Alvocidib in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
A Phase I Dose-Escalation Study of Flavopiridol (NSC 649890) Administered as a 30 Minute Loading Dose Followed by a 4-Hour Infusion in Patients With B-Cell Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) Following Cytoreduction With Chemotherapy
연구 개요
상태
정황
개입 / 치료
상세 설명
PRIMARY OBJECTIVES:
I. Determine the toxicity profile, dose-limiting toxicity, and maximum tolerated dose of flavopiridol (alvocidib) as consolidation chemotherapy after cytoreduction chemotherapy in patients with B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma.
SECONDARY OBJECTIVES:
I. Determine the pharmacokinetics and cellular pharmacodynamics of flavopiridol in these patients.
II. Determine the complete response (CR) and overall response rate (CR and partial response) of patients treated with flavopiridol.
OUTLINE: This is a dose-escalation study. Patients receive alvocidib intravenously (IV) over 30 minutes (loading dose), followed by alvocidib IV over 4 hours on days 1, 8, and 15.
Treatment repeats every 5 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of flavopiridol 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. A total of 12 patients are treated at the MTD (i.e., recommended phase II dose). Patients undergo blood collection at baseline and periodically during study for pharmacokinetic and cytokine studies (levels of tumor necrosis factor-alpha, interleukin [IL]-6, -11, and -16) by enzyme-linked immunosorbent assay (ELISA). Interphase cytogenetics, p53 mutational status, p53/ATM function, V_H mutational status, zeta-chain-associated protein kinase 70 (ZAP-70) overexpression, and single nucleotide polymorphisms are also examined.
After completion of study treatment, patients are followed at 2 months and then every 3 months for 5 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:
Diagnosis of 1 of the following:
- B-cell chronic lymphocytic leukemia (CLL)
- Small lymphocytic lymphoma (SLL)
Must have received 1-3 prior therapies for CLL
- Completed therapy 2-12 months ago
- Prior therapy must have led to a partial response or greater
- No evidence of progressive disease
- ECOG performance status 0-2
- Absolute neutrophil count ≥ 1,000/mm³
- WBC ≤ 5,000/mm³
- Platelet count ≥ 50,000/mm³
- Cytopenia allowed
- Creatinine < 2.0 mg/dL
- Bilirubin ≤ 1.5 times normal (unless due to Gilbert's disease or hemolysis)
- AST ≤ 2 times normal (unless due to hemolysis)
- No secondary malignancy or other disease that would limit survival to < 2 years
- No history of inflammatory bowel disease unless inactive for > 2 years
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- See Disease Characteristics
- No other concurrent chemotherapy
- No concurrent radiotherapy
- No concurrent dexamethasone or other corticosteroid-based antiemetics
- No concurrent chronic corticosteroid therapy
No other concurrent hormonal therapy except for the following:
- Steroids for new adrenal failure
- Hormones for nondisease-related conditions (e.g., insulin for diabetes)
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: Treatment (chemotherapy)
Patients receive alvocidib IV over 30 minutes (loading dose), followed by alvocidib IV over 4 hours on days 1, 8, and 15.
Treatment repeats every 5 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.
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상관 연구
주어진 IV
다른 이름들:
상관 연구
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Toxicity profile of alvocidib administered as a 30 minute loading dose followed by a 4-hour infusion once weekly for 3 consecutive weeks every 5 weeks as consolidation therapy following cytoreduction chemotherapy
기간: Day 1, every 2 courses, at 2 months and then every 3 months for 5 years after completion of study treatment
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Assessed utilizing the NCI Common Terminology Criteria for Adverse Events version 3.0.
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Day 1, every 2 courses, at 2 months and then every 3 months for 5 years after completion of study treatment
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Dose-limiting toxicity of alvocidib as consolidation chemotherapy after cytoreduction chemotherapy in patients with B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma
기간: Course 1
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The National Cancer Institute Common Toxicity Criteria version 3.0 will be used to characterize toxicity.
If no patients experience dose-limiting toxicity, dose escalation will occur.
If 1 patient has a dose limiting toxicity, 3 additional patients will be enrolled at that dose.
If fewer than 2 of 6 patients experiences dose limiting toxicity, then the next highest dose level will be used for the subsequent cohort of 3 patients.
If at any dose level two or more of the six patients experience a dose limiting toxicity, 3 additional patients will be treated at the previous dose level.
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Course 1
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Pharmacokinetics and cellular pharmacodynamics of alvocidib administered in this schedule
기간: Baseline and day 1
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Cytokine studies will be examined by standard ELISA assays to determine if increase IL-6 correlates with hypotension, hypoxemia, and tachycardia observed following treatment and to identify the source of production of this cytokine.
We will examine interphase cytogenetics, p53 mutational status, p53/ATM functional assay, VH mutational status, and ZAP-70 over-expression.
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Baseline and day 1
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Complete response (CR) and overall response rate (CR and partial response) of alvocidib in patients with previously-treated CLL
기간: Baseline, every 2 courses, at 2 months and then every 3 months for 5 years after completion of study treatment
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Criteria for response will utilize the Revised National Cancer Institute-sponsored Working Group Guidelines.
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Baseline, every 2 courses, at 2 months and then every 3 months for 5 years after completion of study treatment
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공동 작업자 및 조사자
수사관
- 수석 연구원: Leslie Andritsos, Ohio State University
간행물 및 유용한 링크
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-2009-00161
- U01CA076576 (미국 NIH 보조금/계약)
- OSU 05116
- OSU-IRB-2006C0031
- CDR0000501975
- OSU-05116
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .
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