NCT06107738招募中2 期
IBEX: Phase 2 Trial of Iberdomide + SQ Daratumumab as Post-Autologous Stem Cell Transplant Maintenance Therapy in Multiple Myeloma
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 3
- 主要终点
- Rate of MRD (-) at 12 months
研究概览
简要总结
The goal of this phase 2 clinical trial is to learn if patients with Multiple Myeloma who are minimal residual disease positive after initial therapy (including an autologous stem cell transplant [ASCT]) will benefit from maintenance therapy with Iberdomide and subcutaneous (SC) Daratumumab. The main questions it aims to answer are:
- Assess if giving Iberdomide and the SC Daratumumab in the maintenance setting is an effective treatment and warrants further investigation in patients with residual disease
- Is giving Iberdomide and SC Daratumumab maintenance post ASCT a safe option
Participants will:
- provide informed consent and complete screening assessments for eligibility within 28 days of starting treatment
- Screening assessments include specific laboratory tests, a medical history assessment and a physical examination (including temperature, pulse, blood pressure, respirations, height and weight), an assessment of your heart function, a breathing test, cancer imaging, a bone marrow biopsy, minimal residual disease testing (MRD) and a questionnaire
- If eligible, patients will start treatment with Iberdomide (1.0 mg on day 1-21 of each 28 day cycle, with an increase to 1.3 mg on Cycle 4 if the 1.0 mg dose was tolerated, to a maximum of 26 cycles or progressive disease, whichever is first) and SC Daratumumab (1800 mg SC on days 1, 8, 15 and 22 of cycle 1 and 2, then 1800 mg SC on Day 1 and 15 of cycle 3-6 and 1800 mg SC on Day 1 for cycles 7-26 to a maximum of 26 cycles or progressive disease, whichever is first)
- while receiving treatment on study, physical exams (including temperature, pulse, blood pressure, respirations, height and weight), toxicity assessments, laboratory assessments and questionnaires will be done at various times over the course of the 26 cycles
- an MRD assessment is required at 6, 12 and 24 months after starting treatment
- End of treatment will occur once 26 cycles are completed, or cancer has progressed whichever comes first. At that time, specific laboratory tests, a physical examination (including temperature, pulse, blood pressure, respirations, height and weight), cancer imaging, a bone marrow biopsy and minimal residual disease testing (MRD) will occur.
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
- •1. Multiple Myeloma patients who have received prior DARA-containing induction therapy and have attained at least a partial response.
- •2. Patients who have completed Autologous Stem Cell Transplant (ASCT) 90-150 days prior to registration, without any post-ASCT therapy and without post-ASCT disease progression (according to IMWG criteria)
- •3. Patients who are Minimal Residual Disease positive (MRD (+)) as measured by the ClonoSEQ assay using a sensitivity of 10-5, measured 90-150 days following ASCT.
- •4. Prior DARA-containing induction therapy (at least 3 cycles), attaining at least a partial response.
- •5. Completed ASCT within 90-150 days prior to registration, without any post-ASCT therapy and without evidence of post-ASCT disease progression (according to IMWG criteria)
- •6. MRD (+) at the time of study enrollment using the clonoSEQ NGS (next-generation sequencing) assay. Patients with an M-spike of ≥ 0.5 g/dL and/or an abnormal free light chain ratio (with an involved serum free light chain of ≥ 10 mg/dL) at enrollment are considered MRD (+) and do not require baseline MRD testing if they have previously had this testing done with successful clonality assessment.
- •7. ECOG (Eastern Cooperative Oncology Group) Performance Status \/= 75,000/mm3, hemoglobin \>/= 8 g/dL, and ANC (absolute neutrophil count) \>/= 1,000/mm3 within 28 days prior to registration. NOTE: transfusion to achieve the hemoglobin threshold IS permissible.
- •9. Adequate hepatic function defined by the following within 28 days prior to registration: total bilirubin \/= 30 mL/min., as measured by a 24-hour urine collection or estimated by the Cockcroft and Gault formula within 28 days prior to registration.
- •11. All ASCT-related toxicities must have recovered to \
排除标准
- •Active HIV, or HCV (defined as detectable viremia for any of these conditions).
- •Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen[HBsAg]). Patients with resolved infection (i.e., patients who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time PCR (polymerase chain reaction) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded.
- •EXCEPTION: Patients with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR
- •Unable to assess MRD status at entry or is MRD(-) at 10-5 threshold at entry
- •Heart attack or stroke within 90 days of study enrollment
- •Unable to tolerate required anti-thrombotic or anti-viral prophylaxis
- •Major surgery within 28 days of enrollment
- •Medical, neurologic, or psychiatric condition which renders patient unable to safely comply with study therapy and schedule requirements (including, but not limited to, unstable angina, New York Heart Association Class III-IV congestive heart failure, or uncontrolled cardiac arrhythmia)
- •Intolerance of prior DARA therapy (requiring discontinuation of DARA previously due to toxicity)
- •A history of malignancy (other than multiple myeloma) unless all treatment of that malignancy was completed at least 2 years before consent and the patient has no evidence of disease before the date of enrollment. Exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years.
- •Be exhibiting clinical signs of meningeal or central nervous system involvement due to multiple myeloma.
- •Have known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal.
- •Have known moderate or severe persistent asthma within the past 2 years (see Section 9.2.4), or current uncontrolled asthma of any classification. Note that patients who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study, provided that FEV1 is ≥50% of predicted normal.
- •Note: pursuant to exclusion criteria (k) and (l), FEV1 testing is required for patients with suspected COPD or asthma. Patients with FEV1 <50% of predicted normal (or for patients ≥65 years of age, old FEV1 <50% or diffusing capacity of the lung [DLCO] <50%) on screening assessment must be excluded.
- •Have any of the following:
- •Myocardial infarction within 6 months of enrollment, or an unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure, New York Heart Association Class III-IV),
- •Uncontrolled cardiac arrhythmia
- •Have known allergies, hypersensitivity, or intolerance to boron or mannitol, sorbitol, corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to the IB) or known sensitivity to lenalidomide, thalidomide, or pomalidomide.
- •Be pregnant, or breast-feeding, or planning to become pregnant or breast-feed while enrolled in this study or within 90 days after the last dose of study treatment(s). Or, if male, planning to father a child while enrolled in this study or within 90 days after the last dose of study treatment(s).
- •Prolongation of QT interval on screening ECG as defined by a QTc interval > 470 msec using Fridericia's QT correction formula.
- •Use of strong inhibitors or inducers of CYP3A4, P-gp, or BCRP for at least 14 days or 5 half-lives (whichever is shorter) prior to initiating protocol therapy.
研究组 & 干预措施
Iberdomide and Daratumumab
Experimental
干预措施: Daratumumab/rHuPH20 Co-formulation (Drug)
Iberdomide and Daratumumab
Experimental
干预措施: Iberdomide (Drug)
结局指标
主要结局
Rate of MRD (-) at 12 months
时间窗: 12 months
Summarized by a binomial response rate and its associated 2-sided 90% confidence interval (CI) using Pearson-Klopper method.
次要结局
- Rate of Sustained MRD (-)(24 months)
- Progression Free Survival(24 months)
- Overall Survival(24 months)
- Rate on Improvement in IMWG response category(24 months)
- Progression-Free Survival(12 months)
- Patient reported Quality of Life (QoL) per EORTC QLQ-C30(At baseline and day 1 of each treatment cycle until end of treatment)
- Frequency of treatment interruptions and dosage adjustments during maintenance(24 months)
- Patient reported Quality of Life (QoL) per EQ-5D-5L(At baseline and day 1 of each treatment cycle until end of treatment)
- Overall Survival(12 months)
研究者
Jeffrey Zonder
Principal Investigator, Multiple Myeloma Multidisciplinary team leader
Barbara Ann Karmanos Cancer Institute
研究点 (3)
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