Combination Chemotherapy With or Without Gemtuzumab Ozogamicin or Tipifarnib in Treating Patients With Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes

NCT00454480 | Completed Phase 2

• 6 other identifiers: CDR0000526121UHW-AML16EU-20677ISRCTN11036523EUDRACT-2005-002846-14MREC-CU106
• Study Type: interventional
• Target: 2,000
• Locations: 1 country
• Sites: 96

Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as gemtuzumab ozogamicin, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy together with gemtuzumab ozogamicin or tipifarnib may kill more cancer cells. PURPOSE: This randomized phase II/III trial is studying different combination chemotherapy regimens to compare how well they work when given with or without gemtuzumab ozogamicin or tipifarnib in treating patients with acute myeloid leukemia or high-risk myelodysplastic syndromes.

Conditions

Leukemia; Myelodysplastic Syndromes

Keywords

untreated adult acute myeloid leukemia; de novo myelodysplastic syndromes; secondary acute myeloid leukemia; secondary myelodysplastic syndromes; previously treated myelodysplastic syndromes; refractory anemia with excess blasts; adult acute basophilic leukemia; adult acute eosinophilic leukemia; adult acute megakaryoblastic leukemia (M7); adult acute minimally differentiated myeloid leukemia (M0); adult acute monoblastic leukemia (M5a); adult acute monocytic leukemia (M5b); adult acute myeloblastic leukemia with maturation (M2); adult acute myeloblastic leukemia without maturation (M1); adult erythroleukemia (M6a); adult pure erythroid leukemia (M6b); adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); adult acute myelomonocytic leukemia (M4); childhood myelodysplastic syndromes

Outcome Measures

Primary Outcomes (5)

• Overall survival

• Achievement of complete remission and reasons for failure

• Duration of remission, relapse rates, and deaths

• Hematological and nonhematological toxicity

• Supportive care requirements (and other aspects of health economics)

Interventions

alemtuzumab BIOLOGICAL

arsenic trioxide DRUG

azacitidine DRUG

busulfan DRUG

clofarabine DRUG

cytarabine DRUG

daunorubicin hydrochloride DRUG

fludarabine phosphate DRUG

gemtuzumab ozogamicin DRUG

melphalan DRUG

tipifarnib DRUG

DNA methylation analysis GENETIC

cytogenetic analysis GENETIC

gene expression analysis GENETIC

mutation analysis GENETIC

diagnostic laboratory biomarker analysis OTHER

immunologic technique OTHER

allogeneic hematopoietic stem cell transplantation PROCEDURE

nonmyeloablative allogeneic hematopoietic stem cell transplantation PROCEDURE

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Diagnosis of 1 of the following: * Acute myeloid leukemia (AML) meeting the following criteria: * De novo or secondary AML * No acute promyelocytic leukemia * High-risk myelodysplastic syndromes (\> 10% marrow blasts; refractory anemia with excess blasts-2) * No blast transformation of chronic myeloid leukemia * Patients ≤ 60 years of age may be eligible provided they are considered unfit for clinical trial MRC-AMLI5 PATIENT CHARACTERISTICS: * Not pregnant or nursing * AST and ALT ≤ 2 times upper limit of normal (ULN) (for patients receiving gemtuzumab ozogamicin) * Bilirubin ≤ 2 times ULN (for patients receiving gemtuzumab ozogamicin) * Creatinine normal (for patients receiving clofarabine) * No other concurrent active malignancy except basal cell carcinoma PRIOR CONCURRENT THERAPY: * No prior cytotoxic chemotherapy for AML * Hydroxyurea or similar low-dose therapy to control WBC count prior to initiation of intensive therapy allowed * No concurrent enzyme anticonvulsants, including phenytoin, phenobarbital, primidone, carbamazepine, or oxcarbazepine (for patients receiving tipifarnib)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• The University of New South Wales: lead

Study Sites (96)

Basingstoke and North Hampshire NHS Foundation Trust

Basingstoke, England, RG24 9NA, United Kingdom

Location

Royal United Hospital

Bath, England, BA1 3NG, United Kingdom

Location

Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust

Birmingham, England, B15 2TH, United Kingdom

Location

Birmingham Heartlands Hospital

Birmingham, England, B9 5SS, United Kingdom

Location

Blackpool Victoria Hospital

Blackpool, England, FY3 8NR, United Kingdom

Location

Royal Bournemouth Hospital

Bournemouth, England, BH7 7DW, United Kingdom

Location

Bradford Royal Infirmary

Bradford, England, BD9 6RJ, United Kingdom

Location

Sussex Cancer Centre at Royal Sussex County Hospital

Brighton, England, BN2 5BE, United Kingdom

Location

Queen's Hospital

Burton-on-Trent, England, DE13 0RB, United Kingdom

Location

West Suffolk Hospital

Bury St Edmunds, England, IP33 2QZ, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, England, CB2 2QQ, United Kingdom

Location

Kent and Canterbury Hospital

Canterbury, England, CT1 3NG, United Kingdom

Location

St. Helier Hospital

Carshalton, England, SM5 1AA, United Kingdom

Location

Gloucestershire Oncology Centre at Cheltenham General Hospital

Cheltenham, England, GL53 7AN, United Kingdom

Location

Countess of Chester Hospital

Chester, England, CH2 1UL, United Kingdom

Location

Chesterfield Royal Hospital

Chesterfield, England, S44 5BL, United Kingdom

Location

Saint Richards Hospital

Chichester, England, P019 4SE, United Kingdom

Location

Walsgrave Hospital

Coventry, England, CV2 2DX, United Kingdom

Location

Mayday University Hospital

Croydon, England, United Kingdom

Location

Derbyshire Royal Infirmary

Derby, England, DE1 2QY, United Kingdom

Location

Doncaster Royal Infirmary

Doncaster, England, DN2 5LT, United Kingdom

Location

Dorset County Hospital

Dorchester, England, DT1 2JY, United Kingdom

Location

Russells Hall Hospital

Dudley, England, DY1 2HQ, United Kingdom

Location

Royal Devon and Exeter Hospital

Exeter, England, EX2 5DW, United Kingdom

Location

Medway Maritime Hospital

Gillingham Kent, England, ME7 5NY, United Kingdom

Location

Harrogate District Hospital

Harrogate, England, HG2 7SX, United Kingdom

Location

Northwick Park Hospital

Harrow, England, HA1 3UJ, United Kingdom

Location

Hemel Hempstead General

Hemel Hempstead, England, HP2 4AD, United Kingdom

Location

Wycombe General Hospital

High Wycombe, England, United Kingdom

Location

Hull Royal Infirmary

Hull, England, HU3 2KZ, United Kingdom

Location

Ipswich Hospital

Ipswich, England, IP4 5PD, United Kingdom

Location

West Middlesex University Hospital

Isleworth, England, TW7 6AF, United Kingdom

Location

Kettering General Hosptial

Kettering, Northants, England, NNI6 8UZ, United Kingdom

Location

Kidderminster Hospital

Kidderminster Worcestershire, England, DY11 6RJ, United Kingdom

Location

Crosshouse Hospital

Kilmarnock, England, KA2 OBE, United Kingdom

Location

Leeds General Infirmary

Leeds, England, LS1 3EX, United Kingdom

Location

Leicester Royal Infirmary

Leicester, England, LE1 5WW, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, England, L7 8XP, United Kingdom

Location

Aintree University Hospital

Liverpool, England, L9 7AL, United Kingdom

Location

Saint Bartholomew's Hospital

London, England, EC1A 7BE, United Kingdom

Location

UCL Cancer Institute

London, England, NW1 2QG, United Kingdom

Location

University Hospital Lewisham

London, England, SE13 6LH, United Kingdom

Location

Queen Elizabeth Hospital - Woolwich

London, England, SE18 4QH, United Kingdom

Location

King's College Hospital

London, England, SE5 8RX, United Kingdom

Location

St. George's Hospital

London, England, SW17 0QT, United Kingdom

Location

University College Hospital - London

London, England, WC1E 6AU, United Kingdom

Location

Maidstone Hospital

Maidstone, England, ME16 9QQ, United Kingdom

Location

Manchester Royal Infirmary

Manchester, England, M13 9WL, United Kingdom

Location

Christie Hospital

Manchester, England, M20 4BX, United Kingdom

Location

Trafford General Hospital

Manchester, England, M31 3SL, United Kingdom

Location

Borders General Hospital

Melrose, England, TD6 9BS, United Kingdom

Location

Arrowe Park Hospital

Metropolitan Borough of Wirral, England, CH49 5PE, United Kingdom

Location

James Paget Hospital

Norfolk, England, NR31 6LA, United Kingdom

Location

Nottingham City Hospital

Nottingham, England, NG5 1PB, United Kingdom

Location

Derriford Hospital

Plymouth, England, PL6 8DH, United Kingdom

Location

Whiston Hospital

Prescot Merseyside, England, L35 5DR, United Kingdom

Location

Berkshire Cancer Centre at Royal Berkshire Hospital

Reading, England, RG1 5AN, United Kingdom

Location

Conquest Hospital

Saint Leonards-on-Sea, England, TN37 7RD, United Kingdom

Location

Hope Hospital

Salford, England, M6 8HD, United Kingdom

Location

Salisbury District Hospital

Salisbury, England, SP2 8BJ, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, England, S1O 2JF, United Kingdom

Location

Southampton General Hospital

Southampton, England, SO16 6YD, United Kingdom

Location

Southport and Formby District General Hospital

Southport, England, PR8 6PN, United Kingdom

Location

Staffordshire General Hospital

Stafford, England, ST16 3SA, United Kingdom

Location

Sunderland Royal Hospital

Sunderland, England, SR4 7TP, United Kingdom

Location

Royal Marsden - Surrey

Sutton, England, SM2 5PT, United Kingdom

Location

Great Western Hospital

Swindon, England, SN3 6BB, United Kingdom

Location

Taunton and Somerset Hospital

Taunton Somerset, England, TA1 5DA, United Kingdom

Location

Torbay Hospital

Torquay, England, TQ2 7AA, United Kingdom

Location

Royal Cornwall Hospital

Truro, Cornwall, England, TR1 3LJ, United Kingdom

Location

Hillingdon Hospital

Uxbridge, England, UB8 3NN, United Kingdom

Location

Sandwell General Hospital

West Bromwich, England, B71 4HJ, United Kingdom

Location

Worcester Royal Hospital

Worcester, England, WR5 1DD, United Kingdom

Location

Worthing Hospital

Worthing, England, BN11 2DH, United Kingdom

Location

Cancer Care Center

York, England, Y031 8HE, United Kingdom

Location

Aberdeen Royal Infirmary

Aberdeen, Scotland, AB25 2ZN, United Kingdom

Location

Monklands General Hospital

Airdrie, Scotland, ML6 0JF, United Kingdom

Location

Ninewells Hospital

Dundee, Scotland, DD1 9SY, United Kingdom

Location

Edinburgh Cancer Centre at Western General Hospital

Edinburgh, Scotland, EH4 2XU, United Kingdom

Location

Falkirk and District Royal Infirmary

Falkirk, Scotland, FK1 5QE, United Kingdom

Location

Western Infirmary

Glasgow, Scotland, G11 6NT, United Kingdom

Location

Royal Infirmary - Castle

Glasgow, Scotland, G4 0SF, United Kingdom

Location

Victoria Infirmary

Glasgow, Scotland, G42 9TY, United Kingdom

Location

Southern General Hospital

Glasgow, Scotland, G51 4TF, United Kingdom

Location

Raigmore Hospital

Inverness, Scotland, 1V2 3UJ, United Kingdom

Location

Victoria Hospital

Kirkcaldy, Scotland, KY2 5AH, United Kingdom

Location

Royal Alexandra Hospital

Paisley, Scotland, United Kingdom

Location

Dorset Cancer Centre

Wakefield, Scotland, WF1 4DG, United Kingdom

Location

Pinderfields General Hospital

Wakefield, Scotland, WF1 4DG, United Kingdom

Location

Ysbyty Gwynedd

Bangor, Wales, LL57 2PW, United Kingdom

Location

University Hospital of Wales

Cardiff, Wales, CF14 4XW, United Kingdom

Location

Glan Clwyd Hospital

Rhyl, Denbighshire, Wales, LL 18 5UJ, United Kingdom

Location

South West Wales Cancer Institute

Swansea, Wales, SA2 8QA, United Kingdom

Location

Hereford Hospitals

Hereford, HR1 2ER, United Kingdom

Location

Wexham Park Hospital

Slough, Berkshire, SL2 4HL, United Kingdom

Location

Kingston Hospital

Surrey, KT2 7QB, United Kingdom

Location

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Anemia, Refractory, with Excess of Blasts; Leukemia, Basophilic, Acute; Leukemia, Eosinophilic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Leukemia, Erythroblastic, Acute; Congenital Abnormalities; Leukemia, Myelomonocytic, Acute

Interventions

Alemtuzumab; Arsenic Trioxide; Azacitidine; Busulfan; Clofarabine; Cytarabine; Daunorubicin; fludarabine phosphate; Gemtuzumab; Melphalan; tipifarnib; DNA Methylation; Cytogenetic Analysis; Gene Expression Profiling; Immunologic Techniques

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Anemia, Refractory; Anemia; Leukemia, Myeloid; Myeloproliferative Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Arsenicals; Inorganic Chemicals; Oxides; Oxygen Compounds; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Arabinonucleosides; Nucleotides; Ribonucleotides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Calicheamicins; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Methylation; Alkylation; Biochemical Phenomena; Chemical Phenomena; Metabolism; Genetic Phenomena; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques

Study Officials

• Alan K. Burnett, MD, FRCP

  University Hospital of Wales

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 27, 2007
• First Posted: March 30, 2007
• Study Start: August 1, 2006
• Primary Completion: August 1, 2012
• Last Updated: August 26, 2013

Record last verified: 2008-08

Locations

GB (96)