Phase I/II Trial of Allogeneic Peripheral Blood Stem Cell Transplantation Followed by Maintenance Therapy With Lenalidomide and Sirolimus in Patients With High-Risk Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Phase I: Number of Participants With Dose Limiting Toxicity
研究概览
简要总结
One of the complications that can occur after a stem cell transplant is called graft versus host disease (GVHD). Another complication is that multiple myeloma may come back (relapse). In this study, a drug called lenalidomide will be started 1-2 months after a transplant, or possibly later depending on recovery of your side effects. Lenalidomide and sirolimus have been shown to work together against multiple myeloma. Therefore, lenalidomide will be combined with sirolimus with the hope that this will help prolong the amount of time the disease is in remission. Researchers hope these steps will help prolong the amount of time the multiple myeloma is in remission and will decrease the chance of 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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Understand and voluntarily sign an informed consent form.
- •Age 18-70 years at the time of signing the informed consent form.
- •Able to adhere to the study visit schedule and other protocol requirements.
- •Previously documented multiple myeloma (MM) with measurable monoclonal protein by either serum/urine protein electrophoresis or serum free light chains, or measurable plasmacytomas.
- •ECOG performance status of 0-2 at study entry (see Appendix 2).
- •Acceptable organ function as outlined in the protocol.
- •Otherwise fitting institutional criteria for allogeneic stem cell transplantation.
- •Presence of an HLA-matched (5/6 or 6/6 matched for HLA-A, B, and DR) sibling donor, or a HLA-matched (matched for at least HLA-A, B, C, and DRB1) unrelated donor by high-resolution testing.
- •Disease free of prior malignancies for >/= 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix or breast.
- •All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
- •Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test
排除标准
- •Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
- •Pregnant or breast feeding females.
- •Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
- •Known hypersensitivity to thalidomide or Lenalidomide.
- •The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
- •Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine or prior infection to which they are now immune (i.e., not carriers) are eligible.
- •Donor Inclusion Criteria:
- •The following categories of donor will be acceptable:
- •HLA-matched related donor (5/6 or 6/6 match): Minimal typing necessary is serologic typing for class I (A, B) and molecular typing for class II (DRB1).
- •HLA-matched Unrelated Donor (MUD): Molecular identity at least at HLA A, B, C, and DRB1 and DQB1 (8/10 match) by high resolution typing is required.
- •Syngeneic donors are not eligible.
- •The donor must be healthy and must be an acceptable donor as per institutional standards for marrow or stem cell donation.
- •Age ≥ 18 years
研究组 & 干预措施
Open Label, Single Arm
Use sirolimus and tacrolimus as GvHD prophylaxis with sirolimus and lenalidomide as post-transplant maintenance
干预措施: Sirolimus (Drug)
Open Label, Single Arm
Use sirolimus and tacrolimus as GvHD prophylaxis with sirolimus and lenalidomide as post-transplant maintenance
干预措施: Tacrolimus (Drug)
Open Label, Single Arm
Use sirolimus and tacrolimus as GvHD prophylaxis with sirolimus and lenalidomide as post-transplant maintenance
干预措施: Lenalidomide (Drug)
结局指标
主要结局
Phase I: Number of Participants With Dose Limiting Toxicity
时间窗: 28 days
The number of patients who had a DLT during the dose finding/confirming portion (Phase I) of the trial for the safety of the combination of sirolimus, tacrolimus and lenalidomid. Patients will be monitored for 28 days (a cycle) to determine whether a DLT is experienced for the specific dose level.
Phase II: Percent of Patients Alive and Free of Progression at 12 Months Following Transplant
时间窗: Transplant (Day 0) through 1 year post-transplant
Percent of patients and the 95% Binomial Confidence interval who were alive and free of progression at 12 months following transplant for the patients in Phase II. Progression will be based on International Myeloma Working Group criteria where patients may meet any one of the following criteria - increase of 25% or more in serum or urine M-protein from baseline, Serum M-protein and/or the absolute increase must be \>=0.5 g/dl, Urine M-protein and/or absolute increase must be \>=200 mg/24 hours, development of new bone lesions or soft tissue plasmacyomas or definite increase in the size of existing bone lesions or soft tissue plasmacyomas, or development of hypercalcemia (corrected serum Ca++\>11.5 mg/dl) that can be attributed solely to plasma cell proliferative disease.
次要结局
- Phase II - Percent of Patients With Treatment-related Deaths at 100 Days(100 days post transplant)
- Phase II - Percent of Patients With Treatment-related Deaths at 1 Year(Transplant (Day 0) through 1 year post-transplant)
- Phase II - Time to Platelet Engraftment(Transplant (Day 0) through 1 year post-transplant)
- Phase II - Percent of Patients With Acute Graft Versus Host Disease (GvHD)(Day 0 through 1 year post transplantation)
- Phase II - Percent of Patients With Chronic Graft Versus Host Disease (GvHD)(Transplant (Day 0) through 1 year post-transplant)
- Phase II - Time to Neutrophil Engraftment(Transplant (Day 0) through 1 year post transplant)
研究者
Sherif S. Farag
Professor of Medicine
Indiana University