A Phase II Study to Assess the Efficacy of Maraviroc in Prophylaxis of GVHD in Patients With Hematologic Malignancies Undergoing Reduced-Intensity Allogeneic SCT From Unrelated Donors
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Day +180 Rate of Grade II-IV Acute GVHD
研究概览
简要总结
RATIONALE: Successful allogeneic stem-cell transplantation is often limited by graft-versus-host disease (GVHD). Migration of donor cells into tissues plays a major role in GVHD. Drugs that block chemokine receptors such as CCR5, can potentially decrease the migration of donor cells into tissues. Blocking CCR5 after allogeneic stem-cell transplantation may therefore reduce the rates of GVHD.
PURPOSE: This study explores the efficacy of pharmacologic inhibition of CCR5 in prevention of GVHDby administering maraviroc during allogeneic stem-cell transplantation with reduced intensity conditioning.
详细描述
Detailed Description:
PRIMARY OBJECTIVES:
To estimate the cumulative incidence of grade 2-4 acute GVHD by day 180 with the addition of maraviroc to a standard prophylaxis regimen in patients with hematologic malignancies undergoing reduced intensity allogeneic stem-cell transplantation (RIC SCT) from unrelated donors.
SECONDARY OBJECTIVES:
- To assess the toxicity of a prolonged administration of maraviroc in patients undergoing RIC SCT.
- To estimate the rates of severe (grade 3-4) acute GVHD by day 100 and 180, grade 2-4 acute GVHD by day 100, organ-specific acute GVHD, chronic GVHD, relapse, infections, non-relapse mortality, use of immunosuppressive therapies and 1-year survival in patients treated with maraviroc after RIC SCT.
- To assess the effect of treatment with maraviroc on immune recovery, engraftment and donor T-cell chimerism in peripheral blood and in target organs.
- To assess the effect of donor and recipient CCR5 genotype on the incidence of acute GVHD in patients receiving maraviroc as part of a GVHD prophylaxis regimen.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients ≥18 years of age with a hematologic malignancy other than aplastic anemia or primary myelofibrosis, scheduled to undergo RIC allogeneic SCT with a peripheral blood stem cell graft from an unrelated donor, using Flu/Bu conditioning and Tac/MTX GVHD prophylaxis. The following diagnoses are included:
- •Acute leukemia - AML, ALL or acute biphenotypic leukemia. Patients will have documentation of complete remission within 6 weeks prior to their transplant. Complete remission is defined as <5% blasts on a bone marrow biopsy and absence of any known extramedullary disease.
- •Chronic myelogenous leukemia in any stage, but with documentation of <5% blasts on a bone marrow biopsy within 6 weeks prior to transplant.
- •Myelodysplastic syndrome of any subtype, but with documentation of <5% blasts on a bone marrow biopsy within 6 weeks prior to transplant.
- •Myeloproliferative disorders other than primary myelofibrosis.
- •Lymphoma - All types of lymphoma are eligible.
- •CLL and PLL.
- •Patients who meet institutional eligibility criteria for allogeneic SCT:
- •Renal function: Serum creatinine ≤
- •Hepatic function: Baseline direct bilirubin, ALT or AST lower than three times the upper limit of normal.
- •Pulmonary disease: FVC or FEV1 ≥ 40% predicted.
- •Cardiac ejection fraction ≥ 40%.
- •Availability of an unrelated donor, identified and screened by the NMDP. The donor will have at least 7/8 HLA-A, -B, -C and -DRB1 matching by high resolution molecular typing and will meet NMDP eligibility criteria to serve as a peripheral blood stem-cell donor.
- •Karnofsky score ≥ 70% at the time of screening.
- •Capacity to understand and sign the study informed consent form.
- •Negative pregnancy test. Women of childbearing potential (not having had a hysterectomy, a bilateral oophorectomy or bilateral tubal ligation, or be post-menopausal with a total cessation of menses of > 1 year) must agree to use documented reliable method(s) of contraception. Men should agree to use condoms during the study period.
- •Co-enrollment in other clinical trials that do not include experimental GVHD therapies is allowed.
- •Exclusion Criteria
- •Patients with aplastic anemia or primary myelofibrosis. Patients with marrow fibrosis secondary to MDS, AML or a myeloproliferative disorder other than primary myelofibrosis are eligible.
- •Patients who are not expected to be available for follow-up in our institution for at least 180 days after the transplant.
- •Prior allogeneic SCT.
- •Uncontrolled bacterial, viral or fungal infections.
- •Patients who receive maraviroc for the treatment of HIV infection.
- •Patients receiving other investigational drugs for GVHD.
- •Co-enrollment in other clinical trials that do not include experimental GVHD therapies is allowed.
- •Patients with prior malignancies are excluded unless treated with curative intent and known to be free of disease for at least 2 years.
排除标准
- 未提供
研究组 & 干预措施
Maraviroc
Phase II, single arm, single center trial, assessing the efficacy of the combination of tacrolimus, methotrexate and maraviroc as graft-versus-host disease (GVHD) prophylaxis after unrelated donor peripheral blood stem-cell transplantation in patients with hematologic malignancies. Patients enrolled on this trial will receive a standard conditioning regimen with fludarabine and busulfan followed by a peripheral blood stem cell infusion from an unrelated donor, standard GVHD prophylaxis and standard antiviral and antifungal prophylaxis. In addition, all patients will receive maraviroc from day -3 to d+ 90.
干预措施: Maraviroc 300 mg (Drug)
结局指标
主要结局
Day +180 Rate of Grade II-IV Acute GVHD
时间窗: 180 days
The cumulative incidence of grade II-IV acute GVHD by day 180 after the stem-cell infusion. This is based on consensus conference criteria.
次要结局
未报告次要终点