NCT02447055撤回早期 1 期
Allogeneic Stem Cell Transplantation for Patients With Multiple Myeloma: a Pilot Feasibility Study Using a Novel Protocol
适应症
干预措施
相关药物
试验速览
- 阶段
- 早期 1 期
- 状态
- 撤回
- 主要终点
- Safety and tolerability of regimen as measured by grade and frequency of adverse events
研究概览
简要总结
The purpose of this study is to develop a novel platform for allo-SCT in multiple myeloma (MM) with the idea of maximizing anti-myeloma effect with conditioning and minimizing GvHD (graft versus host disease). Specifically, the investigators will use the Flu/Mel (fludarabine and melphalan) regimen. For GvHD prophylaxis, the investigators use the Hopkins PT-Cy (post-transplant cyclophosphamide) platform with the novelty of adding tocilizumab as both an anti-myeloma therapy and as a method to reduce GvHD. IL-6 has an important role in promoting the growth of myeloma cells and progression of disease.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed diagnosis of myeloma.
- •Between 18 and 70 years of age (inclusive).
- •Karnofsky performance status ≥ 50% or ECOG performance score of ≤ 2 -Completion of last anti-myeloma therapy (if any) must occur at least 14 days before conditioning.
- •Must have an HLA-matched sibling, HLA-matched unrelated donor, or a related haploidentical donor:
- •Available HLA-matched sibling or unrelated donor must meet the following criteria:
- •At least 18 years of age
- •HLA donor/recipient match based on at least low-resolution typing per institutional standards (syngeneic donors [identical twins] are excluded)
- •In the investigator's opinion, is in general good health, and medically able to tolerate leukapheresis required for harvesting stem cells
- •No active hepatitis
- •Negative for HTLV and HIV
- •Not pregnant
- •Available haploidentical donor must meet the following criteria:
- •Blood-related family member (sibling (full or half), offspring, parent, cousin, niece or nephew, aunt or uncle, or grandparent)
- •At least 18 years of age
- •HLA-haploidentical donor/recipient match by at least low-resolution typing per institutional standards
- •In the investigator's opinion, is in general good health, and medically able to tolerate leukapheresis required for harvesting stem cells
- •No active hepatitis
- •Negative for HTLV and HIV
- •Not pregnant
- •Normal bone marrow and organ function as defined below within 14 days prior to first study drug dose (conditioning regimen):
- •Total bilirubin ≤ 2.5 mg/dl
- •AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN
- •Creatinine ≤ 2.0 x ULN OR estimated creatinine clearance ≥ 30 mL/min/1.73 m2 by Cockcroft-Gault Formula (See Appendix C)
- •Oxygen saturation ≥ 90% on room air
- •LVEF ≥ 40%
- •FEV1 and FVC ≥ 40% predicted, DLCOc ≥ 40% predicted
- •Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry through Day +100 visit. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- •Able to understand and willing to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
排除标准
- •Receiving renal replacement therapy, hemodialysis, or peritoneal dialysis.
- •Presence of another concurrent malignancy requiring treatment.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to melphalan, cyclophosphamide, or other agents used in the study.
- •Presence of an uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Pregnant and/or breastfeeding.
- •Previous treatment with tocilizumab (TCZ).
- •Immunization with a live/attenuated vaccine within 28 days prior to conditioning.
- •Any history of recent serious bacterial, viral, fungal, or other opportunistic infections, precluding a stem cell transplant according to the treating physician.
- •Serologic evidence of HIV
- •Active infection with Hepatitis A, B, or C. Active infection is defined as serologic positivity and elevated liver function tests.
- •History of tuberculosis
- •Active infection with EBV as defined as EBV viral load ≥ 10,000 copies per mL of whole blood; EBV viral load testing is only required if the patient has clinical signs or symptoms suggestive of active EBV infection
- •Active infection with CMV as defined as CMV viral load ≥ 10,000 copies per mL of whole blood; CMV viral load testing is only required if the patient has clinical signs or symptoms suggestive of active CMV infection
- •History of complicated diverticulitis, including fistulae, abscess formation or gastrointestinal (GI) perforation.
- •Pre-existing CNS demyelination or seizure disorders
- •Major surgery within preceding 8 weeks
- •Body weight >150kg
- •History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies.
研究组 & 干预措施
Arm 1 (Flu/Mel/PT-Cy & Tac/MMF for certain cases)
Experimental
- Fludarabine 30 mg/m^2 intravenously (IV) on Days -5, -4, -3, and -2
- Melphalan 140 mg/m^2 IV on Day -2
- Tocilizumab 8 mg/m^2 (capped at 800 mg) IV on Day -1
- Stem cell infusion on Day 0
- Cyclophosphamide 50 mg/kg IV on Days +3 and +4
- Tacrolimus 1 mg/day IV on Day +5 (for unrelated & haploidentical cases)
- Mycophenolate mofetil 15 mg/kg orally three times per day on Day +5 (for unrelated & haploidentical cases)
- Filgrastim 10 ug/kg/day subcutaneously until neutrophil recovery starting on Day +5
干预措施: Tocilizumab (Biological)
Arm 1 (Flu/Mel/PT-Cy & Tac/MMF for certain cases)
Experimental
- Fludarabine 30 mg/m^2 intravenously (IV) on Days -5, -4, -3, and -2
- Melphalan 140 mg/m^2 IV on Day -2
- Tocilizumab 8 mg/m^2 (capped at 800 mg) IV on Day -1
- Stem cell infusion on Day 0
- Cyclophosphamide 50 mg/kg IV on Days +3 and +4
- Tacrolimus 1 mg/day IV on Day +5 (for unrelated & haploidentical cases)
- Mycophenolate mofetil 15 mg/kg orally three times per day on Day +5 (for unrelated & haploidentical cases)
- Filgrastim 10 ug/kg/day subcutaneously until neutrophil recovery starting on Day +5
干预措施: Melphalan (Drug)
Arm 1 (Flu/Mel/PT-Cy & Tac/MMF for certain cases)
Experimental
- Fludarabine 30 mg/m^2 intravenously (IV) on Days -5, -4, -3, and -2
- Melphalan 140 mg/m^2 IV on Day -2
- Tocilizumab 8 mg/m^2 (capped at 800 mg) IV on Day -1
- Stem cell infusion on Day 0
- Cyclophosphamide 50 mg/kg IV on Days +3 and +4
- Tacrolimus 1 mg/day IV on Day +5 (for unrelated & haploidentical cases)
- Mycophenolate mofetil 15 mg/kg orally three times per day on Day +5 (for unrelated & haploidentical cases)
- Filgrastim 10 ug/kg/day subcutaneously until neutrophil recovery starting on Day +5
干预措施: Fludarabine (Drug)
Arm 1 (Flu/Mel/PT-Cy & Tac/MMF for certain cases)
Experimental
- Fludarabine 30 mg/m^2 intravenously (IV) on Days -5, -4, -3, and -2
- Melphalan 140 mg/m^2 IV on Day -2
- Tocilizumab 8 mg/m^2 (capped at 800 mg) IV on Day -1
- Stem cell infusion on Day 0
- Cyclophosphamide 50 mg/kg IV on Days +3 and +4
- Tacrolimus 1 mg/day IV on Day +5 (for unrelated & haploidentical cases)
- Mycophenolate mofetil 15 mg/kg orally three times per day on Day +5 (for unrelated & haploidentical cases)
- Filgrastim 10 ug/kg/day subcutaneously until neutrophil recovery starting on Day +5
干预措施: Cyclophosphamide (Drug)
Arm 1 (Flu/Mel/PT-Cy & Tac/MMF for certain cases)
Experimental
- Fludarabine 30 mg/m^2 intravenously (IV) on Days -5, -4, -3, and -2
- Melphalan 140 mg/m^2 IV on Day -2
- Tocilizumab 8 mg/m^2 (capped at 800 mg) IV on Day -1
- Stem cell infusion on Day 0
- Cyclophosphamide 50 mg/kg IV on Days +3 and +4
- Tacrolimus 1 mg/day IV on Day +5 (for unrelated & haploidentical cases)
- Mycophenolate mofetil 15 mg/kg orally three times per day on Day +5 (for unrelated & haploidentical cases)
- Filgrastim 10 ug/kg/day subcutaneously until neutrophil recovery starting on Day +5
干预措施: Tacrolimus (Drug)
Arm 1 (Flu/Mel/PT-Cy & Tac/MMF for certain cases)
Experimental
- Fludarabine 30 mg/m^2 intravenously (IV) on Days -5, -4, -3, and -2
- Melphalan 140 mg/m^2 IV on Day -2
- Tocilizumab 8 mg/m^2 (capped at 800 mg) IV on Day -1
- Stem cell infusion on Day 0
- Cyclophosphamide 50 mg/kg IV on Days +3 and +4
- Tacrolimus 1 mg/day IV on Day +5 (for unrelated & haploidentical cases)
- Mycophenolate mofetil 15 mg/kg orally three times per day on Day +5 (for unrelated & haploidentical cases)
- Filgrastim 10 ug/kg/day subcutaneously until neutrophil recovery starting on Day +5
干预措施: Mycophenolate mofetil (Drug)
Arm 1 (Flu/Mel/PT-Cy & Tac/MMF for certain cases)
Experimental
- Fludarabine 30 mg/m^2 intravenously (IV) on Days -5, -4, -3, and -2
- Melphalan 140 mg/m^2 IV on Day -2
- Tocilizumab 8 mg/m^2 (capped at 800 mg) IV on Day -1
- Stem cell infusion on Day 0
- Cyclophosphamide 50 mg/kg IV on Days +3 and +4
- Tacrolimus 1 mg/day IV on Day +5 (for unrelated & haploidentical cases)
- Mycophenolate mofetil 15 mg/kg orally three times per day on Day +5 (for unrelated & haploidentical cases)
- Filgrastim 10 ug/kg/day subcutaneously until neutrophil recovery starting on Day +5
干预措施: Filgrastim (Drug)
结局指标
主要结局
Safety and tolerability of regimen as measured by grade and frequency of adverse events
时间窗: Day +100
Adverse events will be graded using NCI CTCAE v4.0 and summarized by grade and frequency
次要结局
- Time to platelet engraftment(Day +100)
- Cumulative incidence and severity of acute GvHD(6 months)
- Cumulative incidence and severity of chronic GvHD(1 year)
- Non-relapse mortality (NRM)(Day +180)
- Progression-free survival (PFS)(1 year)
- Overall survival (OS)(1 year)
- Time to neutrophil engraftment(Day +30)
研究者
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