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

Sponsor

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

Overall Status

Completed

CT.gov ID

NCT00006122

Collaborator

(none)

106

Enrollment

Locations

5.9

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. 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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: cytarabine Drug: etoposide Drug: gemtuzumab ozogamicin Drug: idarubicin Drug: mitoxantrone hydrochloride	Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

106 participants

Primary Purpose:

Treatment

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

Study Start Date :

Jun 1, 2000

Actual Primary Completion Date :

Jan 1, 2002

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

61 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Innsbruck Universitaetsklinik	Innsbruck	Austria	A-6020
2	A.Z. St. Jan	Brugge	Belgium	8000
3	Universitair Ziekenhuis Antwerpen	Edegem	Belgium	B-2650
4	CHU Sart-Tilman	Liege	Belgium	B-4000
5	University Hospital Rebro	Zagreb	Croatia	41000
6	Hopital Edouard Herriot	Lyon	France	69437
7	Hotel Dieu de Paris	Paris	France	75181
8	Hopital Necker	Paris	France	75743
9	Medizinische Klinik und Poliklinik	Heidelberg	Germany	D-69115
10	Eberhard Karls Universitaet	Tuebingen	Germany	D-72076
11	Ospedale Generale Regionale	Bolzano	Italy	39100
12	Ospedali Riuniti	Reggio Calabria	Italy	89100
13	Ospedale San Eugenio	Rome	Italy	00144
14	Azienda Policlinico Umberto Primo	Rome	Italy	00161
15	Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore	Rome	Italy	00168
16	Groot Ziekengasthuis 's-Hertogenbosch	's-Hertogenbosch	Netherlands	5211 NL
17	Leiden University Medical Center	Leiden	Netherlands	2300 CA
18	University Medical Center Nijmegen	Nijmegen	Netherlands	NL-6500 HB