Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

Leukemia Clinical Trial

— AML-19  

Official title:

Gemtuzumab Ozogamicin (GO) Monotherapy Versus Standard Supportive Care for Previously Untreated AML in Elderly Patients Who Are Not Eligible for Intensive Chemotherapy: A Randomized Phase II/III Trial (AML-19) of the EORTC-LG and GIMEMA-ALWP

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00091234
• Other study ID #: EORTC-06031
• Secondary ID: EORTC-06031
• Status: Recruiting
• Phase: Phase 2/Phase 3
• First received: September 7, 2004
• Last updated: July 23, 2012
• Start date: June 2004

Study information

• Verified date: July 2012
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: Hilde Breyssens
• Email: hilde.breyssens[@]eortc.be
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)Belgium: Federal Agency for Medicinal Products and Health ProductsItaly: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Monoclonal antibodies such as gemtuzumab ozogamicin can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. It is not yet known whether gemtuzumab ozogamicin is more effective than standard supportive care in treating older patients who have acute myeloid leukemia.

PURPOSE: This randomized phase II/III trial is studying two different gemtuzumab ozogamicin regimens to see how well they work compared to standard supportive care in treating older patients with previously untreated acute myeloid leukemia.

Description:

OBJECTIVES:

• Compare the feasibility, toxicity, and antileukemic activity of two different dosing regimens of gemtuzumab ozogamicin (GO) vs standard supportive care in older patients with previously untreated acute myeloid leukemia who are not candidates for intensive chemotherapy. (phase II)

• Compare the efficacy and toxicity of the best dosing regimen of GO selected from phase II vs standard supportive care, in terms of overall survival, in these patients. (phase III)

OUTLINE: This is a randomized, open-label, multicenter phase II study followed by a phase III study. Patients are stratified according to age (61 to 75 vs 76 to 80 vs 81 and over), CD33-positivity of bone marrow blasts (< 20% vs 20-80% vs > 80% vs unknown), initial WBC before hydroxyurea administration (< 30,000/mm^3 vs ≥ 30,000/mm^3), WHO performance status (0-1 vs 2 vs 3-4), and participating center.

• Phase II: Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients receive gemtuzumab ozogamicin (GO) IV over 2 hours on days 1 and

8. Patients with stable or responding disease at day 36 receive GO IV over 2 hours every 4 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients receive GO IV over 2 hours on days 1, 3, and 5. Patients with stable or responding disease at day 36 receive GO IV over 2 hours every 4 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity.

• Arm III: Patients receive standard supportive care.

• Phase III: Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive the selected treatment (arm I or arm II) from phase II.

• Arm II: Patients receive standard supportive care. Patients who receive GO treatment are followed monthly for 1 year and then every 3 months thereafter. Patients who receive standard supportive care are followed at least every 4 weeks.

PROJECTED ACCRUAL: A total of 259 patients (75 for phase II [25 per treatment arm] and 184 for phase III [92 per treatment arm]) will be accrued for this study within 2.5 years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 279
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 61 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed acute myeloid leukemia (AML)

• At least 20% bone marrow blasts by bone marrow aspiration or biopsy

• All subtypes except M3 (acute promyelocytic leukemia) are allowed

• Previously untreated primary or secondary disease (including AML after myelodysplastic syndromes)

• Ineligible for intensive chemotherapy, as defined by 1 of the following criteria:

• 61 to 75 years old AND WHO performance status > 2 AND/OR unwilling to receive intensive chemotherapy

• Over 75 years old

• No blast crisis of chronic myeloid leukemia

• No AML supervention after other myeloproliferative disease

• WBC < 30,000/mm^3 and meets 1 of the following criteria:

• WBC < 30,000/mm^3 at diagnosis AND had no prior treatment with hydroxyurea

• WBC = 30,000/mm^3 at diagnosis AND received mandatory pretreatment with hydroxyurea (up to 14 days duration) until WBC < 30,000/mm^3

• No active CNS leukemia

PATIENT CHARACTERISTICS:

Age

• See Disease Characteristics

• 61 and over

Performance status

• See Disease Characteristics

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• Bilirubin = 1.5 times upper limit of normal (ULN)

Renal

• Creatinine = 1.5 times ULN

Cardiovascular

• No arrhythmia requiring chronic treatment

• No congestive heart failure

• No symptomatic ischemic heart disease

• No other severe cardiovascular disease

Pulmonary

• No severe pulmonary dysfunction = grade 3

Other

• No alcohol abuse

• No severe neurological or psychiatric disease

• No active uncontrolled infection or severe systemic infection

• No other malignancy

• No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up

• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)

• No concurrent antiangiogenic drugs

Chemotherapy

• See Disease Characteristics

• Concurrent low-dose cytostatic agents (i.e., thioguanine or mercaptopurine) allowed for palliative care (standard supportive care arm only)

Endocrine therapy

• Prior corticosteroids (duration = 14 days ) for primary or secondary AML allowed

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No other concurrent cytotoxic drugs

• No other concurrent experimental therapy

• No concurrent tyrosine kinase inhibitors

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid, Acute

Intervention

Drug:
• gemtuzumab ozogamicin

Locations

Country	Name	City	State
Belgium	Ziekenhuis Netwerk Antwerpen Middelheim	Antwerp
Belgium	AZ Sint-Jan	Brugge
Belgium	Hopital Universitaire Erasme	Brussels
Belgium	Institut Jules Bordet	Brussels
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	CHU Liege - Domaine Universitaire du Sart Tilman	Liege
Belgium	Centre Hospitalier Peltzer-La Tourelle	Verviers
Italy	Ospedale S Donato, USL-8	Arezzo cap
Italy	Universita Degli Studi di Bari	Bari
Italy	Universita Di Brescia	Brescia
Italy	Ospedale Binaghi	Cagliari
Italy	Ospedale Oncologico A. Businco	Cagliari
Italy	Ospedale Regionale A Pugliese	Cantanzaro
Italy	Ospedale Ferrarotto	Catania
Italy	Ospedale Regionale A. Pugliese	Catanzaro
Italy	Universita di Ferrara	Ferrara
Italy	Azienda Ospedaliera Vito Fazzi	Lecce
Italy	Azienda Ospedaliera - Universitaria di Modena	Modena
Italy	Ospedale Di Montefiascone	Montefiascone
Italy	Azienda Ospedaliera di Rilievo Nazionale A.Cardarelli	Naples
Italy	Ospedale Maggiore della Carita	Novara
Italy	Azienda Ospedaliera Policlinico Paolo Giaccone	Palermo
Italy	Ospedale La Maddalena - Palermo	Palermo
Italy	Azienda Ospedaliera Di Parma	Parma
Italy	Policlinico Monteluce	Perugia
Italy	Ospedale San Salvatore	Pesaro
Italy	Ospedale Civile Pescara	Pescara
Italy	Ospedale San Carlo	Potenza
Italy	Ospedale Sta. Maria Delle Croci	Ravenna
Italy	Ospedale Sant'Andrea	Roma
Italy	Azienda Ospedaliera Universitaria Policlinico Tor Vergata	Rome
Italy	Azienda Policlinico Umberto Primo	Rome
Italy	H. San Giovanni-Addolorata Hospital	Rome
Italy	Istituto Regina Elena	Rome
Italy	Libero Istituto Universitario Campus Bio-Medico	Rome
Italy	Ospedale Sant' Eugenio	Rome
Italy	Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore	Rome
Italy	Universita Degli Studi "La Sapeinza"	Rome
Italy	Istituto di Ematologia Universita - University di Sassari	Sassari
Italy	Universita di Siena	Siena
Italy	Ospedale Maggiore dell' Universita	Trieste
Netherlands	Jeroen Bosch Ziekenhuis	's-Hertogenbosch
Netherlands	Onze Lieve Vrouwe Gasthuis	Amsterdam
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Universitair Medisch Centrum St. Radboud - Nijmegen	Nijmegen

Sponsors (2)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC	Gruppo Italiano Malattie EMatologiche dell'Adulto

Countries where clinical trial is conducted

Belgium,  Italy,  Netherlands, 

References & Publications (1)

Amadori S, Suciu S, Selleslag D, Aversa F, Gaidano G, Musso M, Annino L, Venditti A, Voso MT, Mazzone C, Magro D, De Fabritiis P, Muus P, Alimena G, Mancini M, Hagemeijer A, Paoloni F, Vignetti M, Fazi P, Meert L, Ramadan SM, Willemze R, de Witte T, Baron — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients able to start continuation therapy (Phase II)			No
Primary	Overall survival (Phase III)
Secondary	Rate of complete remission (CR+CRp)by the end of continuation therapy, for patients in the GO arms (Phase II)			No
Secondary	Overall survival (Phase II)			No
Secondary	Toxicity (CTCAE grading), including time to hematological recovery (Phase II & III)			No
Secondary	Rate of complete remisison (CR+CRp) by the end of induction and by the end of continuation therapy, for patients in GO arm (Phase III)			Yes
Secondary	Disease-free survival for patients who reached CR or CRp (Phase III)
Secondary	Progression-free survival from randomization for patients in GO arm (Phase III)