Oblimersen, Cytarabine, and Daunorubicin in Treating Older Patients With Acute Myeloid Leukemia
A Phase I Study of G3139 ( NSC # 683428) in Combination With Cytarabine and Daunorubicin in Previously Untreated Patients With Acute Myeloid Leukemia (AML)>= 60 Years of Age
연구 개요
상태
정황
상세 설명
OBJECTIVES:
I. Determine the maximum tolerated dose of daunorubicin in combination with cytarabine and oblimersen in older patients with previously untreated acute myeloid leukemia.
II. Determine the qualitative and quantitative toxic effects of this regimen in these patients.
III. Determine the pharmacokinetics of oblimersen in this regimen in these patients.
IV. Determine the disease-free survival and overall survival of patients treated with this regimen.
V. Assess the spontaneous rate of apoptosis in leukemic blasts in patients before and after initiation of treatment with oblimersen.
VI. Determine therapeutic response (complete remission) in patients treated with this regimen.
OUTLINE: This is a dose-escalation study of daunorubicin. Patients are stratified according to disease status (primary vs secondary).
INDUCTION THERAPY: Patients receive oblimersen (G3139) IV continuously on days 1-10 and cytarabine IV continuously on days 4-10. Patients also receive daunorubicin IV daily on days 4-6.
Patients with bone marrow cellularity of at least 20% and at least 5% leukemic blasts at day 17 or evidence of refractory disease receive a second induction comprising G3139 IV continuously on days 1-8, cytarabine IV continuously on days 4-8, and daunorubicin IV on days 4-5.
CONSOLIDATION THERAPY: Beginning no sooner than 14 days after hematologic recovery from induction therapy, patients receive G3139 IV continuously on days 1-8 and cytarabine IV over 4 hours on days 4-8. Patients receive a second course of consolidation therapy no sooner than 14 days after hematologic recovery from the first course.
Cohorts of 3-6 patients receive escalating doses of daunorubicin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Patients are followed every 2 months for 2 years.
연구 유형
등록 (실제)
단계
- 1단계
연락처 및 위치
연구 장소
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Ohio
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Columbus, Ohio, 미국, 43210
- Ohio State University Medical Center
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
Histologically confirmed primary or secondary acute myeloid leukemia (AML)
- More than 20% bone marrow blasts
- Myelodysplastic syndromes (MDS) or a chronic myeloproliferative disorder antecedent to AML allowed
- Therapy-related AML allowed
- No acute promyelocytic leukemia
- At least 4 weeks
- Bilirubin no greater than 2 mg/dL
- ALT and AST no greater than 2 times upper limit of normal (unless directly attributable to AML)
- Creatinine no greater than 2.5 mg/dL
- Ejection fraction at least 50% by MUGA or echocardiogram
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- No allergy to any of the study medications
- No other uncontrolled concurrent illness
- No serious medical or psychiatric illness that would preclude giving informed consent
- Not pregnant or nursing
- Fertile patients must use effective contraception
- No prior therapy for primary AML except emergency leukapheresis
- No prior anthracyclines
- No prior chemotherapy for primary AML except hydroxyurea for hyperleukocytosis
- At least 3 months since prior chemotherapy for MDS or chronic myeloproliferative disorders antecedent to AML
- No other concurrent chemotherapy
- No concurrent corticosteroids as anti-emetics
- No concurrent steroids except for adrenal failure or septic shock
- No concurrent hormonal therapy except hormones for non-disease-related conditions (e.g., insulin for diabetes, tamoxifen or equivalent for breast cancer prevention or adjuvant treatment, or estrogens or progestins for gynecologic indications)
- No prior radiotherapy for primary AML except cranial radiotherapy for CNS leukostasis
- No concurrent palliative radiotherapy
- No concurrent whole brain radiotherapy
- No other concurrent investigational or commercial agents or therapies
- No concurrent cyclooxygenase-2 inhibitors
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
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실험적: Arm I
INDUCTION THERAPY: Patients receive oblimersen (G3139) IV continuously on days 1-10 and cytarabine IV continuously on days 4-10. Patients also receive daunorubicin IV daily on days 4-6. Patients with bone marrow cellularity of at least 20% and at least 5% leukemic blasts at day 17 or evidence of refractory disease receive a second induction comprising G3139 IV continuously on days 1-8, cytarabine IV continuously on days 4-8, and daunorubicin IV on days 4-5. CONSOLIDATION THERAPY: Beginning no sooner than 14 days after hematologic recovery from induction therapy, patients receive G3139 IV continuously on days 1-8 and cytarabine IV over 4 hours on days 4-8. Patients receive a second course of consolidation therapy no sooner than 14 days after hematologic recovery from the first course. |
상관 연구
주어진 IV
다른 이름들:
상관 연구
다른 이름들:
주어진 IV
다른 이름들:
주어진 IV
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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MTD of cytarabine and daunorubicin in combination with G3139, defined as the dose level just below the dose level at which DLT is observed in 2 patients, graded according to NCI CTC version 2.0
기간: Up to day 10
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Up to day 10
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Incidence of adverse events, graded according to NCI CTC version 2.0
기간: Up to 2 years
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We will define the qualitative and quantitative toxicities in regard to organ specificity, time course, predictability, and reversibility.
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Up to 2 years
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2차 결과 측정
결과 측정 |
기간 |
|---|---|
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전반적인 생존
기간: 최대 2년
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최대 2년
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Pharmacokinetics of G3139
기간: During induction therapy on day 1 at hour 0 and 24hours after G3139 administration; day 4 at hour 73 before cytarabine administration; day 11 at hour 0 and .5, 1, 2, 4, 6, and 8 hours
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During induction therapy on day 1 at hour 0 and 24hours after G3139 administration; day 4 at hour 73 before cytarabine administration; day 11 at hour 0 and .5, 1, 2, 4, 6, and 8 hours
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Level of bcl-2 in circulating and/or marrow leukemic blasts before and after initiation of treatment with G3139
기간: Up to 18 weeks
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Up to 18 weeks
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Spontaneous rate of apoptosis in leukemic blasts before and after initiation of treatment with G3139
기간: Up to 18 weeks
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Up to 18 weeks
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Incidence of therapeutic response (complete remission [CR])
기간: Up to 2 years
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Up to 2 years
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무질병 생존
기간: 최대 2년
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최대 2년
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공동 작업자 및 조사자
수사관
- 수석 연구원: Guido Marcucci, Ohio State University
연구 기록 날짜
연구 주요 날짜
연구 시작
기본 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
연구 기록 업데이트
마지막 업데이트 게시됨 (추정)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- NCI-2012-01409
- U01CA076576 (미국 NIH 보조금/계약)
- OSU-0164
- NCI-4630
- CDR0000069353
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