AML-19: Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC (Other)

Overall Status

Unknown status

CT.gov ID

NCT00091234

Collaborator

Gruppo Italiano Malattie EMatologiche dell'Adulto (Other)

279

Enrollment

Locations

6.2

Patients Per Site

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: gemtuzumab ozogamicin	Phase 2/Phase 3

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

279 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Jun 1, 2004

Anticipated Primary Completion Date :

Dec 1, 2013

Outcome Measures

Primary Outcome Measures

Proportion of patients able to start continuation therapy (Phase II) []
Overall survival (Phase III) []

Secondary Outcome Measures

Rate of complete remission (CR+CRp)by the end of continuation therapy, for patients in the GO arms (Phase II) []
Overall survival (Phase II) []
Toxicity (CTCAE grading), including time to hematological recovery (Phase II & III) []
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) []
Disease-free survival for patients who reached CR or CRp (Phase III) []
Progression-free survival from randomization for patients in GO arm (Phase III) []

Eligibility Criteria

Criteria

Ages Eligible for Study:

61 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Ziekenhuis Netwerk Antwerpen Middelheim	Antwerp	Belgium	2020
2	AZ Sint-Jan	Brugge	Belgium	8000
3	Institut Jules Bordet	Brussels	Belgium	1000
4	Hopital Universitaire Erasme	Brussels	Belgium	1070
5	Universitair Ziekenhuis Antwerpen	Edegem	Belgium	B-2650
6	CHU Liege - Domaine Universitaire du Sart Tilman	Liege	Belgium	B-4000
7	Centre Hospitalier Peltzer-La Tourelle	Verviers	Belgium	B-4800
8	Ospedale S Donato, USL-8	Arezzo cap	Italy
9	Universita Degli Studi di Bari	Bari	Italy	70124
10	Universita Di Brescia	Brescia	Italy
11	Ospedale Binaghi	Cagliari	Italy	090100
12	Ospedale Oncologico A. Businco	Cagliari	Italy	09121
13	Ospedale Regionale A Pugliese	Cantanzaro	Italy
14	Ospedale Ferrarotto	Catania	Italy	95124
15	Ospedale Regionale A. Pugliese	Catanzaro	Italy	88100
16	Universita di Ferrara	Ferrara	Italy	44100
17	Azienda Ospedaliera Vito Fazzi	Lecce	Italy	73100
18	Azienda Ospedaliera - Universitaria di Modena	Modena	Italy	41100
19	Ospedale Di Montefiascone	Montefiascone	Italy	I-01027
20	Azienda Ospedaliera di Rilievo Nazionale A.Cardarelli	Naples	Italy	80127
21	Ospedale Maggiore della Carita	Novara	Italy
22	Azienda Ospedaliera Policlinico Paolo Giaccone	Palermo	Italy	90127
23	Ospedale La Maddalena - Palermo	Palermo	Italy
24	Azienda Ospedaliera Di Parma	Parma	Italy	43100
25	Policlinico Monteluce	Perugia	Italy	06122
26	Ospedale San Salvatore	Pesaro	Italy	I-61100
27	Ospedale Civile Pescara	Pescara	Italy	65100
28	Ospedale San Carlo	Potenza	Italy
29	Ospedale Sta. Maria Delle Croci	Ravenna	Italy	48100
30	Ospedale Sant'Andrea	Roma	Italy
31	Azienda Ospedaliera Universitaria Policlinico Tor Vergata	Rome	Italy	00133
32	Ospedale Sant' Eugenio	Rome	Italy	00144
33	Libero Istituto Universitario Campus Bio-Medico	Rome	Italy	00155
34	Azienda Policlinico Umberto Primo	Rome	Italy	00161
35	Istituto Regina Elena	Rome	Italy	00161
36	Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore	Rome	Italy	00168
37	H. San Giovanni-Addolorata Hospital	Rome	Italy	00184
38	Universita Degli Studi "La Sapeinza"	Rome	Italy
39	Istituto di Ematologia Universita - University di Sassari	Sassari	Italy	07100
40	Universita di Siena	Siena	Italy	53100
41	Ospedale Maggiore dell' Universita	Trieste	Italy	34100
42	Jeroen Bosch Ziekenhuis	's-Hertogenbosch	Netherlands	5211 NL
43	Onze Lieve Vrouwe Gasthuis	Amsterdam	Netherlands	1091 HA
44	Leiden University Medical Center	Leiden	Netherlands	2300 RC
45	Universitair Medisch Centrum St. Radboud - Nijmegen	Nijmegen	Netherlands	NL-6500 HB

Sponsors and Collaborators

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

Investigators

Principal Investigator: Sergio Amadori, MD, EORTC - AZIENDA OSPEDALLERA UNIVERSITARIA - POLICLINICO TOR VERGATA, IT
Principal Investigator: Giuliana Alimena, GIMEMA - Universita Degli Studi "La Sapeinza"