Gemtuzumab Ozogamicin in Combination With A-HAM in Refractory AML (GO-A-HAM)

NCT00143975 | Completed Phase 2

• 1 other identifier: AMLSG05-04
• Study Type: interventional
• Target: 95
• Locations: 2 countries
• Sites: 27

Brief Summary

GO-A-HAM: Gemtuzumab Ozogamicin 3g/m² day 1 Cytarabine 3g/m² bid days 1-3 Mitoxantrone 12mg/m² days 2,3 All-trans Retinoic acid 45mg/m² days 4-6 and 15 mg/m² days 7-28

Conditions

Leukemia, Myeloid, Acute

Keywords

Acute myeloid leukemia; gemtuzumab ozogamicin; refractory disease

Outcome Measures

Primary Outcomes (1)

• CR-rate after therapy with GO-A-HAM

  day 30

Secondary Outcomes (3)

• kind, incidence, severity, temporal sequence and correlation of side effects of the study-drugs

  30 days

• rate of veno occlusive disease (VOD) after allogene transplantation

  100 days after allogene transplantation

• overall survival

  two years

Interventions

Cytarabine DRUG

3 g/m2 bid. i.v day 1-3

Mitoxantrone DRUG

12 mg/m2 i.v. day 2 and 3

Gemtuzumab Ozogamicin DRUG

3mg/m² i.v. day 1

All-trans-Retinoid Acid DRUG

45 mg/m2 p.o. day 4-6 15 mg/m2 p.o. day 7-28

Eligibility Criteria

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

You may qualify if:

• Acute myeloid leukemia defined according the WHO classification not responding to first induction therapy
• Age 18-60 years
• Written informed consent

You may not qualify if:

• Acute promyelocytic leukemia
• Uncontrolled infection
• Transfusion-refractory thrombocytopenia
• Pregnancy, breast-feeding, insufficient contraception
• Organ insufficiency: kidneys, liver, lungs, heart
• Severe neurological and psychiatrical interfering with informed consent
• No consent for the registration, storage and processing of data concerning the characteristics of the AML and the individual course
• Performance status \> grad 2 according the WHO classification

Sponsors & Collaborators

• University of Ulm: lead

Study Sites (27)

Department of Hematology / Oncology, University Hospital of Innsbruck

Innsbruck, A-6020, Austria

Location

St. Johann Hospital, Clinical Center of Salzburg

Salzburg, A-5020, Austria

Location

Medical Department III, Hanusch-Hospital

Vienna, A-1140, Austria

Location

Medical Department II, Central Hospital of Augsburg

Augsburg, 86156, Germany

Location

Department of General Internal Medicine, University Hospital of Bonn

Bonn, 53127, Germany

Location

Department of Hematology and Oncology, Hospital Essen-Süd, Ev. Hospital of Essen-Werden

Essen, 45239, Germany

Location

Department of Internal Medicine III, City Hospital Frankfurt am Main - Höchst

Frankfurt, 65929, Germany

Location

Medical Department IV, University Hospital of Gießen

Giessen, 35392, Germany

Location

Department of Internal Medicine, Wilhelm-Anton-Hospital gGmbH

Goch, 47574, Germany

Location

Centre of Internal Medicine, University Hospital of Göttingen

Göttingen, 37075, Germany

Location

Department of Oncology and Hematology, University Hospital Eppendorf

Hamburg, 20246, Germany

Location

Medical Department III, Clinical Center Hanau

Hanau, 63450, Germany

Location

Medical Department III, Clinical Center Hannover-Siloah

Hanover, 30449, Germany

Location

Department of Hematology, Hemostaseology and Oncology, Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Department of Internal Medicine I, University Hospital of Saarland

Homburg, 66421, Germany

Location

Medical Department II, City Hospital Karlsruhe gGmbH

Karlsruhe, 76133, Germany

Location

Medical Department II, University Hospital of Kiel

Kiel, 24116, Germany

Location

Department of Internal Medicine / Hematology and Oncology, Caritas Hospital Lebach

Lebach, 66822, Germany

Location

Department of Hematology / Oncology, Clinical center of Lüdenscheid

Lüdenscheid, 58515, Germany

Location

Department of Hematology and internal Oncology, University Hospital of Mainz

Mainz, 55101, Germany

Location

Medical Department III, Clinical Center rechts der Isar

München, 81675, Germany

Location

Department of Hematology and Oncology, Clinical Center of Oldenburg gGmbH

Oldenburg, 26133, Germany

Location

Department of Hematology and Oncology / Caritas Hospital St. Theresia

Saarbrücken, 66113, Germany

Location

Department of Oncology / Clinical Center of Stuttgart

Stuttgart, 70174, Germany

Location

Department of Internal Medicine II, University Hospital of Tübingen

Tübingen, 72076, Germany

Location

Department of Internal Medicine III, University of Ulm

Ulm, 89070, Germany

Location

Medical Department I, Helios Hospital Wuppertal

Wuppertal, 42283, Germany

Location

Related Publications (18)

• Schlenk RF, Benner A, Hartmann F, del Valle F, Weber C, Pralle H, Fischer JT, Gunzer U, Pezzutto A, Weber W, Grimminger W, Preiss J, Hensel M, Frohling S, Dohner K, Haas R, Dohner H; AML Study Group Ulm (AMLSG ULM). Risk-adapted postremission therapy in acute myeloid leukemia: results of the German multicenter AML HD93 treatment trial. Leukemia. 2003 Aug;17(8):1521-8. doi: 10.1038/sj.leu.2403009.

  PMID: 12886238 BACKGROUND

• Wheatley K, Burnett AK, Goldstone AH, Gray RG, Hann IM, Harrison CJ, Rees JK, Stevens RF, Walker H. A simple, robust, validated and highly predictive index for the determination of risk-directed therapy in acute myeloid leukaemia derived from the MRC AML 10 trial. United Kingdom Medical Research Council's Adult and Childhood Leukaemia Working Parties. Br J Haematol. 1999 Oct;107(1):69-79. doi: 10.1046/j.1365-2141.1999.01684.x.

  PMID: 10520026 BACKGROUND

• Schlenk RF, Fröhling S, Del Valle F, Dreger P, Fischer JTh, Glasmacher A, Götze K, Grimminger W, Germing U, Hartmann F, Koller E, Mergenthaler HG, Salwender H, Waterhouse C, Döhner K, Bunjes D, Döhner H. Early Allogeneic Transplantation in Patients with High Risk Acute Myeloid Leukemia Defined by Karyotype and Response To Induction Therapy: First Results of the AML HD98A Trial. Blood 98: 2822, abstract

  BACKGROUND

• Bunjes D, Buchmann I, Duncker C, Seitz U, Kotzerke J, Wiesneth M, Dohr D, Stefanic M, Buck A, Harsdorf SV, Glatting G, Grimminger W, Karakas T, Munzert G, Dohner H, Bergmann L, Reske SN. Rhenium 188-labeled anti-CD66 (a, b, c, e) monoclonal antibody to intensify the conditioning regimen prior to stem cell transplantation for patients with high-risk acute myeloid leukemia or myelodysplastic syndrome: results of a phase I-II study. Blood. 2001 Aug 1;98(3):565-72. doi: 10.1182/blood.v98.3.565.

  PMID: 11468151 BACKGROUND

• Schlenk RF, Hartmann F, Hensel M, Jung W, Weber-Nordt R, Gabler A, Haas R, Ho AD, Trumper L, Dohner H. Less intense conditioning with fludarabine, cyclophosphamide, idarubicin and etoposide (FCIE) followed by allogeneic unselected peripheral blood stem cell transplantation in elderly patients with leukemia. Leukemia. 2002 Apr;16(4):581-6. doi: 10.1038/sj.leu.2402423.

  PMID: 11960336 BACKGROUND

• Sierra J, Storer B, Hansen JA, Martin PJ, Petersdorf EW, Woolfrey A, Matthews D, Sanders JE, Storb R, Appelbaum FR, Anasetti C. Unrelated donor marrow transplantation for acute myeloid leukemia: an update of the Seattle experience. Bone Marrow Transplant. 2000 Aug;26(4):397-404. doi: 10.1038/sj.bmt.1702519.

  PMID: 10982286 BACKGROUND

• Hiddemann W, Buchner T, Essink M, Koch O, Stenzinger W, van de Loo J. High-dose cytosine arabinoside and mitoxantrone: preliminary results of a pilot study with sequential application (S-HAM) indicating a high antileukemic activity in refractory acute leukemias. Onkologie. 1988 Feb;11(1):10-2. doi: 10.1159/000216471.

  PMID: 3283619 BACKGROUND

• Hu ZB, Minden MD, McCulloch EA. Direct evidence for the participation of bcl-2 in the regulation by retinoic acid of the Ara-C sensitivity of leukemic stem cells. Leukemia. 1995 Oct;9(10):1667-73.

  PMID: 7564507 BACKGROUND

• Bradbury DA, Aldington S, Zhu YM, Russell NH. Down-regulation of bcl-2 in AML blasts by all-trans retinoic acid and its relationship to CD34 antigen expression. Br J Haematol. 1996 Sep;94(4):671-5. doi: 10.1046/j.1365-2141.1996.d01-1838.x.

  PMID: 8826891 BACKGROUND

• Benito A, Grillot D, Nunez G, Fernandez-Luna JL. Regulation and function of Bcl-2 during differentiation-induced cell death in HL-60 promyelocytic cells. Am J Pathol. 1995 Feb;146(2):481-90.

  PMID: 7856757 BACKGROUND

• Yang GS, Minden MD, McCulloch EA. Influence of schedule on regulated sensitivity of AML blasts to cytosine arabinoside. Leukemia. 1993 Jul;7(7):1012-9.

  PMID: 7686602 BACKGROUND

• Zheng A, Mantymaa P, Saily M, Savolainen E, Vahakangas K, Koistinen P. p53 pathway in apoptosis induced by all-trans-retinoic acid in acute myeloblastic leukaemia cells. Acta Haematol. 2000;103(3):135-43. doi: 10.1159/000041036.

  PMID: 10940651 BACKGROUND

• Schlenk RF, Frohling S, Hartmann F, Fischer JT, Glasmacher A, del Valle F, Grimminger W, Gotze K, Waterhouse C, Schoch R, Pralle H, Mergenthaler HG, Hensel M, Koller E, Kirchen H, Preiss J, Salwender H, Biedermann HG, Kremers S, Griesinger F, Benner A, Addamo B, Dohner K, Haas R, Dohner H; AML Study Group Ulm. Phase III study of all-trans retinoic acid in previously untreated patients 61 years or older with acute myeloid leukemia. Leukemia. 2004 Nov;18(11):1798-803. doi: 10.1038/sj.leu.2403528.

  PMID: 15385923 BACKGROUND

• Sievers EL, Larson RA, Stadtmauer EA, Estey E, Lowenberg B, Dombret H, Karanes C, Theobald M, Bennett JM, Sherman ML, Berger MS, Eten CB, Loken MR, van Dongen JJ, Bernstein ID, Appelbaum FR; Mylotarg Study Group. Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. J Clin Oncol. 2001 Jul 1;19(13):3244-54. doi: 10.1200/JCO.2001.19.13.3244.

  PMID: 11432892 BACKGROUND

• De Angelo, D., et al., Interim analysis of a phase II study of the safety and efficacy of Gemtuzumab Ozogamicin (Mylotarg) given in combination with Cytarabine and Daunorubicin in patients< 60years old with untreated acute myeloid leukemia. Blood 100:745a.

  BACKGROUND

• Jonathan W. Kell, Alan K. Burnett, Raj Chopra, John Yin, Dominic Culligan, Richard Clark, Ann Hunter, Ama Rohatiner, Don W. Milligan, Nigel Russell, Archie Prentice. Dept of Haematology, MRC AML Pilot Group, United Kingdom Mylotarg (Gemtuzumab Ozogamicin: GO) Given Simultaneously with Intensive Induction and/or Consolidation Therapy for AML Is Feasible and May Improve the Response Rate. Blood 100:746a

  BACKGROUND

• Wadleigh M, Richardson PG, Zahrieh D, Lee SJ, Cutler C, Ho V, Alyea EP, Antin JH, Stone RM, Soiffer RJ, DeAngelo DJ. Prior gemtuzumab ozogamicin exposure significantly increases the risk of veno-occlusive disease in patients who undergo myeloablative allogeneic stem cell transplantation. Blood. 2003 Sep 1;102(5):1578-82. doi: 10.1182/blood-2003-01-0255. Epub 2003 May 8.

  PMID: 12738663 BACKGROUND

• Hutter-Kronke ML, Benner A, Dohner K, Krauter J, Weber D, Moessner M, Kohne CH, Horst HA, Schmidt-Wolf IG, Rummel M, Gotze K, Koller E, Petzer AL, Salwender H, Fiedler W, Kirchen H, Haase D, Kremers S, Theobald M, Matzdorff AC, Ganser A, Dohner H, Schlenk RF. Salvage therapy with high-dose cytarabine and mitoxantrone in combination with all-trans retinoic acid and gemtuzumab ozogamicin in acute myeloid leukemia refractory to first induction therapy. Haematologica. 2016 Jul;101(7):839-45. doi: 10.3324/haematol.2015.141622. Epub 2016 Apr 1.

  PMID: 27036160 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Disease

Interventions

Cytarabine; Mitoxantrone; Gemtuzumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds; Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Richard F Schlenk, Dr. med.

  University of Ulm / Department of Internal Medicine III

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 31, 2005
• First Posted: September 2, 2005
• Study Start: June 1, 2004
• Primary Completion: July 1, 2007
• Study Completion: June 1, 2009
• Last Updated: August 12, 2010

Record last verified: 2010-08

Locations

DE (24); AU (3)