- ICH GCP
- 미국 임상 시험 레지스트리
- 임상시험 NCT00840931
Immunotherapy Using Lenalidomide + Bystander Vaccine in High Risk Myelodysplastic Syndrome (MDS)
2019년 12월 10일 업데이트: H. Lee Moffitt Cancer Center and Research Institute
A Phase I Pilot Study of Immunotherapy Using Lenalidomide Plus "Bystander" Vaccine in Patients With High-Risk Myelodysplastic Syndrome (MDS)
The purpose of this study is to find out the maximum tolerated dose (MTD) of the combined therapy of lenalidomide (Revlimid®) and Granulocyte/macrophage colony stimulating factor and CD40 Ligand expressed in the K562 cell line (GM.CD40L) bystander vaccine.
This research is also being done to see how well the combination of these drugs works to fight myelodysplastic syndrome (MDS).
연구 개요
상세 설명
Fixed dose of lenalidomide at 10 mg/day, Days 1- 21 of 28 days of treatment cycle, and 4 dose escalations of GM.CD40L vaccine: 10 X 10^6 GM.CDL cells per vaccination; 30 X 10^6 GM.CDL cells per vaccination; 60 X 10^6 GM.CDL cells per vaccination; 120 X 10^6 GM.CDL cells per vaccination; Vaccination at 2-week intervals, on days 8 and 22, for a total of four 28-day cycles.
연구 유형
중재적
등록 (실제)
22
단계
- 1단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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Florida
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Tampa, Florida, 미국, 33612
- H. Lee Moffitt Cancer Center & Research Institute
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참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
18년 이상 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
Inclusion Criteria:
- Must understand and voluntarily sign an informed consent form
- Age ≥18 years at the time of signing the informed consent form
- Able to comply with the study visit schedule and assessments required by the protocol
- Documented diagnosis of MDS with subtypes of Refractory Anemia with Excess Blast 1 (RAEB-1) (myeloblast ≥5-9%) or Refractory Anemia with Excess Blast 2 (RAEB-2) (myeloblast ≥10-19%) or intermediate 2, Acute myelogenous leukemia with bone marrow myeloblast >30% and high risk defined by International Prognostic Scoring System (IPSS) scores or refractory anemia with excess blast in transformation (RAEB-t) (myeloblast ≥ 20-30%) as per French-American-British Classification System (FAB) criteria. Any single or combination of cytogenetic abnormalities is allowed.
- Study treatment can be offered as first line treatment as long as the available food and Drug Administration (FDA) approved treatment options are explained by the treating physician and the participant declines such options.
- Study treatment can be offered to patients who have failed, cannot tolerate or do not wish to continue other therapeutic agents for MDS.
- Prior chemotherapy is allowed but should be off chemotherapy of any kind for at last 4 weeks prior to initiation of study therapy.
- Must be able to provide adequate bone marrow (BM) aspirate and biopsy specimens for histopathological evaluation, cytogenetic analysis and tissue banking during the screening procedure.
- Platelet count must be > 20,000/ µl without platelet transfusion.
- Absolute neutrophil count (ANC) must be >500/ µl without myeloid growth factor support.
- Should not be receiving erythropoietin and/or myeloid growth factor for at least 14 days prior to initiation of study therapy.
- Should not have current diagnosis or prior history of any autoimmune or immune deficiency disorders including human immunodeficiency virus positive/acquired immunodeficiency syndrome (HIV+/AIDS).
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
- Both male and female and members of all races and ethnic groups are eligible for this study.
Exclusion Criteria:
- Prior therapy with lenalidomide.
- Proliferative chronic myelomonocytic leukemia (CMML with WBC≥12,000/µL in peripheral blood), confirmed by bone marrow biopsy.
- Acute myelogenous leukemia with bone marrow myeloblast ≥30%
- MDS secondary to treatment with radiotherapy, chemotherapy, and/or immunotherapy for malignant or autoimmune diseases are excluded.
Any of the following laboratory abnormalities:
- Serum creatinine > 1.5 x upper limit of normal (ULN)
- Serum aspartic transaminase (AST) or alanine transaminase (ALT) >2.0 x ULN
- Serum total bilirubin > 2.0 mg/dL (34 µmol/L)
- Prior ≥ grade-2 national Cancer Institute Common Toxicity Criteria (NCI CTC) allergic reaction to thalidomide.
- Prior desquamating (blistering) rash while taking thalidomide.
- Prior allergic reaction to vaccination of any sort.
- Participants with ≥ grade-2 neuropathy.
- Clinically significant anemia due to factors such as iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis or gastrointestinal bleeding.
- Use of cytotoxic chemotherapeutic agents, growth factors, or experimental agents (agents that are not commercially available) for the treatment of MDS within 28 days of the start of drug treatment.
- Prior history of malignancy other than MDS (except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix) unless the participant has been free of disease for ≥3 years.
- Any serious medical condition or psychiatric illness that will prevent the participant from signing the informed consent form or will place the participant at unacceptable risk if he/she participates in the study.
- Pregnant or nursing females.
- Use of corticosteroids greater than the equivalent of prednisone 10mg daily within 4 weeks of the first vaccination, and on-going need for corticosteroids greater than the equivalent of prednisone 10 mg daily
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
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: Immunotherapy
Participants will take two 5 mg capsules of lenalidomide per day for 21 days followed by 7 days of rest.
This 28 day period is considered 1 cycle.
Participants will receive 4 treatment cycles with 28 days in each cycle.
Those participants showing a clinical response after 4 cycles of treatment may continue to receive lenalidomide as a single agent for additional cycles at the treating Physicians discretion.
During each 28 day cycle participants will also receive GM.CD40L bystander vaccination injections in 2-week intervals on days 8 and 22 for a total of 8 immunizations during the 4 cycle treatment period.
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Patients will take 10 mg capsules of lenalidomide per day for 21 days followed by 7 days of rest.
This 28 day period is considered 1 cycle.
Patients will receive 4 treatment cycles with 28 days in each cycle.
다른 이름들:
In addition to lenalidomide, during each 28 day cycle patients will also receive GM.CD40L bystander vaccination injections in 2-week intervals on days 8 and 22 for a total of 8 immunizations during the 4 cycle treatment period.
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Maximum Tolerated Dose (MTD)
기간: 24 months
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Determination of MTD of GM.CD40L bystander vaccine with lenalidomide in high-risk MDS patients.
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24 months
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Number of Participants with Toxicities
기간: 24 months
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Determination of toxicities associated with combination of GM.CD40L bystander vaccine with lenalidomide in high-risk MDS patients.
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24 months
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Number of Participants with Augmentation of Specific T Cell Immunological Functions
기간: 24 months
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Augmentation of specific T cell immunological functions; T cell proliferation and Interferon-γ production, delayed type hypersensitivity (DTH) sensitivity by lenalidomide.
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24 months
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Number of Participants with Reduction of Bone Marrow Myeloblast
기간: 24 months
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Reduction of bone marrow myeloblast from baseline to post treatment with lenalidomide and GM.CD40L bystander vaccine.
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24 months
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Number of Participants with Improvement of Hemoglobin and/or red blood cell (RBC) Transfusion Independence
기간: 24 months
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Improvement of hemoglobin and/or RBC transfusion independence after combined immunotherapy treatment.
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24 months
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Number of Participants with Resolution of Karyotypic Changes
기간: 24 months
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Resolution of karyotypic changes after combined treatment.
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24 months
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Number of Participants with Augmentation of Other T Cell Parameters
기간: 24 months
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Augmentation of other T cell parameters after the combined treatment.
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24 months
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Duration of Response
기간: 24 months
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Determination of response duration evaluated by Wilms Tumor 1 (WT1) expression and clinical outcomes.
Clinical response will be assessed using International Working Group (IWG) criteria.
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24 months
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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
협력자
수사관
- 수석 연구원: Javier Pinilla, M.D., Ph.D., H. Lee Moffitt Cancer & Research Institute
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (실제)
2009년 2월 2일
기본 완료 (실제)
2014년 2월 17일
연구 완료 (실제)
2019년 12월 1일
연구 등록 날짜
최초 제출
2009년 2월 4일
QC 기준을 충족하는 최초 제출
2009년 2월 10일
처음 게시됨 (추정)
2009년 2월 11일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2019년 12월 11일
QC 기준을 충족하는 마지막 업데이트 제출
2019년 12월 10일
마지막으로 확인됨
2019년 12월 1일
추가 정보
이 연구와 관련된 용어
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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