Gemcitabine/Clofarabine/Busulfan and Allogeneic Transplantation for Aggressive Lymphomas
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Optimal Dose of Gemcitabine Hydrochloride Determined by Dose Limiting Toxicity
研究概览
简要总结
This phase I/II trial studies the side effects and best dose of gemcitabine hydrochloride, clofarabine, and busulfan before donor stem cell transplant and to see how well it works in treating patients with B-cell or T-cell non-Hodgkin lymphoma or Hodgkin lymphoma that does not respond to treatment. Giving chemotherapy before a donor bone marrow or peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.
详细描述
PRIMARY OBJECTIVES:
I. To define the maximum tolerated dose (MTD) of infusional gemcitabine (gemcitabine hydrochloride) combined with fixed doses of clofarabine and busulfan in patients with lymphoma receiving an allogeneic stem-cell transplant (alloSCT).
II. To estimate the day +100 success rate, defined as percentage of patients who are alive, engrafted and without grade 3-4 graft-versus (vs.)-host-disease (GVHD).
SECONDARY OBJECTIVES:
I. To estimate the day +100 success rate (defined as percentage of patients who are alive, engrafted and without grade 3-4 graft-vs.-host-disease [GVHD]).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients with refractory B-cell or T-cell non-Hodgkin's lymphoma or Hodgkin's lymphoma who are eligible for allogeneic transplantation
- •An 8/8 human leukocyte antigen (HLA) matched (high resolution typing at A, B, C, DRB1) sibling or unrelated donor
- •Left ventricular ejection fraction (EF) >= 45%
- •Forced expiratory volume in one second (FEV1) >= 50%
- •Forced vital capacity (FVC) >= 50%
- •Diffusing capacity of the lung for carbon monoxide (DLCO) >= 50%
- •Estimated serum creatinine clearance >= 50 ml/min (using the Cockcroft-Gault formula)
- •Serum creatinine =< 1.6 mg/dL
- •Serum bilirubin =< 2 x upper limit of normal
- •Serum glutamate pyruvate transaminase (SGPT) =< 2 x upper limit of normal
- •Voluntary signed Institutional Review Board (IRB)-approved informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
- •Men and women of reproductive potential must agree to follow accepted birth control methods for the duration of the study; female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study; male subject agrees to use an acceptable method for contraception for the duration of the study
排除标准
- •Patient with active central nervous system (CNS) disease
- •Pregnancy (positive beta human chorionic gonadotropin [HCG] test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization) or currently breast-feeding; pregnancy testing is not required for post-menopausal or surgically sterilized women
- •Active hepatitis B, either active carrier (hepatitis B virus surface antigen [HBsAg] +) or viremic (hepatitis B virus [HBV] deoxyribonucleic acid [DNA] >= 10,000 copies/mL, or >= 2,000 IU/mL)
- •Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic hepatitis C or positive hepatitis C serology
- •Human immunodeficiency virus (HIV) infection
- •Active uncontrolled bacterial, viral or fungal infections
- •Exposure to other investigational drugs within 2 weeks before enrollment
- •Grade >= 3 non-hematologic toxicity from previous therapy that has not resolved to =< grade 1
- •Radiation therapy to head and neck (excluding eyes), and internal organs of chest, abdomen or pelvis in the month prior to enrollment
- •Prior whole brain irradiation
- •Prior autologous stem-cell transplant (SCT) in the prior 3 months
研究组 & 干预措施
Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
PREPARATIVE REGIMEN: Patients receive gemcitabine hydrochloride IV over 40-180 minutes on days -6 and -4, clofarabine IV over 1 hour on days -6 to -3, and busulfan IV over 3 hours on days -6 to -3. Patients with matched unrelated donors also receive antithymocyte globulin IV on days -3 to -1 and patients with CD20-positive disease also receive rituximab IV on days -14, -7, 1, and 8.
TRANSPLANT: Patients undergo allogeneic BMT or PBSCT on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously over 24 hours or PO beginning on day -2 for up to 6 months and mycophenolate mofetil IV over 2 hours or PO TID beginning day 0.
干预措施: Allogeneic Bone Marrow Transplantation (Procedure)
Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
PREPARATIVE REGIMEN: Patients receive gemcitabine hydrochloride IV over 40-180 minutes on days -6 and -4, clofarabine IV over 1 hour on days -6 to -3, and busulfan IV over 3 hours on days -6 to -3. Patients with matched unrelated donors also receive antithymocyte globulin IV on days -3 to -1 and patients with CD20-positive disease also receive rituximab IV on days -14, -7, 1, and 8.
TRANSPLANT: Patients undergo allogeneic BMT or PBSCT on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously over 24 hours or PO beginning on day -2 for up to 6 months and mycophenolate mofetil IV over 2 hours or PO TID beginning day 0.
干预措施: Allogeneic Hematopoietic Stem Cell Transplantation (Procedure)
Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
PREPARATIVE REGIMEN: Patients receive gemcitabine hydrochloride IV over 40-180 minutes on days -6 and -4, clofarabine IV over 1 hour on days -6 to -3, and busulfan IV over 3 hours on days -6 to -3. Patients with matched unrelated donors also receive antithymocyte globulin IV on days -3 to -1 and patients with CD20-positive disease also receive rituximab IV on days -14, -7, 1, and 8.
TRANSPLANT: Patients undergo allogeneic BMT or PBSCT on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously over 24 hours or PO beginning on day -2 for up to 6 months and mycophenolate mofetil IV over 2 hours or PO TID beginning day 0.
干预措施: Anti-Thymocyte Globulin (Biological)
Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
PREPARATIVE REGIMEN: Patients receive gemcitabine hydrochloride IV over 40-180 minutes on days -6 and -4, clofarabine IV over 1 hour on days -6 to -3, and busulfan IV over 3 hours on days -6 to -3. Patients with matched unrelated donors also receive antithymocyte globulin IV on days -3 to -1 and patients with CD20-positive disease also receive rituximab IV on days -14, -7, 1, and 8.
TRANSPLANT: Patients undergo allogeneic BMT or PBSCT on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously over 24 hours or PO beginning on day -2 for up to 6 months and mycophenolate mofetil IV over 2 hours or PO TID beginning day 0.
干预措施: Busulfan (Drug)
Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
PREPARATIVE REGIMEN: Patients receive gemcitabine hydrochloride IV over 40-180 minutes on days -6 and -4, clofarabine IV over 1 hour on days -6 to -3, and busulfan IV over 3 hours on days -6 to -3. Patients with matched unrelated donors also receive antithymocyte globulin IV on days -3 to -1 and patients with CD20-positive disease also receive rituximab IV on days -14, -7, 1, and 8.
TRANSPLANT: Patients undergo allogeneic BMT or PBSCT on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously over 24 hours or PO beginning on day -2 for up to 6 months and mycophenolate mofetil IV over 2 hours or PO TID beginning day 0.
干预措施: Clofarabine (Drug)
Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
PREPARATIVE REGIMEN: Patients receive gemcitabine hydrochloride IV over 40-180 minutes on days -6 and -4, clofarabine IV over 1 hour on days -6 to -3, and busulfan IV over 3 hours on days -6 to -3. Patients with matched unrelated donors also receive antithymocyte globulin IV on days -3 to -1 and patients with CD20-positive disease also receive rituximab IV on days -14, -7, 1, and 8.
TRANSPLANT: Patients undergo allogeneic BMT or PBSCT on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously over 24 hours or PO beginning on day -2 for up to 6 months and mycophenolate mofetil IV over 2 hours or PO TID beginning day 0.
干预措施: Gemcitabine Hydrochloride (Drug)
Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
PREPARATIVE REGIMEN: Patients receive gemcitabine hydrochloride IV over 40-180 minutes on days -6 and -4, clofarabine IV over 1 hour on days -6 to -3, and busulfan IV over 3 hours on days -6 to -3. Patients with matched unrelated donors also receive antithymocyte globulin IV on days -3 to -1 and patients with CD20-positive disease also receive rituximab IV on days -14, -7, 1, and 8.
TRANSPLANT: Patients undergo allogeneic BMT or PBSCT on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously over 24 hours or PO beginning on day -2 for up to 6 months and mycophenolate mofetil IV over 2 hours or PO TID beginning day 0.
干预措施: Mycophenolate Mofetil (Drug)
Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
PREPARATIVE REGIMEN: Patients receive gemcitabine hydrochloride IV over 40-180 minutes on days -6 and -4, clofarabine IV over 1 hour on days -6 to -3, and busulfan IV over 3 hours on days -6 to -3. Patients with matched unrelated donors also receive antithymocyte globulin IV on days -3 to -1 and patients with CD20-positive disease also receive rituximab IV on days -14, -7, 1, and 8.
TRANSPLANT: Patients undergo allogeneic BMT or PBSCT on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously over 24 hours or PO beginning on day -2 for up to 6 months and mycophenolate mofetil IV over 2 hours or PO TID beginning day 0.
干预措施: Peripheral Blood Stem Cell Transplantation (Procedure)
Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
PREPARATIVE REGIMEN: Patients receive gemcitabine hydrochloride IV over 40-180 minutes on days -6 and -4, clofarabine IV over 1 hour on days -6 to -3, and busulfan IV over 3 hours on days -6 to -3. Patients with matched unrelated donors also receive antithymocyte globulin IV on days -3 to -1 and patients with CD20-positive disease also receive rituximab IV on days -14, -7, 1, and 8.
TRANSPLANT: Patients undergo allogeneic BMT or PBSCT on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously over 24 hours or PO beginning on day -2 for up to 6 months and mycophenolate mofetil IV over 2 hours or PO TID beginning day 0.
干预措施: Pharmacological Study (Other)
Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
PREPARATIVE REGIMEN: Patients receive gemcitabine hydrochloride IV over 40-180 minutes on days -6 and -4, clofarabine IV over 1 hour on days -6 to -3, and busulfan IV over 3 hours on days -6 to -3. Patients with matched unrelated donors also receive antithymocyte globulin IV on days -3 to -1 and patients with CD20-positive disease also receive rituximab IV on days -14, -7, 1, and 8.
TRANSPLANT: Patients undergo allogeneic BMT or PBSCT on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously over 24 hours or PO beginning on day -2 for up to 6 months and mycophenolate mofetil IV over 2 hours or PO TID beginning day 0.
干预措施: Rituximab (Biological)
Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
PREPARATIVE REGIMEN: Patients receive gemcitabine hydrochloride IV over 40-180 minutes on days -6 and -4, clofarabine IV over 1 hour on days -6 to -3, and busulfan IV over 3 hours on days -6 to -3. Patients with matched unrelated donors also receive antithymocyte globulin IV on days -3 to -1 and patients with CD20-positive disease also receive rituximab IV on days -14, -7, 1, and 8.
TRANSPLANT: Patients undergo allogeneic BMT or PBSCT on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously over 24 hours or PO beginning on day -2 for up to 6 months and mycophenolate mofetil IV over 2 hours or PO TID beginning day 0.
干预措施: Tacrolimus (Drug)
结局指标
主要结局
Optimal Dose of Gemcitabine Hydrochloride Determined by Dose Limiting Toxicity
时间窗: Within 30 days of transplant
Dose limiting toxicity is defined as number of participants experienced grade 3-4 mucositis lasting for more than 3 days at peak severity, grade 3-4 skin toxicity lasting for more than 3 days at peak severity, occurring within 30 days from transplant, or grade 4 nonhematological/noninfectious toxicity.
Number of Participants That Had 100 Day Success Rate Post Transplant
时间窗: 100 days post transplant
Number of participants that are alive, engrafted, without grade 3-4 GVHD within 100 days post transplant.
次要结局
- Overall Survival(Up to 5 years)
- Treatment Related Mortality(Up to 100 days post-transplant)