- ICH GCP
- 미국 임상 시험 레지스트리
- 임상시험 NCT00077558
3-AP Followed By Fludarabine In Treating Patients With Relapsed or Refractory Acute or Chronic Leukemia or High-Risk Myelodysplastic Syndrome
A Phase I Trial Of Sequential Administration Of Triapine (3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone) Followed By Fludarabine In Adults With Relapsed And Refractory Leukemias And Myelodysplasias
RATIONALE: Drugs used in chemotherapy, such as fludarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. 3-AP may help fludarabine kill more cancer cells by making them more sensitive to the drug.
PURPOSE: This phase I trial is studying the side effects and best dose of fludarabine when given together with 3-AP in treating patients with relapsed or refractory acute leukemia, chronic leukemia, or high-risk myelodysplastic syndrome.
연구 개요
상세 설명
OBJECTIVES:
- Determine the feasibility and tolerability of 3-AP (Triapine^® ) followed by fludarabine in patients with relapsed or refractory acute or chronic leukemia or high-risk myelodysplastic syndromes.
- Determine the toxic effects of this regimen in these patients.
- Determine the maximum tolerated dose of this regimen in these patients.
OUTLINE: This is a multicenter, dose-escalation study of fludarabine. Patients are stratified according to disease (acute leukemias and myelodysplastic syndromes [MDS] vs chronic lymphocytic leukemia and prolymphocytic leukemia). Patients are assigned to 1 of 2 treatment groups.
- Group 1 (chronic lymphocytic leukemia or prolymphocytic leukemia): Patients receive 3-AP (Triapine^®) IV over 4 hours and fludarabine IV over 30 minutes on days 1-5.
Cohorts of 3-6 patients receive escalating doses of fludarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 10 additional patients are treated at that dose level.
- Group 2 (acute leukemias or MDS): Patients receive 3-AP IV continuously over 24 hours on day 1. Beginning within 4 hours after completion of 3-AP, patients receive fludarabine IV over 30 minutes on days 2-6.
In both groups, treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
PROJECTED ACCRUAL: A total of 3-34 patients will be accrued for this study.
연구 유형
단계
- 1단계
연락처 및 위치
연구 장소
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Georgia
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Atlanta, Georgia, 미국, 30342-4777
- Blood and Marrow Transplant Group of Georgia
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Maryland
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Baltimore, Maryland, 미국, 21231
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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Baltimore, Maryland, 미국, 21201
- Greenebaum Cancer Center at University of Maryland Medical Center
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Texas
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Houston, Texas, 미국, 77030-4095
- M.D. Anderson Cancer Center at University of Texas
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
DISEASE CHARACTERISTICS:
Histologically confirmed diagnosis of 1 of the following:
High-risk myelodysplastic syndromes (MDS), including refractory anemia with excess blasts and chronic myelomonocytic leukemia
International Prognostic Scoring System (IPSS) score at least 1.5 based on the following:
- More than 10% marrow blasts
- Cytopenias in at least 2 lineages
- Adverse cytogenetics
Acute myeloid leukemia (AML)
- All subtypes, including MDS/AML and treatment-related (secondary) AML
- Acute lymphoblastic leukemia
Acute progranulocytic leukemia
- Ineligible for arsenic therapy
Chronic myelogenous leukemia
- Accelerated phase or blastic crisis
- Chronic lymphocytic leukemia
- Prolymphocytic leukemia
- Received or ineligible for established curative regimens, including stem cell transplantation
- Acute and chronic leukemias must be relapsed and/or refractory with progressive disease since last therapy
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-2
Life expectancy
- Not specified
Hematopoietic
- No history of hemolytic anemia grade 2 or greater
No known glucose-6-phosphate dehydrogenase (G6PD) deficiency
- G6PD screening required for high-risk groups (i.e., patients of African, Asian, or Mediterranean origin/ancestry)
Hepatic
- SGOT and SGPT no greater than 2.5 times normal
- Bilirubin no greater than 2 mg/dL
- No chronic hepatitis
Renal
- Creatinine normal OR
- Creatinine clearance at least 60 mL/min
Cardiovascular
- No active heart disease
- No myocardial infarction within the past 3 months
- No severe coronary artery disease
- No arrhythmias (other than atrial flutter or fibrillation) requiring medication
- No uncontrolled congestive heart failure
Pulmonary
- No dyspnea at rest or with minimal exertion
- No severe pulmonary disease requiring supplemental oxygen
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No neuropathy grade 2 or greater
No active uncontrolled infection
- Infections under active treatment and controlled by antibiotics are allowed
- No other life-threatening illness
- No psychiatric illness that would preclude study compliance
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
- At least 1 week since prior hematopoietic growth factor (e.g., epoetin alfa, filgrastim [G-CSF], sargramostim [GM-CSF], interleukin-3, and interleukin-11)
- No concurrent immunotherapy
Chemotherapy
- Recovered from prior chemotherapy (no greater than grade 1 chronic toxic effects)
- At least 72 hours since prior hydroxyurea
- At least 3 weeks since prior myelosuppressive cytotoxic agents (6 weeks for mitomycin or nitrosoureas)
- No more than 12 prior courses of fludarabine
- No more than 3 prior cytotoxic chemotherapy regimens
- No other concurrent chemotherapy
Endocrine therapy
- Not specified
Radiotherapy
- At least 2 weeks since prior radiotherapy
- No concurrent radiotherapy
Surgery
- Not specified
Other
- At least 1 week since prior non-myelosuppressive treatment
- No more than 4 prior induction regimens
- No other concurrent therapy
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
공동 작업자 및 조사자
간행물 및 유용한 링크
연구 기록 날짜
연구 주요 날짜
연구 시작
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
키워드
- 과도한 돌풍을 동반한 난치성 빈혈
- 만성 골수단구성 백혈병
- 이전에 치료받은 골수이형성 증후군
- 속발성 골수이형성 증후군
- 11q23(MLL) 이상이 있는 성인 급성 골수성 백혈병
- inv(16)(p13;q22)가 있는 성인 급성 골수성 백혈병
- t(15;17)(q22;q12)가 있는 성인 급성 골수성 백혈병
- t(16;16)(p13;q22)가 있는 성인 급성 골수성 백혈병
- t(8;21)(q22;q22)가 있는 성인 급성 골수성 백혈병
- 속발성 급성 골수성 백혈병
- 재발성 성인 급성 골수성 백혈병
- 비정형 만성 골수성 백혈병
- 골수이형성/골수증식성 질환, 분류 불가
- 성인 급성 적혈구성 백혈병(M6)
- 성인 급성 거핵모구성 백혈병(M7)
- 성인 급성 최소 분화 골수성 백혈병(M0)
- 성인 급성 단구성 백혈병(M5a)
- 성인 급성 단핵구 백혈병(M5b)
- 성숙한 성인 급성 골수성 백혈병(M2)
- 성숙하지 않은 성인 급성 골수성 백혈병(M1)
- 성인 급성 골수단구성 백혈병(M4)
- 성인 급성 호염기성 백혈병
- 성인급성호산구성백혈병
- 모세포기 만성 골수성 백혈병
- 재발성 만성 골수성 백혈병
- 난치성 만성 림프 구성 백혈병
- 재발성 성인 급성 림프구성 백혈병
- 전림프구성 백혈병
- 가속기 만성 골수성 백혈병
- 성인 급성 전골수성 백혈병(M3)
추가 관련 MeSH 약관
기타 연구 ID 번호
- CDR0000352322, J0357
- P30CA006973 (미국 NIH 보조금/계약)
- U01CA070095 (미국 NIH 보조금/계약)
- JHOC-J0357
- NCI-6255
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