Daratumumab, Pomalidomide, and Dexamethasone (DPd) in Relapsed/Refractory Light Chain Amyloidosis Patients Previously Exposed to Daratumumab
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 15
- 试验地点
- 4
- 主要终点
- Percentage of Participants With Overall Complete Hematologic Response
研究概览
简要总结
This study will test the hypothesis that in patients with previous daratumumab exposure, combination therapy of daratumumab, pomalidomide, and dexamethasone (DPd) will yield higher complete remission (CR) rates in relapsed/refractory amyloidosis than historical pomalidomide/dexamethasone treatment.
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
- •Diagnosis of primary AL amyloidosis of tissue
- •Relapsed and/or refractory AL amyloidosis
- •Has received daratumumab or Faspro in any prior line of therapy
- •Prior pomalidomide exposure allowed if ≥ PR achieved and no disease progression occurred within 60 days of last dose received
- •Measurable disease
- •Able to give voluntary written consent
- •Eastern Cooperative Oncology Group performance status and/or other performance status 0, 1, or
- •Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet count ≥ 75,000/mm
- •Total bilirubin ≤ 1.5 × the upper limit of the normal range (ULN) (Total bilirubin ≥ 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN.
- •eGFR ≥ 20 mL/min/1.73 m2 (as calculated by Modified Diet in Renal Disease (MDRD) formula)
排除标准
- •Non-AL amyloidosis
- •Clinically overt myeloma
- •Prior exposure to non-daratumumab anti-CD38 monoclonal antibodies.
- •Clinically significant cardiac disease
- •Severe obstructive airway disease
- •Female patients who are lactating or have a positive serum pregnancy test during the screening period
- •Planned high-dose chemotherapy and autologous stem cell transplantation within 6, 28-day treatment cycles after starting on treatment.
- •Failure to have fully recovered (ie, ≤ Grade 1 toxicity) from the reversible effects of prior chemotherapy.
- •Major surgery within 14 days before enrollment.
- •Radiotherapy within 14 days before enrollment.
- •Infection requiring systemic intravenous antibiotic therapy or other serious infection within 14 days before study enrollment. Systemic treatment, within 14 days before the first dose, with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital, see Appendix 11.7), or use of Ginkgo biloba or St. John's wort.
- •Positive for human immunodeficiency virus (HIV), hepatitis B, and hepatitis C
- •Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
研究组 & 干预措施
daratumumab/pomalidomide/dexamethasone
Pomalidomide:
(4mg orally) on days 1-21 of a 28-day cycle
Dexamethasone:
-
20mg IV as premedication on days 1, 8, 15, and 22
-
20mg orally the day after daratumumab dosing for cycles 1-2 of induction
-
40mg IV as premedication on days 1 and 15 on daratumumab treatment days
-
40mg orally on non-daratumumab days (8 and 15) for cycles 3-6
-
20mg on day 1 of every cycle as premedication on daratumumab dosing day 1 in maintenance cycles (cycles 7 and beyond)
-
If you are a subject age 70 and older, the dexamethasone dosing will be reduced by 50% at the time of induction.
Daratumumab:
- 1800mg sub-cutaneously weekly x8 weeks
- 1800mg sub-cutaneously every 2 weeks during induction (cycles 3-6)
- 1800mg sub-cutaneously every 4 weeks cycles 7 and beyond
干预措施: Daratumumab SC (Drug)
daratumumab/pomalidomide/dexamethasone
Pomalidomide:
(4mg orally) on days 1-21 of a 28-day cycle
Dexamethasone:
-
20mg IV as premedication on days 1, 8, 15, and 22
-
20mg orally the day after daratumumab dosing for cycles 1-2 of induction
-
40mg IV as premedication on days 1 and 15 on daratumumab treatment days
-
40mg orally on non-daratumumab days (8 and 15) for cycles 3-6
-
20mg on day 1 of every cycle as premedication on daratumumab dosing day 1 in maintenance cycles (cycles 7 and beyond)
-
If you are a subject age 70 and older, the dexamethasone dosing will be reduced by 50% at the time of induction.
Daratumumab:
- 1800mg sub-cutaneously weekly x8 weeks
- 1800mg sub-cutaneously every 2 weeks during induction (cycles 3-6)
- 1800mg sub-cutaneously every 4 weeks cycles 7 and beyond
干预措施: Pomalidomide (Drug)
daratumumab/pomalidomide/dexamethasone
Pomalidomide:
(4mg orally) on days 1-21 of a 28-day cycle
Dexamethasone:
-
20mg IV as premedication on days 1, 8, 15, and 22
-
20mg orally the day after daratumumab dosing for cycles 1-2 of induction
-
40mg IV as premedication on days 1 and 15 on daratumumab treatment days
-
40mg orally on non-daratumumab days (8 and 15) for cycles 3-6
-
20mg on day 1 of every cycle as premedication on daratumumab dosing day 1 in maintenance cycles (cycles 7 and beyond)
-
If you are a subject age 70 and older, the dexamethasone dosing will be reduced by 50% at the time of induction.
Daratumumab:
- 1800mg sub-cutaneously weekly x8 weeks
- 1800mg sub-cutaneously every 2 weeks during induction (cycles 3-6)
- 1800mg sub-cutaneously every 4 weeks cycles 7 and beyond
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Percentage of Participants With Overall Complete Hematologic Response
时间窗: Follow-up for up to 1 year
Overall complete hematologic response rate will be defined as percentage of participants who achieve Complete Hematologic Response
次要结局
- Time to Hematologic Progression(Follow-up for up to 5 years)
- Duration of Very Good Partial Response (VGPR) or better hematologic response rates(Follow-up for up to 5 years)
- Median estimate of months that participants have Progression Free Survival(Follow-up for up to 5 years)
- Low-dFLC Partial Response Rate (applicable to low-dFLC pt group)(Follow-up for up to 1 year)
- Median number of months of participant's Overall Survival(Follow-up for up to 5 years)
- Percentage of participants with an Organ Response(Follow-up for up to 3 years)
- Time to Complete Hematologic Response(Follow-up for up to 1 year)
- Time until Next Treatment Therapy(Follow-up for up to 5 years)