Interleukin-12 and Interleukin-2 in Treating Patients With Refractory or Recurrent Neuroblastoma
A Phase I Investigation of IL-12 (NSC 672423)/Pulse IL-2 (Aldesleukin) in Children With Persistent and/or Refractory Neuroblastoma (13623)
연구 개요
상세 설명
OBJECTIVES:
I. Define the maximum tolerated dose and dose-limiting toxicity of interleukin-12 with or without interleukin-2 in patients with refractory or recurrent neuroblastoma.
II. Determine, preliminarily, the antitumor effect of interleukin-12 with or without interleukin-2 in these patients.
III. Evaluate the immunoregulatory activity of interleukin-12 with or without interleukin-2 in these patients.
IV. Evaluate the antiangiogenic activity of interleukin-12 with or without interleukin-2 in these patients.
OUTLINE: This is a dose-escalation, multicenter study. Patients are assigned to 1 of 2 treatment cohorts.
COHORT A: Patients receive interleukin-12 (IL-12) IV over 5-15 seconds on days 1, 3, 5, 8, 10, and 12.
COHORT B: Patients receive interleukin-2 (IL-2) IV over 15 minutes twice daily on days 1 and 8 and IL-12 IV as in cohort A.
Treatment in both cohorts repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Some patients may receive additional courses at the discretion of the principal investigator.
Cohorts of 3-6 patients in both cohorts receive escalating doses of IL-2 and IL-12 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.
Once the MTD is determined, an additional cohort of 8 patients receives IL-12 and IL-2 at the MTD.
Patients are followed at 3 weeks.
연구 유형
등록 (실제)
단계
- 1단계
연락처 및 위치
연구 장소
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California
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Los Angeles, California, 미국, 90027
- Children's Hospital Los Angeles
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Los Angeles, California, 미국, 90027-6016
- New Approaches to Neuroblastoma Treatment (NANT)
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Palo Alto, California, 미국, 94304
- Lucile Packard Children's Hospital Stanford University
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San Francisco, California, 미국, 94143-0875
- University of California at San Francisco - Comprehensive Cancer Center
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Georgia
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Atlanta, Georgia, 미국, 30322
- AFLAC Cancer Center and Blood Disorders Service
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Illinois
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Chicago, Illinois, 미국, 60614
- Childrens Memorial Hospital
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Indiana
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Indianapolis, Indiana, 미국, 46202
- Riley Hospital for Children
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Massachusetts
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Boston, Massachusetts, 미국, 02115
- Children's Hospital Boston
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Michigan
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Ann Arbor, Michigan, 미국, 48109
- University of Michigan University Hospital
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Ohio
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Cincinnati, Ohio, 미국, 45229
- Cincinnati Children's Hospital Medical Center
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Pennsylvania
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Philadelphia, Pennsylvania, 미국, 19104
- Children's Hospital of Philadelphia
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Texas
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Houston, Texas, 미국, 77030
- Texas Children's Hospital
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Washington
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Seattle, Washington, 미국, 98105
- Seattle Children's Hospital
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Wisconsin
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Madison, Wisconsin, 미국, 53792
- University of Wisconsin Hospital and Clinics
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
Diagnosis of neuroblastoma
- Histologically confirmed disease AND/OR disease defined by tumor cells in the bone marrow and elevated urinary catecholamine metabolites
Persistent and/or refractory disease, with at least 1 of the following:
- Biopsy-proven residual disease at least 12 weeks after myeloablative therapy
- Progressive disease after nonmyeloablative or myeloablative therapy
Recurrent disease, evidenced by any of the following:
- Biopsy-proven recurrent soft tissue disease
- Metaiodobenzylguanidine (MIBG)-positive lesions visible on any other imaging modality or repeat MIBG obtained 2-4 weeks or more apart
- Histologically confirmed bone marrow disease
- Progressive or stable disease after at least 1 prior standard salvage regime
- No clinically significant pleural effusion
- ECOG 0-1
- Life expectancy >= 12 weeks
- Hepatitis A antibody negative
Hepatitis B surface antigen negative
- Positive hepatitis B titer allowed if patient has been immunized and has no history of disease
- Hepatitis C virus negative
- No history of congenital or acquired coagulation disorder
- Cardiac function normal by ECG
- No dyspnea at rest
- No exercise intolerance
- Oxygen saturation at least 94% by pulse oximetry
- DLCO greater than 60% of predicted
- FEV1 greater than 70% of predicted
- Negative pregnancy test
- Skull-based bony lesions without space-occupying intracranial extension are allowed
- No prior or concurrent intracranial metastatic disease to the brain parenchyma
- Not pregnant or nursing
- Fertile patients must use effective barrier contraception during and for at least 2 months after study
- No prior hematologic malignancy (including leukemia or lymphoma)
- No history of malignant hyperthermia
- No prior or concurrent autoimmune disease
- No positive direct Coombs testing
- No history of ongoing or intermittent bowel obstruction
- No active infection or other significant systemic illness
- More than 2 weeks since prior fenretinide
- More than 2 weeks since prior 13-cis-retinoic acid
- More than 2 weeks since prior filgrastim (G-CSF) or sargramostim (GM-CSF)
- More than 2 weeks since prior interferons or interleukins
- More than 2 weeks since prior cytokine-fusion proteins
- More than 2 weeks since prior IV immunoglobulin (IVIG)
- No prior interleukin-12
- No concurrent cytokines
- No concurrent fenretinide
- No concurrent 13-cis-retinoic acid
No other concurrent immunomodulators, including:
- G-CSF and GM-CSF
- Interferons
- Other interleukins
- IVIG
- More than 4 weeks since prior chemotherapy
- No other unstable medical condition or critical illness that would preclude study participation
- More than 12 weeks since prior myeloablative chemotherapy followed by autologous stem cell transplantation:
No prior myeloablative chemotherapy followed by allogeneic bone marrow transplantation
- More than 2 weeks since prior growth hormones
- More than 4 weeks since prior systemic corticosteroids
- More than 2 weeks since prior non-corticosteroid hormonal therapy (including oral birth control pills)
- No concurrent hormonal therapy (including oral birth control pills)
- No concurrent growth hormones
- No concurrent systemic corticosteroids, except for use in life-threatening complications
- More than 4 weeks since prior radiotherapy
- No prior solid organ transplantation
- More than 4 weeks since prior investigational agents
- No other concurrent investigational agents
- No prior enrollment on COG-A3973, unless disease has progressed
- No history of hemolytic anemia
- Absolute neutrophil count at least 1,500/mm^3 [Note: Independent of growth factor or transfusion support]
- Platelet count at least 75,000/mm^3 [Note: Independent of growth factor or transfusion support]
- AST and ALT less than 2.5 times upper limit of normal
- Bilirubin less than 2.0 mg/dL
- Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min OR creatinine normal
- HIV negative
- Ejection fraction at least 50% by echocardiogram or MUGA OR Fractional shortening at least 30% by echocardiogram
- No congestive heart failure
- No uncontrolled cardiac arrhythmia
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 |
|---|---|
|
실험적: Treatment (IL-12, aldesleukin)
Cohort A: Patients receive interleukin-12 (IL-12) IV over 5-15 seconds on days 1, 3, 5, 8, 10, and 12. Cohort B: Patients receive interleukin-2 (IL-2) IV over 15 minutes twice daily on days 1 and 8 and IL-12 IV as in cohort A. Treatment in both cohorts repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Some patients may receive additional courses at the discretion of the principal investigator. Cohorts of 3-6 patients in both cohorts receive escalating doses of IL-2 and IL-12 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. Once the MTD is determined, an additional cohort of 8 patients receives IL-12 and IL-2 at the MTD. |
주어진 IV
다른 이름들:
주어진 IV
다른 이름들:
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
기간 |
|---|---|
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Maximum tolerated dose (MTD) assessed by Common Toxicity Criteria (CTC)
기간: 28 days
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28 days
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2차 결과 측정
결과 측정 |
기간 |
|---|---|
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Overall response assessed by Response Evaluation Criteria for Solid Tumors (RECIST)
기간: Up to 3 weeks
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Up to 3 weeks
|
공동 작업자 및 조사자
수사관
- 수석 연구원: Jon Wigginton, New Approaches to Neuroblastoma Treatment (NANT)
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-2009-00024
- P01CA081403 (미국 NIH 보조금/계약)
- NANT 2001-01
- CDR0000270447 (레지스트리 식별자: PDQ (Physician Data Query))
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