Gemtuzumab Ozogamicin With or Without Chemotherapy in Treating Older Patients With Acute Myeloid Leukemia

Leukemia Clinical Trial

Official title:

Gemtuzumab Ozogamicin (CMA-676) Followed or Not by Intensive Chemotherapy as Initial Treatment for Elderly Patients With Acute Myeloid Leukemia: An EORTC-LG Pilot Phase II Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006122
• Other study ID #: EORTC-06993
• Secondary ID: EORTC-06993-AML-
• Status: Completed
• Phase: Phase 2
• First received: August 3, 2000
• Last updated: July 13, 2012
• Start date: June 2000

Study information

• Verified date: July 2012
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• 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. Drugs used in chemotherapy uses different ways to stop cancer cells from dividing so they stop growing or die. Combining gemtuzumab ozogamicin with chemotherapy may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of gemtuzumab ozogamicin with or without chemotherapy in treating older patients who have acute myeloid leukemia.

Description:

OBJECTIVES: I. Determine the feasibility, toxicity, and antileukemic activity of gemtuzumab ozogamicin (CMA-676) with or without mitoxantrone, etoposide, cytarabine, and idarubicin in elderly patients with acute myeloid leukemia.

OUTLINE: This is a multicenter study. Patients are stratified according to risk (standard risk, defined as age 61-75 and WHO performance status 0-1 vs poor risk, defined as over 75 years and WHO performance status 0-2 OR under 76 years and WHO performance status 2). Frontline therapy: Patients receive gemtuzumab ozogamicin IV over 2 hours on days 1 and 15. Stratum I (Standard risk patients): Patients with disease progression at any time during frontline therapy may begin induction therapy immediately. Induction therapy begins 7-10 days after response assessment regardless of response and in the absence of unacceptable toxicity. Stratum II (Poor risk patients): Patients experiencing complete remission with or without platelet recovery will begin consolidation therapy within 4-8 weeks of response assessment in the absence of unacceptable toxicity. Stratum I Induction therapy: Patients receive mitoxantrone IV over 30 minutes on days 1, 3 and 5; etoposide IV over 1 hour on days 1-3; and cytarabine IV continuously on days 1-7. Patients experiencing partial response are given a second induction therapy course. Patients experiencing complete remission with or without platelet recovery after 1 or 2 induction courses begin consolidation therapy within 4-8 weeks of response assessment in the absence of unacceptable toxicity. Consolidation therapy: Patients receive idarubicin IV on days 1, 3 and 5; etoposide IV over 1 hour on days 1-3; and cytarabine IV continuously on days 1-5. Stratum II Consolidation therapy: Patients receive gemtuzumab ozogamicin IV over 2 hours on day 1 and then 1-3 months later. Patients are followed monthly for 1 year, every 3 months for 2 years, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 45-82 (28-49 for stratum I, and 17-33 for stratum II) patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 106
• Est. primary completion date: January 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 61 Years and older

Eligibility

DISEASE CHARACTERISTICS: Diagnosis of primary or secondary acute myeloid leukemia (AML) Previously untreated At least 20% marrow blasts AML after myelodysplastic syndrome allowed No leukemia after other myeloproliferative diseases No acute promyelocytic leukemia (M3) or blastic phase chronic myelogenous leukemia No active CNS leukemia

PATIENT CHARACTERISTICS: Age: 61 and over Performance status: WHO 0-2 Life expectancy: Not specified Hematopoietic: See Disease Characteristics White blood count no greater than 30,000/mm3 unless reducible to less than 30,000/mm3 by a maximum of 7 days of hydroxyurea Hepatic: Bilirubin no greater than 3 times upper limit of normal (ULN) Renal: Creatinine no greater than 3 times ULN Cardiovascular: No severe heart failure that would preclude study Pulmonary: No severe lung failure that would preclude study Other: No other concurrent malignancies No active uncontrolled infection No concurrent severe neurological or psychiatric disease No psychological, familial, sociological or geographical condition that would preclude compliance with study HIV negative

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior humanized monoclonal antibody therapy Chemotherapy: Up to 7 days of prior hydroxyurea allowed At least 24 hours since prior hydroxyurea No other prior chemotherapy for AML Endocrine therapy: No more than 7 days of prior corticosteroids No other prior endocrine therapy Radiotherapy: No prior radiotherapy Surgery: Not specified

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• cytarabine

• etoposide

• gemtuzumab ozogamicin

• idarubicin

• mitoxantrone hydrochloride

Locations

Country	Name	City	State
Austria	Innsbruck Universitaetsklinik	Innsbruck
Belgium	A.Z. St. Jan	Brugge
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	CHU Sart-Tilman	Liege
Croatia	University Hospital Rebro	Zagreb
France	Hopital Edouard Herriot	Lyon
France	Hopital Necker	Paris
France	Hotel Dieu de Paris	Paris
Germany	Medizinische Klinik und Poliklinik	Heidelberg
Germany	Eberhard Karls Universitaet	Tuebingen
Italy	Ospedale Generale Regionale	Bolzano
Italy	Ospedali Riuniti	Reggio Calabria
Italy	Azienda Policlinico Umberto Primo	Rome
Italy	Ospedale San Eugenio	Rome
Italy	Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore	Rome
Netherlands	Groot Ziekengasthuis 's-Hertogenbosch	's-Hertogenbosch
Netherlands	Leiden University Medical Center	Leiden
Netherlands	University Medical Center Nijmegen	Nijmegen

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Austria,  Belgium,  Croatia,  France,  Germany,  Italy,  Netherlands, 

References & Publications (3)

Amadori S, Suciu S, Willemze R, et al.: Up-front window trial of gemtuzumab ozogamicin (GO) in previously untreated elderly patients with AML: an EORTC leukemia group study. [Abstract] Blood 104 (11): A-877, 2004.

Amadori S, Suciu S, Willemze R, Mandelli F, Selleslag D, Stauder R, Ho A, Denzlinger C, Leone G, Fabris P, Muus P, Vignetti M, Hagemeijer A, Beeldens F, Anak O, De Witte T; EORTC leukemia group; GIMEMA leukemia group. Sequential administration of gemtuzum — View Citation

Seedhouse CH, Grundy M, White P, Li Y, Fisher J, Yakunina D, Moorman AV, Hoy T, Russell N, Burnett A, Pallis M; National Cancer Research Network. Sequential influences of leukemia-specific and genetic factors on p-glycoprotein expression in blasts from 817 patients entered into the National Cancer Research Network acute myeloid leukemia 14 and 15 trials. Clin Cancer Res. 2007 Dec 1;13(23):7059-66. — View Citation