NCT00119340已完成1 期
Fludarabine and Low-Dose TBI Dose Escalation to Determine the Optimal Regimen for Achieving High Rates Engraftment of Unrelated Donor Peripheral Blood Stem Cell in Patients With Chronic Myeloid Leukemia - A Multi-Center Trial
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 75
- 试验地点
- 3
- 主要终点
- Increase number of patients with donor T-cell chimerism from > 40% to 90% on day 28 post-transplant
研究概览
简要总结
RATIONALE: Giving low doses of chemotherapy, such as fludarabine, and radiation therapy before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after transplant may stop this from happening.
PURPOSE: This phase I/II trial is studying the side effects and best dose of fludarabine, total-body irradiation, and donor stem cell transplant followed by cyclosporine and mycophenolate mofetil and to see how well they work in treating patients with chronic myelogenous leukemia.
详细描述
OBJECTIVES:
Primary
- Determine whether increasing the intensity of a nonmyeloablative conditioning regimen comprising fludarabine and total body irradiation allows achievement of a donor T-cell chimerism level of > 40% on day 28 post-transplantation in 90% or more of patients with chronic myelogenous leukemia undergoing allogeneic peripheral blood stem cell transplantation and immunosuppression comprising cyclosporine and mycophenolate mofetil.
- Determine the feasibility of reducing the day 84 graft rejection rate/graft failure to < 10% in patients treated with this regimen.
- Determine the feasibility of maintaining the incidence of grade 4 acute graft-versus-host disease at < 10% in patients treated with this regimen.
- Determine the feasibility of maintaining the day 200 nonrelapse mortality rate at < 15% in patients treated with this regimen.
Secondary
- Determine the rate of complete cytogenetic remission in patients treated with this regimen.
- Determine the probability of actuarial disease-free survival of patients treated with this regimen.
- Determine the pharmacokinetics of mycophenolate mofetil and fludarabine in these patients.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Diagnosis of chronic myelogenous leukemia (CML), meeting 1 of the following criteria:
- •First or second chronic phase
- •Philadelphia chromosome-positive (Ph+) disease by cytogenetics or fluorescent in situ hybridization (FISH)
- •First accelerated phase, meeting any of the following criteria:
- •More than 10% but < 30% myeloblasts and promyelocytes in bone marrow or peripheral blood
- •Any additional clonal cytogenetic abnormalities
- •Increasing splenomegally
- •Extramedullary tumor
- •WBC, platelet count, or hematocrit pertubations not controlled by therapy with hydroxyurea, interferon, or imatininb mesylate
- •Persistent unexplained fever or bone pain
- •Less than 5% blasts in marrow at time of transplant
- •No blast crisis
- •No other curative therapy exists
- •Received prior imatinib mesylate AND meets ≥ 1 of the following criteria:
- •Hematologic evidence of disease progression
- •Lack of complete hematologic response after 3 months of treatment with imatinib mesylate
- •Cytogenetic evidence of disease progression, defined as an increase in Ph+ cells or BCR/ABL-positive (BCR/ABL+) cells of > 25%
- •Lack of complete cytogenetic remission (no Ph+ cells by cytogenetic analysis or BCR/ABL+ cells by FISH) after 1 year of treatment with imatinib mesylate
- •At least 65% Ph+ cells by cytogenetic analysis or BCR/ABL+ cells by FISH after 6 months of treatment with imatinib mesylate
- •Less than 3-log reduction in BCR/ABL mRNA levels by quantitative polymerase chain reaction (Q-PCR) compared to a standard baseline level after 1 year of treatment with imatinib mesylate
- •Molecular evidence of disease progression, defined as > 1 log increase in BCR/ABL mRNA levels by Q-PCR, detected in 2 samples
- •Experienced adverse events with imatinib mesylate treatment that would preclude further administration of the drug
- •Patient refused further treatment with imatinib mesylate despite lack of disease progression
- •Refused conventional myeloablative allogeneic stem cell transplantation OR at high risk for regimen-related toxicity due to pre-existing medical conditions (for patients < 50 years of age)
- •Unrelated donor available
- •Matched at HLA-A, -B, -C, -DRB1, and -DQB1 by high-resolution typing
- •A single allele* disparity for HLA-A, -B, or -C allowed
- •Negative anti-donor cytotoxic crossmatch
- •Not a marrow donor NOTE: *Patient and donor pairs homozygous at a mismatched allele (e.g., the patient is A*0101 and the donor is A*0201) are considered a two-allele mismatch and are not allowed
- •No CNS involvement with disease that is refractory to intrathecal chemotherapy
- •PATIENT CHARACTERISTICS:
- •Performance status
- •Karnofsky 70-100%
- •Lanksy 50-100% (for pediatric patients)
- •Life expectancy
- •Not specified
- •Hematopoietic
- •See Disease Characteristics
- •No fulminant liver failure
- •No cirrhosis of the liver with evidence of portal hypertension
- •No alcoholic hepatitis
- •No esophageal varices
- •No history of bleeding esophageal varices
- •No hepatic encephalopathy
- •No uncorrectable hepatic synthetic dysfunction evidenced by prolongation of PT
- •No ascites related to portal hypertension
- •No bacterial or fungal liver abscess
- •No biliary obstruction
- •No chronic viral hepatitis AND bilirubin > 3 mg/dL
- 另有 30 项未显示
排除标准
- 未提供
结局指标
主要结局
Increase number of patients with donor T-cell chimerism from > 40% to 90% on day 28 post-transplant
Reduce graft rejection rate to < 10% day 84 post-transplant
Maintain acute graft-vs-host disease (GVHD) incidence of 10%
Maintain nonrelapse mortality incidence of < 15% on day 200 post-transplant
次要结局
- Pharmacokinetics
- Rate of complete cytogenetic remission
- Probability of actuarial disease-free survival
研究者
研究点 (3)
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