1007/s00277-017-3204-6. Epub 2017 Dec 18.

  PMID: 29250743 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Cyclosporine; Immunosuppressive Agents

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Immunologic Factors; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• xinpeng wang, doctor

  Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

  STUDY CHAIR

Central Study Contacts

jun yang yang, master

CONTACT

18001890183; yangjuan74@hotmail.com

xianminsong song, doctor

CONTACT

13501672508; shongxm@139.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 5, 2017
• First Posted: May 12, 2017
• Study Start: January 1, 2010
• Primary Completion: January 1, 2020
• Study Completion: January 1, 2021
• Last Updated: May 12, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)