Clinical trial NCT00091234: Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Leukemia
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)
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
Collaborators: name: Gruppo Italiano Malattie EMatologiche dell'Adulto
First posted: 2004-09-09
Enrollment: 279
Sex: ALL
Minimum age (years): 61
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Proportion of patients able to start continuation therapy (Phase II)
measure: Overall survival (Phase III)
Secondary outcomes:
measure: Rate of complete remission (CR+CRp)by the end of continuation therapy, for patients in the GO arms (Phase II)
measure: Overall survival (Phase II)
measure: Toxicity (CTCAE grading), including time to hematological recovery (Phase II & III)
measure: 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)
measure: Disease-free survival for patients who reached CR or CRp (Phase III)
measure: Progression-free survival from randomization for patients in GO arm (Phase III)
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: Ziekenhuis Netwerk Antwerpen Middelheim
city: Brugge
country: Belgium
facility: AZ Sint-Jan
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Brussels
country: Belgium
facility: Hopital Universitaire Erasme
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Liege
country: Belgium
facility: CHU Liege - Domaine Universitaire du Sart Tilman
city: Verviers
country: Belgium
facility: Centre Hospitalier Peltzer-La Tourelle
city: Arezzo cap
country: Italy
facility: Ospedale S Donato, USL-8
city: Bari
country: Italy
facility: Universita Degli Studi di Bari
city: Brescia
country: Italy
facility: Universita Di Brescia
city: Cagliari
country: Italy
facility: Ospedale Binaghi
city: Cagliari
country: Italy
facility: Ospedale Oncologico A. Businco
city: Cantanzaro
country: Italy
facility: Ospedale Regionale A Pugliese
city: Catania
country: Italy
facility: Ospedale Ferrarotto
city: Catanzaro
country: Italy
facility: Ospedale Regionale A. Pugliese
city: Ferrara
country: Italy
facility: Universita di Ferrara
city: Lecce
country: Italy
facility: Azienda Ospedaliera Vito Fazzi
city: Modena
country: Italy
facility: Azienda Ospedaliera - Universitaria di Modena
city: Montefiascone
country: Italy
facility: Ospedale Di Montefiascone
city: Naples
country: Italy
facility: Azienda Ospedaliera di Rilievo Nazionale A.Cardarelli
city: Novara
country: Italy
facility: Ospedale Maggiore della Carita
city: Palermo
country: Italy
facility: Azienda Ospedaliera Policlinico Paolo Giaccone
city: Palermo
country: Italy
facility: Ospedale La Maddalena - Palermo
city: Parma
country: Italy
facility: Azienda Ospedaliera Di Parma
city: Perugia
country: Italy
facility: Policlinico Monteluce
city: Pesaro
country: Italy
facility: Ospedale San Salvatore
city: Pescara
country: Italy
facility: Ospedale Civile Pescara
city: Potenza
country: Italy
facility: Ospedale San Carlo
city: Ravenna
country: Italy
facility: Ospedale Sta. Maria Delle Croci
city: Roma
country: Italy
facility: Ospedale Sant'Andrea
city: Rome
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Tor Vergata
city: Rome
country: Italy
facility: Ospedale Sant' Eugenio
city: Rome
country: Italy
facility: Libero Istituto Universitario Campus Bio-Medico
city: Rome
country: Italy
facility: Azienda Policlinico Umberto Primo
city: Rome
country: Italy
facility: Istituto Regina Elena
city: Rome
country: Italy
facility: Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore
city: Rome
country: Italy
facility: H. San Giovanni-Addolorata Hospital
city: Rome
country: Italy
facility: Universita Degli Studi "La Sapeinza"
city: Sassari
country: Italy
facility: Istituto di Ematologia Universita - University di Sassari
city: Siena
country: Italy
facility: Universita di Siena
city: Trieste
country: Italy
facility: Ospedale Maggiore dell' Universita
city: 's-Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Nijmegen
country: Netherlands
facility: Universitair Medisch Centrum St. Radboud - Nijmegen
Study officials:
affiliation: EORTC - AZIENDA OSPEDALLERA UNIVERSITARIA - POLICLINICO TOR VERGATA, IT
name: Sergio Amadori, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: GIMEMA - Universita Degli Studi "La Sapeinza"
name: Giuliana Alimena
role: PRINCIPAL_INVESTIGATOR
References:
citation: Amadori S, Suciu S, Selleslag D, et al.: Phase II-III study of gemtuzumab ozogamicin monotherapy versus best supportive care in older patients with newly diagnosed AML unfit for intensive chemotherapy: first results of the EORTC-GIMEMA AML-19 trial. [Abstract] Blood 112 (11): A-762, 2008.
citation: 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 F. Gemtuzumab Ozogamicin Versus Best Supportive Care in Older Patients With Newly Diagnosed Acute Myeloid Leukemia Unsuitable for Intensive Chemotherapy: Results of the Randomized Phase III EORTC-GIMEMA AML-19 Trial. J Clin Oncol. 2016 Mar 20;34(9):972-9. doi: 10.1200/JCO.2015.64.0060. Epub 2016 Jan 25.