High Dose Busulfan and Bortezomib in Treating Patients With High Risk Multiple Myeloma Undergoing Stem Cell Transplant
A Pilot Study Using High Dose Busulfan and Bortezomib as Part of Allogeneic Transplant Conditioning Regimen for High Risk Multiple Myeloma Patients.
연구 개요
상태
상세 설명
PRIMARY OBJECTIVES:
I. To determine time to engraftment absolute neutrophil count (> 0.5 x 10^9/L for 3 consecutive days), and platelet (> 20X 109^/L for 3 consecutive days).
2. Incidence and severity of acute graft-versus-host disease (GVHD) using fludarabine (fludarabine phosphate) / busulfan / bortezomib preparative regimen and triple immune suppression with tacrolimus, sirolimus and Thymoglobulin (anti-thymocyte globulin).
3. To determine the safety related to this combination in the first six months post transplant, specifically, treatment related mortality and grade III and IV non hematologic toxicities, based on Common Terminology Criteria for Adverse Events (CTCAE) version 4 (v4).
SECONDARY OBJECTIVES:
I. Incidence of myeloma progression in this high risk group of patients.
II. Incidence of transplant related mortality and morbidity.
III. Incidence of thrombotic thrombocytopenic purpura (TTP) and sinusoidal obstructive syndrome (SOS).
IV. Incidence and severity of chronic GVHD.
V. Incidence of opportunistic infections including cytomegalovirus (CMV), herpes simplex virus (HSV), and Epstein-Barr virus (EBV) reactivation.
I. Overall and progression free survival (PFS) at Day 100, 6 months, 1 & 2 years post transplant.
VII. To determine recovery of T-cell, B cell, and natural killer (NK) cell phenotypes post transplant.
OUTLINE:
CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -7 to -3, busulfan IV on days -6 to -3, and bortezomib IV on day -2.
GVHD PROPHYLAXIS: Patients receive anti-thymocyte globulin IV on days -3 to -1, sirolimus orally (PO) on day -3, and tacrolimus IV on day -3. Patients undergo allogeneic hematopoietic stem cell transplantation (HSCT) on day 0.
After completion of study treatment, patients are followed up for up to 2 years.
연구 유형
등록 (실제)
단계
- 2 단계
연락처 및 위치
연구 장소
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Michigan
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Detroit, Michigan, 미국, 48201
- Barbara Ann Karmanos Cancer Institute
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- Ability to provide informed consent
- Karnofsky Performance Status (KPS) >= 70
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Availability of a suitable allogeneic hematopoietic stem cell donor; minimum of human leukocyte antigen (HLA) 7/8 matched related or unrelated donor
- High risk multiple myeloma with poor prognostic features based on having one or more of the following criteria:
- Progressive disease after autologous transplant. No less than 3 months post auto transplant
- Progressive or stable disease after induction chemotherapy using the most potent myeloma agents Lenalidomide and/or Bortezomib
- Patients with high risk cytogenetic abnormalities documented on conventional cytogenetics or fluorescence in situ hybridization (FISH) (hypodiploidy, t(4:14), t(14:16) chromosome translocation, p53 and or complex cytogenetics) additionally, chromosome 13 deletion by standard cytogenetics
- Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test for women, as well as implementation of birth control for men and women
Exclusion Criteria:
- Patients with prior allogeneic transplant, or more than one prior autologous transplant for any medical reason
- Prior treatment with busulfan or gemtuzumab (Mylotarg ®) for any reason
- Patient with history of allergy to boron, mannitol, or bortezomib
- Creatinine clearance (CrCl) =< 50 ml/min
- Ejection Fraction < 50%
- Diffusion capacity of carbon monoxide (DLCO) < 50% predicted
- Forced expiratory volume in 1 second (FEV1) < 50% predicted
- Forced vital capacity (FVC) < 50% predicted
- Patients with uncontrolled arrhythmia or uncontrolled heart disease at the screening time; patients with coronary heart disease (recent myocardial infarctions, angina, cardiac stent, or bypass surgery in the last 6 months) need to be cleared with a stress echo or nuclear myocardial perfusion stress test, and cardiology consult; all other cardiac history will be at the discretion of the principal investigator
- Liver enzymes > 3 times upper limit normal
- Bilirubin > 2 mg/dl (except Gilbert's disease)
- International normalized ratio (INR) > 2
- Any previous history of liver failure, hepatitis, or cirrhosis
- Systemic Amyloidosis Known history of hepatitis B, C, human immunodeficiency virus (HIV) or any current uncontrolled infection
- Grade > I neuropathy
- Women who are pregnant or lactating
- Current or history of alcohol or drug abuse
- Use of other investigational agents within 30 days of enrollment to this study
- Any patient with ascites
- Any patient on home oxygen
- Any clinical findings on history or physical exam which would in the opinion of the treating physician or principal investigator preclude the patient from participating in the study
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, enzyme inhibitor)
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -7 to -3, busulfan IV on days -6 to -3, and bortezomib IV on day -2. GVHD PROPHYLAXIS: Patients receive thymoglobulin IV on days -3 to -1, sirolimus PO on day -3, and tacrolimus IV on day -3. Patients undergo allogeneic HSCT on day 0. |
상관 연구
주어진 IV
다른 이름들:
상관 연구
다른 이름들:
주어진 IV
다른 이름들:
주어진 PO
다른 이름들:
주어진 IV
다른 이름들:
주어진 IV
다른 이름들:
동종이계 조혈모세포 이식
주어진 IV
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Incidence and Severity of Acute GVHD Using Fludarabine Phosphate / Busulfan / Bortezomib Preparative Regimen and Triple Immune Suppression With Tacrolimus, Sirolimus and Anti-thymocyte Globulin
기간: First 6 months post-transplant
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Graded using the Glucksberg scale.
Proportions and confidence intervals will be estimated.
Estimated using binary proportion estimates as well as competing risk method.
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First 6 months post-transplant
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Time to Platelet Absolute Neutrophil Recovery (Engraftment)
기간: First 6 months post-transplant
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Estimated using Kaplan-Meier method.
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First 6 months post-transplant
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Treatment Related Mortality Defined as Death in Continuous or Complete Remission
기간: From the date of transplant to the date of death, assessed up to 6 months post transplant
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Based on National Cancer Institute (NCI) CTCAE version 4.
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From the date of transplant to the date of death, assessed up to 6 months post transplant
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Grade III and IV Non Hematologic Toxicities
기간: First 6 months post transplant
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Based on NCI CTCAE version 4.
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First 6 months post transplant
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2차 결과 측정
결과 측정 |
기간 |
|---|---|
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전반적인 생존
기간: 이식 후 최대 2년
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이식 후 최대 2년
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Incidence of Myeloma Progression
기간: Time to the first observation of disease progression/relapse post transplant, assessed up to 2 years post transplant
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Time to the first observation of disease progression/relapse post transplant, assessed up to 2 years post transplant
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Incidence of Transplant Related Mortality and Morbidity
기간: Up to 2 years post transplant
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Up to 2 years post transplant
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Incidence of TTP
기간: Up to 2 years post transplant
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Up to 2 years post transplant
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Incidence of SOS
기간: Up to 2 years post transplant
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Up to 2 years post transplant
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Incidence and Severity of Chronic GVHD
기간: Up to 2 years post transplant
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Up to 2 years post transplant
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Incidence of Opportunistic Infections Including CMV, HSV, and EBV Reactivation
기간: Weekly to day 100
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Weekly to day 100
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Progression Free Survival
기간: From the day of transplant to progression, death, or last contact, assessed up to 2 years
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From the day of transplant to progression, death, or last contact, assessed up to 2 years
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Recovery of T-cell, B Cell and NK Cell Phenotypes
기간: Days 30, 60, 90, and at 6 months after transplant
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Days 30, 60, 90, and at 6 months after transplant
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공동 작업자 및 조사자
수사관
- 수석 연구원: Zaid Al-Kadhimi, Barbara Ann Karmanos Cancer Institute
연구 기록 날짜
연구 주요 날짜
연구 시작
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- 2011-151
- NCI-2012-00120 (레지스트리 식별자: CTRP (Clinical Trial Reporting Program))
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