Donor-specific Allogeneic Hematopoietic Cell Transplantation for Acute Lymphoblastic Leukemia (ALL) (AHCTALL)

This study is currently recruiting participants.

Verified January 2013 by Asan Medical Center

Sponsor:

Information provided by (Responsible Party):

Dae-Young Kim, Asan Medical Center

ClinicalTrials.gov Identifier:

NCT01037764

First received: December 22, 2009

Last updated: January 3, 2013

Last verified: January 2013

History of Changes

Purpose

[Study Objectives]

To evaluate the efficacy of allogeneic hematopoietic cell transplantation (HCT) in patients with acute lymphoblastic leukemia (ALL) in the first or second complete remission (CR). The efficacy of the treatment will be measured in terms of the frequency of relapse and duration of remission (the primary endpoints).
The secondary end points of the study include; engraftment, donor chimerism, secondary graft failure, acute and chronic graft-versus-host disease (GVHD), immune recovery, infections, transplantation-related mortality, leukemia free survival, and overall survival.

Condition	Intervention	Phase
Acute Lymphoid Leukemia	Procedure: hematopoietic cell transplantation	Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Allogeneic Hematopoietic Cell Transplantation for Patients With Acute Lymphoblastic Leukemia in Remission Using HLA-matched Sibling Donors, HLA-matched Unrelated Donors, or HLA-mismatched Familial Donors-A Phase 2 Study

Resource links provided by NLM:

MedlinePlus related topics: Chronic Lymphocytic Leukemia Leukemia

U.S. FDA Resources

Further study details as provided by Asan Medical Center:

Primary Outcome Measures:

Cumulative incidence of relapse [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

leukemia free survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
engraftment rate [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
donor chimerism [ Time Frame: 1year, 2year, 3year ] [ Designated as safety issue: No ]
secondary graft failure rate [ Time Frame: 100days, 1year ] [ Designated as safety issue: Yes ]
Incidence & severity of acute GVHD [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
incidence and severity of chronic GVHD [ Time Frame: 1year, 2year, 3year ] [ Designated as safety issue: Yes ]
degree of immune recovery [ Time Frame: 6 months, 1year ] [ Designated as safety issue: Yes ]
cumulative incidence and severity of infection [ Time Frame: 3years ] [ Designated as safety issue: Yes ]
transplantation-related mortality rate [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
overall survival rate & median survival time [ Time Frame: 3 years ] [ Designated as safety issue: No ]
duration of remission [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	100
Study Start Date:	January 2010
Estimated Study Completion Date:	December 2016
Estimated Primary Completion Date:	December 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: HCT recipient For HLA-matched sibling HCT, if a patient is 55 years old or less and without co-morbidity, the patient will receive Bu-Cy conditioning therapy and be transplanted with bone marrow cells. Patients who are older than 55 years or with co-morbidity will receive Bu-Flu-ATG conditioning and be transplanted with mobilized peripheral blood hematopoietic cells. For HLA-matched unrelated donor or HLA-mismatched familial donor HCT, the patient will receive Bu-Flu-ATG conditioning and well be transplanted with mobilized peripheral blood hematopoietic cells.	Procedure: hematopoietic cell transplantation Bu-Cy conditioning; Busulfan (Bu) 3.2 mg/kg/day iv daily on days -7 and -4. Cyclophosphamide (Cy) 60 mg/kg in D5W 200 mL iv over 1-2 hours daily on days -3 and -2. BuFluATG conditioning; Bu 3.2 mg/kg*/day iv daily on days -7 and -6. Fludarabine (Flu) 30 mg/m2/day in D5W 100 ml iv over 30 minutes starting at 4 pm daily on days -7, -6, -5, -4, -3, and -2. Anti-thymocyte globulin (ATG, Thymoglobulin, Genzyme Transplant, Cambridge, MA, USA) 1.5 mg/kg/day (for HLA-matched sibling HCT) or 3.0 mg/kg/day (for HLA-matched unrelated donor HCT or HLA-mismatched familial donor HCT) in N/S 500-800 ml (less than 4 mg/ml) iv over 4 hours starting at 8 am daily on days , -3, -2 and -1. Other Name: allogeneic hematopoietic stem cell transplantation

Arms

Assigned Interventions

Experimental: HCT recipient

For HLA-matched sibling HCT, if a patient is 55 years old or less and without co-morbidity, the patient will receive Bu-Cy conditioning therapy and be transplanted with bone marrow cells. Patients who are older than 55 years or with co-morbidity will receive Bu-Flu-ATG conditioning and be transplanted with mobilized peripheral blood hematopoietic cells. For HLA-matched unrelated donor or HLA-mismatched familial donor HCT, the patient will receive Bu-Flu-ATG conditioning and well be transplanted with mobilized peripheral blood hematopoietic cells.

Procedure: hematopoietic cell transplantation

Bu-Cy conditioning; Busulfan (Bu) 3.2 mg/kg*/day iv daily on days -7 and -4. Cyclophosphamide (Cy) 60 mg/kg* in D5W 200 mL iv over 1-2 hours daily on days -3 and -2.

BuFluATG conditioning; Bu 3.2 mg/kg*/day iv daily on days -7 and -6. Fludarabine (Flu) 30 mg/m2/day in D5W 100 ml iv over 30 minutes starting at 4 pm daily on days -7, -6, -5, -4, -3, and -2.

Anti-thymocyte globulin (ATG, Thymoglobulin, Genzyme Transplant, Cambridge, MA, USA) 1.5 mg/kg/day (for HLA-matched sibling HCT) or 3.0 mg/kg/day (for HLA-matched unrelated donor HCT or HLA-mismatched familial donor HCT) in N/S 500-800 ml (less than 4 mg/ml) iv over 4 hours starting at 8 am daily on days , -3, -2 and -1.

Other Name: allogeneic hematopoietic stem cell transplantation

Show Detailed Description

Eligibility

Ages Eligible for Study:	15 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with ALL who achieve CR after induction chemotherapy.
Patients with recurrent ALL that went into second CR after salvage chemotherapy, except those who had undergone allogeneic HCT previously.
Patients should be 15 years of age or more, and 75 years of age or less.
The performance status of the patients should be 70 or over by Karnofsky performance scale.
Patients should have adequate hepatic function (bilirubin less than 2.0 mg/dl, AST less than three times the upper normal limit).
Patients must have adequate renal function (creatinine less than 2.0 mg/dl).
Patients must have adequate cardiac function (ejection fraction > 40% on MUGA scan).
Patients must sign informed consent.

Exclusion Criteria:

Presence of significant active infection
Presence of uncontrolled bleeding
Any coexisting major illness or organ failure
Patients with psychiatric disorder or mental deficiency severe as to make compliance with the treatment unlike, and making informed consent impossible
Nursing women, pregnant women, women of childbearing potential who do not want adequate contraception
Patients with a diagnosis of prior malignancy unless disease-free for at least 5 years following therapy with curative intent (except curatively treated nonmelanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01037764

Contacts

Contact: Young-Shin Lee, R.N.	82-2-3010-6892	lysinkorea@amc.seoul.kr
Contact: Young-Ah Kang, R.N.	82-2-3010-6375	kya@amc.seoul.kr

Locations

Korea, Republic of
Inje University Haeundae Paik Hospital	Recruiting
Pusan, Korea, Republic of
Contact: Yeon-Joo Lee, RN 82-10-3342-3043 joop75@lycos.co.kr
Principal Investigator: Young-Don Joo, MD, PhD
Asan Medical Center	Recruiting
Seoul, Korea, Republic of, 138-736
Contact: Young-Shin Lee, RN 82-2-3010-6982 lysinkorea@amc.seoul.kr
Sub-Investigator: Kyoo-Hyung Lee, M.D. & PhD
Sub-Investigator: Je-Hwan Lee, M.D. & PhD
Sub-Investigator: Jung-Hee Lee, M.D. & PhD.
Principal Investigator: Dae-Young Kim, M.D.

Sponsors and Collaborators

Asan Medical Center

Investigators

Principal Investigator:	Dae-Young Kim, M.D.	Asan Medical Center
Study Chair:	Kyoo-Hyung Lee, M.D. & PhD.	Asan Medical Center
Study Director:	Je-Hwan Lee, M.D. & PhD.	Asan Medical Center
Study Director:	Jung-Hee Lee, M.D. & PhD.	Asan Medical Center
Study Director:	Young-Don Joo, MD, PhD	Inje University

More Information

Publications:

Jamieson CH, Amylon MD, Wong RM, Blume KG. Allogeneic hematopoietic cell transplantation for patients with high-risk acute lymphoblastic leukemia in first or second complete remission using fractionated total-body irradiation and high-dose etoposide: a 15-year experience. Exp Hematol. 2003 Oct;31(10):981-6.

Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK, Burnett AK, Chopra R, Wiernik PH, Foroni L, Paietta E, Litzow MR, Marks DI, Durrant J, McMillan A, Franklin IM, Luger S, Ciobanu N, Rowe JM. In adults with standard-risk acute lymphoblastic leukemia (ALL) the greatest benefit is achieved from a matched sibling allogeneic transplant in first complete remission (CR) and an autologous transplant is less effective than conventional consolidation/maintenance chemotherapy in All patients : final results of the international ALL trial (MRC UKALL XII/ ECOG E2993). Blood. 2007 Nov 29; [Epub ahead of print]

Barker JN, Krepski TP, DeFor TE, Davies SM, Wagner JE, Weisdorf DJ. Searching for unrelated donor hematopoietic stem cells: availability and speed of umbilical cord blood versus bone marrow. Biol Blood Marrow Transplant. 2002;8(5):257-60.

Powles RL, Morgenstern GR, Kay HE, McElwain TJ, Clink HM, Dady PJ, Barrett A, Jameson B, Depledge MH, Watson JG, Sloane J, Leigh M, Lumley H, Hedley D, Lawler SD, Filshie J, Robinson B. Mismatched family donors for bone-marrow transplantation as treatment for acute leukaemia. Lancet. 1983 Mar 19;1(8325):612-5.

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.

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. Epub 2005 Mar 7.

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.

Lacerda JF, Martins C, Carmo JA, Lourenço F, Juncal C, Rodrigues A, Vilalobos I, Moura MC, Ligeiro D, Martinho A, Lacerda JM. Haploidentical stem cell transplantation with purified CD34 cells after a chemotherapy-alone conditioning regimen. Biol Blood Marrow Transplant. 2003 Oct;9(10):633-42.

Huang XJ, Liu DH, Liu KY, Xu LP, Chen H, Han W, Chen YH, Wang JZ, Gao ZY, Zhang YC, Jiang Q, Shi HX, Lu DP. Haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion for the treatment of hematological malignancies. Bone Marrow Transplant. 2006 Aug;38(4):291-7. Erratum in: Bone Marrow Transplant. 2008 Aug;42(4):295. Dosage error in article text.

Kanda Y, Oshima K, Asano-Mori Y, Kandabashi K, Nakagawa M, Sakata-Yanagimoto M, Izutsu K, Hangaishi A, Tsujino S, Ogawa S, Motokura T, Chiba S, Hirai H. In vivo alemtuzumab enables haploidentical human leukocyte antigen-mismatched hematopoietic stem-cell transplantation without ex vivo graft manipulation. Transplantation. 2005 May 27;79(10):1351-7.

DiJerome L. The nursing case management computerized system: meeting the challenge of health care delivery through technology. Comput Nurs. 1992 Nov-Dec;10(6):250-8.

Ichinohe T, Uchiyama T, Shimazaki C, Matsuo K, Tamaki S, Hino M, Watanabe A, Hamaguchi M, Adachi S, Gondo H, Uoshima N, Yoshihara T, Hatanaka K, Fujii H, Kawa K, Kawanishi K, Oka K, Kimura H, Itoh M, Inukai T, Maruya E, Saji H, Kodera Y; Japanese Collaborative Study Group for NIMA-Complementary Haploidentical Stem Cell Transplantation. Feasibility of HLA-haploidentical hematopoietic stem cell transplantation between noninherited maternal antigen (NIMA)-mismatched family members linked with long-term fetomaternal microchimerism. Blood. 2004 Dec 1;104(12):3821-8. Epub 2004 Jul 27.

McSweeney PA, Niederwieser D, Shizuru JA, Sandmaier BM, Molina AJ, Maloney DG, Chauncey TR, Gooley TA, Hegenbart U, Nash RA, Radich J, Wagner JL, Minor S, Appelbaum FR, Bensinger WI, Bryant E, Flowers ME, Georges GE, Grumet FC, Kiem HP, Torok-Storb B, Yu C, Blume KG, Storb RF. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood. 2001 Jun 1;97(11):3390-400.

Hegenbart U, Niederwieser D, Sandmaier BM, Maris MB, Shizuru JA, Greinix H, Cordonnier C, Rio B, Gratwohl A, Lange T, Al-Ali H, Storer B, Maloney D, McSweeney P, Chauncey T, Agura E, Bruno B, Maziarz RT, Petersen F, Storb R. Treatment for acute myelogenous leukemia by low-dose, total-body, irradiation-based conditioning and hematopoietic cell transplantation from related and unrelated donors. J Clin Oncol. 2006 Jan 20;24(3):444-53. Epub 2005 Dec 12.

Lee KH, Lee JH, Lee JH, Kim WK, Chi HS, Lee JS. Non-myeloablative conditioning regimen of fludarabine, busulfan, anti-thymocyte globulin, and methylprednisolone for allogeneic peripheral blood hematopoietic cell transplantation. Haematologica. 2001 Sep;86(9):999-1001. No abstract available.

Alyea EP, Kim HT, Ho V, Cutler C, Gribben J, DeAngelo DJ, Lee SJ, Windawi S, Ritz J, Stone RM, Antin JH, Soiffer RJ. Comparative outcome of nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation for patients older than 50 years of age. Blood. 2005 Feb 15;105(4):1810-4. Epub 2004 Sep 30.

Giralt S, Thall PF, Khouri I, Wang X, Braunschweig I, Ippolitti C, Claxton D, Donato M, Bruton J, Cohen A, Davis M, Andersson BS, Anderlini P, Gajewski J, Kornblau S, Andreeff M, Przepiorka D, Ueno NT, Molldrem J, Champlin R. Melphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation. Blood. 2001 Feb 1;97(3):631-7.

Cina RA, Wikiel KJ, Lee PW, Cameron AM, Hettiarachy S, Rowland H, Goodrich J, Colby C, Spitzer TR, Neville DM Jr, Huang CA. Stable multilineage chimerism without graft versus host disease following nonmyeloablative haploidentical hematopoietic cell transplantation. Transplantation. 2006 Jun 27;81(12):1677-85.

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Vanclée A, Lutgens LC, Oving EB, Deutz NE, Gijbels MJ, Schouten HC, Bos GM. Keratinocyte growth factor ameliorates acute graft-versus-host disease in a novel nonmyeloablative haploidentical transplantation model. Bone Marrow Transplant. 2005 Nov;36(10):907-15.

Fischer A, Durandy A, de Villartay JP, Vilmer E, Le Deist F, Gérota I, Griscelli C. HLA-haploidentical bone marrow transplantation for severe combined immunodeficiency using E rosette fractionation and cyclosporine. Blood. 1986 Feb;67(2):444-9.

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Sykes M, Preffer F, McAfee S, Saidman SL, Weymouth D, Andrews DM, Colby C, Sackstein R, Sachs DH, Spitzer TR. Mixed lymphohaemopoietic chimerism and graft-versus-lymphoma effects after non-myeloablative therapy and HLA-mismatched bone-marrow transplantation. Lancet. 1999 May 22;353(9166):1755-9.

Spitzer TR, McAfee SL, Dey BR, Colby C, Hope J, Grossberg H, Preffer F, Shaffer J, Alexander SI, Sachs DH, Sykes M. Nonmyeloablative haploidentical stem-cell transplantation using anti-CD2 monoclonal antibody (MEDI-507)-based conditioning for refractory hematologic malignancies. Transplantation. 2003 May 27;75(10):1748-51.

O'Donnell PV, Luznik L, Jones RJ, Vogelsang GB, Leffell MS, Phelps M, Rhubart P, Cowan K, Piantados S, Fuchs EJ. Nonmyeloablative bone marrow transplantation from partially HLA-mismatched related donors using posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2002;8(7):377-86.

Tamaki H, Ikegame K, Kawakami M, Fujioka T, Tsuboi A, Oji Y, Oka Y, Sugiyama H, Kawase I, Ogawa H. Successful engraftment of HLA-haploidentical related transplants using nonmyeloablative conditioning with fludarabine, busulfan and anti-T-lymphocyte globulin. Leukemia. 2003 Oct;17(10):2052-4. No abstract available.

Byrd JC, Mrozek K, Dodge RK, Carroll AJ, Edwards CG, Arthur DC, Pettenati MJ, Patil SR, Rao KW, Watson MS, Koduru PR, Moore JO, Stone RM, Mayer RJ, Feldman EJ, Davey FR, Schiffer CA, Larson RA, Bloomfield CD. Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood. 2002 Dec 15;100(13):4325-36.

Lee KH, Lee JH, Lee JH, Kim DY, Kim SH, Shin HJ, Lee YS, Kang YA, Seol M, Ryu SG. Hematopoietic cell transplantation from an HLA-mismatched familial donor is feasible without ex vivo-T cell depletion after reduced-intensity conditioning with busulfan, fludarabine, and antithymocyte globulin. Biol Blood Marrow Transplant. 2009 Jan;15(1):61-72.

Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005 Dec;11(12):945-56.

Responsible Party:	Dae-Young Kim, Assistant Professor, Asan Medical Center
ClinicalTrials.gov Identifier:	NCT01037764 History of Changes
Other Study ID Numbers:	AMC-ALLO-036
Study First Received:	December 22, 2009
Last Updated:	January 3, 2013
Health Authority:	Korea: Institutional Review Board

Keywords provided by Asan Medical Center:

acute lymphoid leukemia
primary complete remission
secondary complete remission
postremission therapy
allogeneic hematopoietic cell transplantation

Additional relevant MeSH terms:

Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms

Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on May 16, 2013

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