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Decitabine and Gemtuzumab Ozogamicin in Acute Myelogenous Leukemia (AML) and High-Risk Myelodysplastic Syndrome (H-R MDS)

2013년 9월 3일 업데이트: M.D. Anderson Cancer Center

Phase II Study of Decitabine and Gemtuzumab Ozogamicin in Acute Myelogenous Leukemia and High-Risk Myelodysplastic Syndrome

The goal of this clinical research study is to learn if 5-aza-2 deoxycytidine (decitabine) given in combination with Mylotarg (gemtuzumab ozogamicin) can help to control Acute myeloid leukemia (AML), high-risk myelodysplastic syndromes (MDS) or Myelofibrosis (MF). The safety of this drug combination will also be studied.

연구 개요

상세 설명

The Study Drugs:

Gemtuzumab ozogamicin is designed to attach to Sialic acid-binding Ig-like lectin 3 (CD33), a certain protein that is often found in leukemia cells, causing them to die.

Decitabine is designed to damage the Deoxyribonucleic acid (DNA) (the genetic material) of cells, which may cause cancer cells to die.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive decitabine through a needle in your vein over 1 and 1/2 hours on Days 1-5 of each cycle. You will also receive gemtuzumab ozogamicin by vein over about 1 hour after you receive decitabine on Day 5 of each 4-8 week cycle.

During Cycle 1 only, if a bone marrow test done 2 weeks after you receive your first study drug treatment shows abnormal leukemia cells, you will receive another treatment with decitabine by vein over 1 and 1/2 hours for 5 days.

Gemtuzumab may cause allergic reactions, nausea, and vomiting. To help decrease the risk of such side effects, you will receive Benadryl (diphenhydramine), acetaminophen, meperidine, and hydrocortisone. You may receive these drugs by vein, or by mouth on each of the days you get gemtuzumab ozogamicin.

Study Visits:

At every study visit, you will be asked if you have experienced side effects and to list any drugs you may be taking.

During Cycle 1, blood (about 2 teaspoons) will be drawn at least 1 time each week for routine tests. If the doctor thinks it is necessary, you may be asked to have additional blood drawn.

On Day 1 of every cycle, your performance status will be recorded and your vital signs will be measured.

On Days 1-5 of Cycle 1, your vital signs will be measured.

Between Days 12 and 16 of Cycle 1, you will have a bone marrow aspirate if you have a diagnosis of AML or high-risk MDS to check the status of the disease. This test may be delayed if your doctor does not think you are in remission.

During Cycles 2-3, blood (about 2 teaspoons) will be drawn for routine tests at least 2 times each month.

On Day 1 of Cycles 2 and beyond, you will have a physical exam, including measurement of your vital signs.

During Cycles 4 and beyond, blood (about 2 teaspoons) will be drawn for routine tests at least 1 time each month.

If the doctor thinks it is necessary, you will have a bone marrow aspirate every 1-3 months to check the status of the disease.

You should tell the study doctor about all drugs and supplements you are taking while you are on this study.

Length of Study:

You may receive the combination of decitabine and gemtuzumab ozogamicin for up to 6 cycles. After this, if your doctor thinks it is in your best interest, you may continue to receive decitabine alone for up to 24 cycles. During this part of study, your performance status will be recorded, you will have a physical exam, and your vital signs will be measured on Day 1 of each cycle. Blood (about 2 teaspoons) will be drawn for tests once a month. You will be taken off study early if the disease gets worse, you experience intolerable side effects, or your doctor thinks that it is no longer in your best interest to receive the study drug(s).

Long-Term Follow-up:

Once you are off study, you will have follow-up visits every month for up to 2 years. At these visits, blood (about 2 teaspoons) will be drawn for routine tests.

This is an investigational study. Gemtuzumab ozogamicin is FDA approved and commercially available for the treatment of AML that has come back after treatment in patients over the age of 65 years. Decitabine is FDA approved and commercially available for the treatment of MDS. The use of gemtuzumab ozogamicin and decitabine in combination is investigational.

Up to 100 participants will take part in this study. All will be enrolled at The University of Texas (UT) MD Anderson Cancer Center.

연구 유형

중재적

등록 (실제)

43

단계

  • 2 단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 장소

    • Texas
      • Houston, Texas, 미국, 77030
        • UT MD Anderson Cancer Center

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

16년 이상 (어린이, 성인, 고령자)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

Inclusion Criteria:

  1. Understand and voluntarily sign an informed consent form.
  2. Age >/= to 16 years at the time of signing the informed consent form.
  3. Diagnosis of AML [other than acute promyelocytic leukemia (APL)] with refractory/relapsed disease. Patients with newly diagnosed AML will be eligible if not a candidate for intensive chemotherapy. Patients with high-risk (intermediate-2 or high by International Prognostic Scoring System (IPSS) or >/= 10% blasts) MDS will also be eligible. All non-hematological toxicity of previous cancer therapy should have resolved to </= grade 1 (except alopecia or other toxicities not involving major organs).
  4. Eastern Cooperative Oncology Group (ECOG) performance status of </=3 at study entry.
  5. Laboratory test results within these ranges (unless due to leukemia): Serum creatinine </= 2 mg/dL Total bilirubin </= 2 mg/dL aspartate aminotransferase (AST) (SGOT) and/or alanine aminotransferase (ALT) (SGPT) </= 2.5 * upper limit of normal (ULN) or </= 5 * ULN if related to disease
  6. Women of childbearing potential (WCBP) must have a negative urine pregnancy test within 7 days and must either commit to continued abstinence from heterosexual intercourse or adopting at least one highly effective method of contraception. These methods include intra-uterine device, tubal ligation, partner's vasectomy, hormonal birth control pills. Men must agree not to father a child and agree to use a condom if his partner is of child bearing potential.
  7. Active participants of the similar Protocol 2007-0882 (preceding study of decitabine and Mylotarg) are eligible to roll-over to this protocol without meeting the inclusion or exclusion criteria for this study.
  8. For patients with MF only: Diagnosis of MF requiring therapy, including those previously treated by MF-directed therapy and relapsed or refractory; or if newly diagnosed then with intermediate or high risk according to Lille scoring system (adverse prognostic factors are: hemoglobin (Hb) < 10 g/dl, White blood cells (WBC) < 4 or > 30 * 10^9/L; risk group: 0 = low, 1 = intermediate, 2 = high), or with symptomatic splenomegaly (>/=10cm below left mid-costal margin).
  9. For patients with MF only: Performance status 0-2 (Zubrod).
  10. For patients with MF only: Signed informed consent.
  11. For patients with MF only: Patients must have been off MF-directed therapy for 2 weeks prior to entering this study and have recovered from the toxic effects (grade 0-1) of that therapy. Patients are allowed to enter the study if on stable dose, for at least 1 months, of anagrelide (to control high platelets) or hydroxyurea (to control high WBC or enlarging spleen), or on stable dose, for at least 2 months, of erythropoietin (for significant anemia).
  12. For patients with MF only: Serum bilirubin levels </= 2 times the upper limit of the normal range for the laboratory (ULN). Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis, as judged by treating physician.
  13. For patients with MF only: Serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) levels </= 2* ULN, unless related to the MF, as judged by treating physician.
  14. For patients with MF only: Serum creatinine levels </= 2* ULN.
  15. For patients with MF only: Women of childbearing potential must have a negative serum pregnancy test prior to treatment and should be advised to avoid becoming pregnant. Men must be advised to not father a child while receiving treatment. Both women of childbearing potential and men must practice effective methods of contraception (those generally accepted as standard of care measures).
  16. For patients with MF only: Age > 18 years.

Exclusion Criteria:

  1. Pregnant or breastfeeding females.
  2. Any condition, including the presence of laboratory abnormalities, which places the patient at unacceptable risk.
  3. Use of any other experimental drug or therapy for leukemia within 14 days unless there is clear evidence of rapid disease progression. Use of hydrea to control proliferative disease will be allowed prior to starting therapy on study and for up to 7 days each during cycle 1-3 (Maximum daily dose of 7 gm).
  4. For patients with MF only: Nursing and pregnant females. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  5. For patients with MF only: Uncontrolled intercurrent illness including, but not limited to, uncontrolled active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.

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
실험적: Decitabine + Gemtuzumab Ozogamicin
Decitabine 20 mg/m^2 by vein (IV) over 1-1/2 hours daily for 5 days. Gemtuzumab ozogamicin 3 mg/m^2 by vein on day 5.
Decitabine 20 mg/m^2 IV over 1-1/2 hours daily for 5 days.
다른 이름들:
  • 다코젠®
Gemtuzumab ozogamicin 3 mg/m^2 IV on day 5.
다른 이름들:
  • 마일로타그®

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Number of Participants With a Complete Response
기간: Day 14 of first cycle
Complete Response (CR) was defined as normalization of peripheral blood and bone marrow with </= 5% blasts, a peripheral absolute neutrophil count (ANC) >/= 1 * 10^9 /l, and a platelet count of >/= 100 & 10^9 /l. Approximately Day 14 of the first cycle of 4 - 8 week cycle, a bone marrow aspirate was performed to check the status of the disease using International Working Group (IWG) criteria for acute myelogenous leukemia (AML) and myelofibrosis (MF).
Day 14 of first cycle

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

협력자

수사관

  • 수석 연구원: Gautam Borthakur, M.D., M.D. Anderson Cancer Center

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

2009년 4월 1일

기본 완료 (실제)

2012년 8월 1일

연구 완료 (실제)

2012년 8월 1일

연구 등록 날짜

최초 제출

2009년 4월 15일

QC 기준을 충족하는 최초 제출

2009년 4월 15일

처음 게시됨 (추정)

2009년 4월 16일

연구 기록 업데이트

마지막 업데이트 게시됨 (추정)

2013년 9월 13일

QC 기준을 충족하는 마지막 업데이트 제출

2013년 9월 3일

마지막으로 확인됨

2013년 9월 1일

추가 정보

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. .

골수 형성 이상 증후군에 대한 임상 시험

Decitabine에 대한 임상 시험

3
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