Reduce Intensity Conditioning (RIC) Allogenic Hematopoietic Stem Cell Transplantation (Allo HSCT) for Patients With Relapsed Multiple Myeloma: A Pilot Study
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- 2-year Progression-free Survival (PFS)
研究概览
简要总结
This phase II trial studies how well a reduced intensity conditioning regimen after donor stem cell transplant works in treating patients with multiple myeloma that has come back (relapsed). Drugs used in chemotherapy, such as cyclophosphamide, tacrolimus, and mycophenolate mofetil, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as daratumumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving a reduce intensity conditioning regimen consisting of cyclophosphamide, tacrolimus, mycophenolate mofetil, and daratumumab after donor stem cell transplant may improve survival and reduce the risk of multiple myeloma coming back.
详细描述
PRIMARY OBJECTIVE:
I. To determine the 2-year progression-free survival (PFS) for haploidentical, matched or mismatched, related or unrelated reduce intensity allogenic hematopoietic stem cell transplantation (allo HSCT) in relapsed multiple myeloma (MM) patients.
SECONDARY OBJECTIVES:
I. To determine 2 year overall survival (OS). II. To determine the cumulative incidence of grade II-IV acute-graft-versushost-disease (aGVHD) at day 100 and 180.
III. To determine the 100 days, 1 year and 2 year cumulative incidence of treatment-related mortality (TRM).
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with a partial response (PR) or better prior to allo-transplantation
- •Relapsed MM with chemo sensitivity disease, with or without prior autologous HSCT
- •First allogenic transplant
- •Donors can be haploidentical, mismatch or matched related or unrelated. Stem cell source will be peripheral blood except for haploidentical where stem cell source will be bone marrow
- •Ejection fraction >= 45%
- •Estimated creatinine clearance greater than 40 mL/minute
- •Diffusion capacity of the lung for carbon monoxide (DLCO) >= 40% (adjusted for hemoglobin)
- •Forced expiratory volume in 1 second (FEV1) >= 50%
- •Total bilirubin < 2 x the upper limit of normal
- •Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) < 2.5 x the upper normal limit
- •Signed informed consent
排除标准
- •Patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin change (POEMS), Waldenstrom macroglobulinemia
- •Uncontrolled bacterial, viral or fungal infection
- •Patients with prior malignancies < 3 years except resected basal cell/squamous cell carcinoma, treated carcinoma in-situ. Other cancers treated with curative intent < 3 years previously will not be allowed unless approved by the principal investigator
- •Female patients who are pregnant or breastfeeding. A negative pregnancy test will be required for all women of child bearing potential
研究组 & 干预措施
Treatment (conditioning regimen, stem cell transplant)
Patients receive fludarabine IV on days -5 to -2 and melphalan IV on days -3 to -2, then undergo stem cell transplantation on day 0. Patients receive cyclophosphamide on days 3 and 4, tacrolimus PO BID or IV starting on day 5, and mycophenolate mofetil IV or PO TID on days 5 to 35. Patients also receive daratumumab IV starting between days 90-150 for up to 1 year. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: Allogeneic Hematopoietic Stem Cell Transplantation (Procedure)
Treatment (conditioning regimen, stem cell transplant)
Patients receive fludarabine IV on days -5 to -2 and melphalan IV on days -3 to -2, then undergo stem cell transplantation on day 0. Patients receive cyclophosphamide on days 3 and 4, tacrolimus PO BID or IV starting on day 5, and mycophenolate mofetil IV or PO TID on days 5 to 35. Patients also receive daratumumab IV starting between days 90-150 for up to 1 year. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: Cyclophosphamide (Drug)
Treatment (conditioning regimen, stem cell transplant)
Patients receive fludarabine IV on days -5 to -2 and melphalan IV on days -3 to -2, then undergo stem cell transplantation on day 0. Patients receive cyclophosphamide on days 3 and 4, tacrolimus PO BID or IV starting on day 5, and mycophenolate mofetil IV or PO TID on days 5 to 35. Patients also receive daratumumab IV starting between days 90-150 for up to 1 year. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: Daratumumab (Biological)
Treatment (conditioning regimen, stem cell transplant)
Patients receive fludarabine IV on days -5 to -2 and melphalan IV on days -3 to -2, then undergo stem cell transplantation on day 0. Patients receive cyclophosphamide on days 3 and 4, tacrolimus PO BID or IV starting on day 5, and mycophenolate mofetil IV or PO TID on days 5 to 35. Patients also receive daratumumab IV starting between days 90-150 for up to 1 year. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: Fludarabine (Drug)
Treatment (conditioning regimen, stem cell transplant)
Patients receive fludarabine IV on days -5 to -2 and melphalan IV on days -3 to -2, then undergo stem cell transplantation on day 0. Patients receive cyclophosphamide on days 3 and 4, tacrolimus PO BID or IV starting on day 5, and mycophenolate mofetil IV or PO TID on days 5 to 35. Patients also receive daratumumab IV starting between days 90-150 for up to 1 year. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: Melphalan (Drug)
Treatment (conditioning regimen, stem cell transplant)
Patients receive fludarabine IV on days -5 to -2 and melphalan IV on days -3 to -2, then undergo stem cell transplantation on day 0. Patients receive cyclophosphamide on days 3 and 4, tacrolimus PO BID or IV starting on day 5, and mycophenolate mofetil IV or PO TID on days 5 to 35. Patients also receive daratumumab IV starting between days 90-150 for up to 1 year. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: Mycophenolate Mofetil (Drug)
Treatment (conditioning regimen, stem cell transplant)
Patients receive fludarabine IV on days -5 to -2 and melphalan IV on days -3 to -2, then undergo stem cell transplantation on day 0. Patients receive cyclophosphamide on days 3 and 4, tacrolimus PO BID or IV starting on day 5, and mycophenolate mofetil IV or PO TID on days 5 to 35. Patients also receive daratumumab IV starting between days 90-150 for up to 1 year. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: Tacrolimus (Drug)
结局指标
主要结局
2-year Progression-free Survival (PFS)
时间窗: From the date of transplant until the date of relapse or date of death from any cause, assessed at 2 years
Patients who do not relapse or die will be censored at the date of last clinical assessment. Kaplan-Meier curves will be generated to estimate the PFS rates at 2 years posttransplant. To evaluate the potential association between patient characteristics and PFS, the log-rank test will be used to compare the PFS curves and Cox proportional hazard regression model will be used to estimate the hazard ratio.
次要结局
- Incidence of Adverse Events(Up to 2 years post-transplant)
- Number of Patients With Grade II-IV Acute Graft-versus Host Disease (GvHD (aGVHD)(Up to 6 weeks)
- 1-year Cumulative Incidence TRM(From the date of transplant to date of death, assessed at 1 year)
- 2-year Cumulative Incidence of TRM(From the date of transplant to date of death, assessed at 2 years)
- Overall Survival (OS)(From the date of transplant to death or last contact date if no death, assessed up to 2 years)
- Rate of Relapse(From the date of transplant to relapse treating death from any cause as a competing risk, assessed up to 2 years)
- 1- Year GVHD-free Relapse-free Survival (GRFS)(From the date of transplant until the date of grade II-IV acute GVHD, chronic GVHD, disease relapse or progression, or death from any cause, whichever occurs first, assessed at 1 year)
- Number of Patients With a Partial Response(Approximately 11 months)
- 100-day Cumulative Incidence of Treatment-related Mortality (TRM)(From the date of transplant to date of death, assessed up to 100 days)
- Overall Response Rate(Up to 2 years post-transplant)
研究者
Srinivas Devarakonda
Principal Investigator
Ohio State University Comprehensive Cancer Center