Family-mismatched/Haploidentical Donors Versus Matched Unrelated Donors

NCT01751997 | Completed Phase 2

• 1 other identifier: CBMTC-AML-1
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

Brief Summary

This study will compare the clinical outcomes of transplants from family-mismatched/haploidentical donors (FMT) with transplants from 8/8-matched unrelated donor (MUT), which is a current gold standard donors when lacking of HLA-matched-siblings

1. 1.Primary objectives: Overall survival of FMT may be similar to that of MUT
2. 2.Secondary objectives:

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Overall survival

  Overall survival is defined as the time interval between date of enrollment and death from any cause or for surviving patients, to last follow-up

  annually through 3 years

Secondary Outcomes (16)

• Neutrophil recovery

  56 days

• Primary Graft failure

  56 days

• Secondary Graft failure

  100 days

• Platelet recovery

  100 days and 180 days

• Donor cell engraftment

  56 days

Study Arms (2)

Transplants from 8/8-matched unrelated

ACTIVE COMPARATOR

Participants will receive transplants from 8/8-matched unrelated donors using myeloablative or reduced-intensity conditioning according to age or comorbidity.

Drug: Transplants from 8/8-matched Unrelated donors

Transplants from family-mismatched/haploidentical donors

EXPERIMENTAL

Participants will receive FMT using a reduced intensity conditioning regimens.

Drug: Transplants from family-mismatched/haploidentical donors

Interventions

Transplants from 8/8-matched Unrelated donors DRUG

* Myeloablative conditioning 1. Total body irradiation; 165 cGy, every 12 hours, 8 doses, days -7 to -4 (total 1320 cGy) 2. Cyclophosphamide; 60 mg/kg/day, IV for 30 minutes, days -3 to -2 (total 120 mg/kg) 3. Antithymocyte globulin (ATG); 1.25 mg/kg/day, IV for 6 hours, days -3 to -2, (total 2.5 mg/kg) * Reduced-intensity conditioning; older patients (age \> 55 years) and/or patients with comorbidities 1. Fludarabine; 30 mg/m\^2/day, IV for 1 hour, days -8 to -4 (total 150 mg/m\^2) 2. Busulfex; 3.2 mg/kg/day, IV for 3 hours, days -3 to -2 (total 6.4 mg/kg) 3. Total body irradiation; 200 cGy, every 12 hours 2 doses, days -1 (total 400 cGy) 4. ATG; 1.25 mg/kg/day, IV for 6 hours, days -3 to -2, (total 2.5 mg/kg) * GVHD prophylaxis 1. Tacrolimus; 0.03 mg/kg/day, IV for 24 hours from day -1 (0.12 mg/kg/day, PO, if tolerable) 2. Methotrexate; 5 mg/m\^2/day, IV push, days +1, +3, +6, +11

Transplants from 8/8-matched unrelated

Transplants from family-mismatched/haploidentical donors DRUG

* Reduced-intensity conditioning 1. Total body irradiation; 200 cGy, every 12 hours, 4 doses, days -9 to -8 (total 800 cGy) 2. Fludarabine; 30 mg/m\^2/day, IV for 1 hour, days -7 to -3 (total 150 mg/m\^2) 3. Busulfex; 3.2 mg/kg/day, IV for 3 hours, days -6 to -5 (total 6.4 mg/kg) 4. ATG; 1.25 mg/kg/day, IV for 6 hours, days -4 to -1 (total 5.0 mg/kg) * GVHD prophylaxis 1. Tacrolimus; 0.03 mg/kg/day, IV for 24 hours from day -1 (0.12 mg/kg/day, PO, if tolerable) 2. Methotrexate; 5 mg/m\^2/day, IV push, days +1, +3, +6, +11

Transplants from family-mismatched/haploidentical donors

Eligibility Criteria

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

You may qualify if:

• Patients with AML aged from 18 to 65 years
• Eastern Cooperative Oncology Group (ECOG) performance \< 2
• High risk group for relapse
• Complete remission (CR) 1 with unfavorable prognostic factor; presenting white blood cell \> 100,000/microliter or prior myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) or MDS/MPN or cytogenetics \& molecular features (intermediate and adverse)
• CR2 or CR3 at transplantation
• No HLA-matched sibling and unrelated donor (HLA-A, -B, -C, and -DRB1)
• Acceptable organ function defined as serum creatinine \< 2 mg/dl, unless considered due to leukemia and serum bilirubin \< 3 mg/dl, unless considered due to leukemia
• Written informed consent form

You may not qualify if:

• Active uncontrolled infections
• Corrected pulmonary diffusion capacity of \<40%
• Cardiac ejection fraction of \<35%
• ECOG performance status :2, 3, 4
• Active central nervous system involvement of disease
• Serological evidence of infection with HIV
• Pregnancy or breastfeeding
• Patient who are not suitable for the trial in accordance with principal investigator's decision

Sponsors & Collaborators

• Byung-Sik Cho: lead

Study Sites (1)

Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital

Seoul, 137-701, South Korea

Location

Related Publications (12)

• Aversa F. Haploidentical haematopoietic stem cell transplantation for acute leukaemia in adults: experience in Europe and the United States. Bone Marrow Transplant. 2008 Mar;41(5):473-81. doi: 10.1038/sj.bmt.1705966. Epub 2008 Jan 7.

  PMID: 18176612 BACKGROUND

• Ruggeri A, Ciceri F, Gluckman E, Labopin M, Rocha V; Eurocord and Acute Leukemia Working Party of the European Blood and Marrow Transplant Group. Alternative donors hematopoietic stem cells transplantation for adults with acute myeloid leukemia: Umbilical cord blood or haploidentical donors? Best Pract Res Clin Haematol. 2010 Jun;23(2):207-16. doi: 10.1016/j.beha.2010.06.002.

  PMID: 20837332 BACKGROUND

• Yakoub-Agha I, Mesnil F, Kuentz M, Boiron JM, Ifrah N, Milpied N, Chehata S, Esperou H, Vernant JP, Michallet M, Buzyn A, Gratecos N, Cahn JY, Bourhis JH, Chir Z, Raffoux C, Socie G, Golmard JL, Jouet JP; French Society of Bone Marrow Transplantation and Cell Therapy. Allogeneic marrow stem-cell transplantation from human leukocyte antigen-identical siblings versus human leukocyte antigen-allelic-matched unrelated donors (10/10) in patients with standard-risk hematologic malignancy: a prospective study from the French Society of Bone Marrow Transplantation and Cell Therapy. J Clin Oncol. 2006 Dec 20;24(36):5695-702. doi: 10.1200/JCO.2006.08.0952. Epub 2006 Nov 20.

  PMID: 17116940 BACKGROUND

• Beatty PG, Clift RA, Mickelson EM, Nisperos BB, Flournoy N, Martin PJ, Sanders JE, Stewart P, Buckner CD, Storb R, et al. Marrow transplantation from related donors other than HLA-identical siblings. N Engl J Med. 1985 Sep 26;313(13):765-71. doi: 10.1056/NEJM198509263131301.

  PMID: 3897863 BACKGROUND

• Anasetti C, Hansen JA. Effect of HLA incompatibility in marrow transplantation from unrelated and HLA-mismatched related donors. Transfus Sci. 1994 Sep;15(3):221-30. doi: 10.1016/0955-3886(94)90134-1.

  PMID: 10155543 BACKGROUND

• Henslee-Downey PJ, Abhyankar SH, Parrish RS, Pati AR, Godder KT, Neglia WJ, Goon-Johnson KS, Geier SS, Lee CG, Gee AP. Use of partially mismatched related donors extends access to allogeneic marrow transplant. Blood. 1997 May 15;89(10):3864-72.

  PMID: 9160695 BACKGROUND

• Aversa F, Terenzi A, Tabilio A, Falzetti F, Carotti A, Ballanti S, Felicini R, Falcinelli F, Velardi A, Ruggeri L, Aloisi T, Saab JP, Santucci A, Perruccio K, Martelli MP, Mecucci C, Reisner Y, Martelli MF. Full haplotype-mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. J Clin Oncol. 2005 May 20;23(15):3447-54. doi: 10.1200/JCO.2005.09.117. Epub 2005 Mar 7.

  PMID: 15753458 BACKGROUND

• Ruggeri L, Mancusi A, Capanni M, Urbani E, Carotti A, Aloisi T, Stern M, Pende D, Perruccio K, Burchielli E, Topini F, Bianchi E, Aversa F, Martelli MF, Velardi A. Donor natural killer cell allorecognition of missing self in haploidentical hematopoietic transplantation for acute myeloid leukemia: challenging its predictive value. Blood. 2007 Jul 1;110(1):433-40. doi: 10.1182/blood-2006-07-038687. Epub 2007 Mar 19.

  PMID: 17371948 BACKGROUND

• Ciceri F, Labopin M, Aversa F, Rowe JM, Bunjes D, Lewalle P, Nagler A, Di Bartolomeo P, Lacerda JF, Lupo Stanghellini MT, Polge E, Frassoni F, Martelli MF, Rocha V; Acute Leukemia Working Party (ALWP) of European Blood and Marrow Transplant (EBMT) Group. A survey of fully haploidentical hematopoietic stem cell transplantation in adults with high-risk acute leukemia: a risk factor analysis of outcomes for patients in remission at transplantation. Blood. 2008 Nov 1;112(9):3574-81. doi: 10.1182/blood-2008-02-140095. Epub 2008 Jul 7.

  PMID: 18606875 BACKGROUND

• Huang XJ, Liu DH, Liu KY, Xu LP, Chen H, Han W, Chen YH, Zhang XH, Lu DP. Treatment of acute leukemia with unmanipulated HLA-mismatched/haploidentical blood and bone marrow transplantation. Biol Blood Marrow Transplant. 2009 Feb;15(2):257-65. doi: 10.1016/j.bbmt.2008.11.025.

  PMID: 19167686 BACKGROUND

• Cho BS, Yoon JH, Shin SH, Yahng SA, Lee SE, Eom KS, Kim YJ, Lee S, Min CK, Cho SG, Kim DW, Lee JW, Min WS, Park CW, Kim HJ. Comparison of allogeneic stem cell transplantation from familial-mismatched/haploidentical donors and from unrelated donors in adults with high-risk acute myelogenous leukemia. Biol Blood Marrow Transplant. 2012 Oct;18(10):1552-63. doi: 10.1016/j.bbmt.2012.04.008. Epub 2012 Apr 16.

  PMID: 22516055 BACKGROUND

• Cho BS, Min GJ, Park S, Park SS, Shin SH, Yahng SA, Jeon YW, Yoon JH, Lee SE, Eom KS, Kim YJ, Lee S, Min CK, Cho SG, Kim DW, Lee JW, Kim M, Kim Y, Kim HJ. Haploidentical vs matched unrelated donor transplantation for acute myeloid leukemia in remission: A prospective comparative study. Am J Hematol. 2021 Jan;96(1):98-109. doi: 10.1002/ajh.25993. Epub 2020 Nov 24.

  PMID: 32905642 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

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

Study Officials

• Hee-Je Kim, MD, PhD

  Seoul St. Mary's Hematology Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: December 14, 2012
• First Posted: December 18, 2012
• Study Start: January 1, 2013
• Primary Completion: May 21, 2019
• Study Completion: December 31, 2019
• Last Updated: April 19, 2024

Record last verified: 2024-04

Locations

KR (1)