Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia
Conditions
Leukemia
Conditions: official terms
Leukemia - Leukemia, Myeloid, Acute
Conditions: Keywords
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), untreated adult acute myeloid leukemia, secondary acute myeloid leukemia, adult acute basophilic leukemia, adult acute eosinophilic leukemia, adult erythroleukemia (M6a), adult pure erythroid leukemia (M6b), 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 acute myelomonocytic leukemia (M4)
Study Type
Interventional
Study Phase
Phase 2/Phase 3
Study Design
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: gemtuzumab ozogamicin
Type: Drug
Overall Status
Recruiting
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.
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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 61 Years
Gender: Both
Criteria: 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
Locations
Ziekenhuis Netwerk Antwerpen Middelheim
Antwerp, Belgium
Status: Recruiting
Contact: Contact Person - 32-3-280-3111
AZ Sint-Jan
Brugge, Belgium
Status: Recruiting
Contact: Contact Person - 32-50-45-2111
Hopital Universitaire Erasme
Brussels, Belgium
Status: Recruiting
Contact: Contact Person - 32-2-555-3806
Institut Jules Bordet
Brussels, Belgium
Status: Recruiting
Contact: Contact Person - 32-2-541-3510
Universitair Ziekenhuis Antwerpen
Edegem, Belgium
Status: Recruiting
Contact: Contact Person - 32-03-821-3375
CHU Liege - Domaine Universitaire du Sart Tilman
Liege, Belgium
Status: Recruiting
Contact: Contact Person - 32-4-366-7111
Centre Hospitalier Peltzer-La Tourelle
Verviers, Belgium
Status: Recruiting
Contact: Contact Person - 328-721-2111
Ospedale S Donato, USL-8
Arezzo cap, Italy
Status: Recruiting
Universita Degli Studi di Bari
Bari, Italy
Status: Recruiting
Contact: Contact Person - 39-080-547-8660
Universita Di Brescia
Brescia, Italy
Status: Recruiting
Ospedale Binaghi
Cagliari, Italy
Status: Recruiting
Contact: Contact Person - 39-070-609-3149
Ospedale Oncologico A. Businco
Cagliari, Italy
Status: Recruiting
Contact: Contact Person - 39-070-609-5204
Ospedale Regionale A Pugliese
Cantanzaro, Italy
Status: Recruiting
Ospedale Ferrarotto
Catania, Italy
Status: Recruiting
Contact: Contact Person - 39-095-743-5915
Ospedale Regionale A. Pugliese
Catanzaro, Italy
Status: Recruiting
Contact: Contact Person - 39-961-883-346
Universita di Ferrara
Ferrara, Italy
Status: Recruiting
Contact: Contact Person - 39-532-209-100
Azienda Ospedaliera Vito Fazzi
Lecce, Italy
Status: Recruiting
Contact: Contact Person - 39-083-266-1235
Azienda Ospedaliera - Universitaria di Modena
Modena, Italy
Status: Recruiting
Contact: Contact Person - 39-059-422-4373
Ospedale Di Montefiascone
Montefiascone, Italy
Status: Recruiting
Contact: Contact Person - 39-07-618-331
Azienda Ospedaliera di Rilievo Nazionale A.Cardarelli
Naples, Italy
Status: Recruiting
Contact: Contact Person - 39-081-747-3011
Ospedale Maggiore della Carita
Novara, Italy
Status: Recruiting
Azienda Ospedaliera Policlinico Paolo Giaccone
Palermo, Italy
Status: Recruiting
Contact: Contact Person - 39-091-655-2321
Ospedale La Maddalena - Palermo
Palermo, Italy
Status: Recruiting
Contact: Contact Person - 39-91-680-6111
Azienda Ospedaliera Di Parma
Parma, Italy
Status: Recruiting
Contact: Contact Person - 39-0521-702-441
Policlinico Monteluce
Perugia, Italy
Status: Recruiting
Contact: Massimo F. Martelli, MD - 39-75-5783219 - ematol@unipg.it
Ospedale San Salvatore
Pesaro, Italy
Status: Recruiting
Contact: G. Lucarelli - 0039-0721-36424
Ospedale Civile Pescara
Pescara, Italy
Status: Recruiting
Contact: Contact Person
Ospedale San Carlo
Potenza, Italy
Status: Recruiting
Ospedale Sta. Maria Delle Croci
Ravenna, Italy
Status: Recruiting
Contact: Contact Person - 39-544-285-247
Ospedale Sant'Andrea
Roma, Italy
Status: Recruiting
Azienda Ospedaliera Universitaria Policlinico Tor Vergata
Rome, Italy
Status: Recruiting
Contact: Contact Person - 39-06-20-901
Azienda Policlinico Umberto Primo
Rome, Italy
Status: Recruiting
Contact: Franco Mandelli - 39-06-85-79-51
H. San Giovanni-Addolorata Hospital
Rome, Italy
Status: Recruiting
Contact: Contact Person
Istituto Regina Elena
Rome, Italy
Status: Recruiting
Contact: Contact Person - 39-06-4985-2201
Libero Istituto Universitario Campus Bio-Medico
Rome, Italy
Status: Recruiting
Contact: Contact - 39-06-2254-1366
Ospedale Sant' Eugenio
Rome, Italy
Status: Recruiting
Contact: Contact Person - 39-06-5100-2569
Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore
Rome, Italy
Status: Recruiting
Contact: Contact Person - 39-06-3015-5556
Universita Degli Studi "La Sapeinza"
Rome, Italy
Status: Recruiting
Contact: Giuliana Alimena - 39-06-857-951
Istituto di Ematologia Universita - University di Sassari
Sassari, Italy
Status: Recruiting
Contact: Contact Person - 39-79-228-280
Universita di Siena
Siena, Italy
Status: Recruiting
Contact: Contact Person - 39-0577-586-429
Ospedale Maggiore dell' Universita
Trieste, Italy
Status: Recruiting
Contact: Contact Person - 39-040-399-2232
Jeroen Bosch Ziekenhuis
's-Hertogenbosch, Netherlands
Status: Recruiting
Contact: Contact Person - 31-73-699-2000
Onze Lieve Vrouwe Gasthuis
Amsterdam, Netherlands
Status: Recruiting
Contact: Contact Person - 31-20-599-9111
Leiden University Medical Center
Leiden, Netherlands
Status: Recruiting
Contact: Contact Person - 31-71-526-9111
Universitair Medisch Centrum St. Radboud - Nijmegen
Nijmegen, Netherlands
Status: Recruiting
Contact: Contact Person
Start Date
June 2004
Sponsors
European Organisation for Research and Treatment of Cancer - EORTC
Source
European Organisation for Research and Treatment of Cancer - EORTC
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page