A Phase 1/2 Study of CAT-8015 in Adult Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
The primary objectives of this study are to determine the maximum tolerated dose (MTD) or optimal biologic dose (OBD) and safety profile of CAT-8015 in participants with relapsed or refractory advanced B-cell NHL (diffuse large B-cell lymphoma [DLBCL], follicular lymphoma [FL], mantle cell lymphoma [MCL]) or CLL.
详细描述
To determine the maximum tolerated dose (MTD) or optimal biologic dose (OBD) of CAT-8015 in participants with relapsed or refractory advanced B-cell NHL (DLBCL, FL, MCL) or CLL.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization
- •Participants must have histologically confirmed B-cell CLL, including small lymphocytic lymphoma (SLL), DLBCL, MCL, or FL
- •B-cell NHL: a) Have previous confirmation of B-cell NHL b) Participants with DLBCL or MCL, must have relapsed or refractory disease after at least one prior regimen containing rituximab, either alone or in combination, and be ineligible for any available standard line of therapy known to be life-prolonging or life-saving c) Participants with FL, must have relapsed or refractory disease after at least two prior regimens, one of which included rituximab, either alone or in combination, and be ineligible for any available standard line of therapy known to be life-prolonging or life-saving d) Have measurable disease (at least one lesion greater than or equal to (≥) 20 millimeter (mm) in one dimension or ≥ 15 mm in two dimensions as measured by conventional or high resolution [spiral] computed tomography e) Not be a candidate for a hematopoietic stem cell (HSC) or bone marrow transplant
- •B-cell CLL: a) Have previous confirmation of B-cell CLL with a characteristic immunophenotype by flow cytometry b) Have relapsed or refractory disease after at least 2 prior lines of treatment, at least 1 of which must have contained rituximab and be ineligible for any available standard line of therapy known to be life-prolonging or life-saving c) Not be a candidate for an HSC or BM transplant d) Have symptomatic disease that requires treatment
- •Karnofsky Performance Status ≥ 70
- •Life expectancy of ≥ 12 weeks
- •Toxicities from previous cancer therapies must have recovered to Grade less than (<) 2
- •Adequate hematological function defined as: a) Hemoglobin ≥ 9 g/dL b) Absolute neutrophil count ≥ 1500/mm^3 c) Platelet count ≥ 75,000/mm^3
- •Prothrombin time-International Normalized Ratio/Partial thromboplastin time less than or equal to (≤) 1.5 × upper limit of normal (ULN), or for participants on anticoagulation therapy, status within therapeutic range
- •Women of non-child-bearing potential or using effective contraception
- •Male participants with partners of child-bearing potential must be surgically sterile or use a contraceptive method
排除标准
- •Any available standard line of therapy known to be life-prolonging or life-saving
- •Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic, or hormonal therapy for treatment of cancer
- •For CLL participants only, rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy
- •History of allergy or reaction to any component of the CAT-8015
- •Receipt of any chemotherapy or small molecule targeted therapy or any biological- or immunological-based therapies for leukemia or lymphoma within 6 weeks
- •Prior radiation therapy will not be excluded, providing the volume of bone marrow treated is less than 25 percent
- •Any history of prior pseudomonas-exotoxin immunotoxin administration including CAT-8015, CAT-3888, or LMB-2
- •History of other invasive malignancy within 5 years, with some exceptions
- •Evidence of significant active infection requiring antimicrobial, antifungal, antiparasitic or antiviral therapy or for which other supportive care is given
- •Autologous stem cell transplantation within 6 months prior to study entry
- •Allogenic stem cell transplantation or any other organ transplant
- •HIV-positive or AIDS, Hepatitis B or hepatitis C infection as defined by seropositive for hepatitis B (HBsAg) or hepatitis C and elevated liver transaminases
- •Use of immunosuppressive medication other than steroids within 7 days, use of systemic steroids within 7 days before the first dose of CAT-8015 (inhaled and topical corticosteroids are permitted). Participants may take replacement doses of steroids (defined as ≤ 30 mg/day hydrocortisone or the equivalent) if on a stable dose for at least 2 weeks prior to the first dose of CAT-8015
- •Documented current central nervous system involvement by leukemia or lymphoma
- •Pregnancy or lactation, other severe, concurrent diseases
- •Concurrent enrollment in another clinical study
研究组 & 干预措施
CAT-8015 20 microgram per kilogram (mcg/kg)
Participants will receive 20 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation is to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level are possible if an MTD or OBD is not reached by 60 mcg/kg.
干预措施: CAT-8015 20 mcg/kg (Drug)
CAT-8015 30 mcg/kg
Participants will receive 30 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation is to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level are possible if an MTD or OBD is not reached by 60 mcg/kg.
干预措施: CAT-8015 30 mcg/kg (Drug)
CAT-8015 40 mcg/kg
Participants will receive 40 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation is to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level are possible if an MTD or OBD is not reached by 60 mcg/kg.
干预措施: CAT-8015 40 mcg/kg (Drug)
CAT-8015 50 mcg/kg
Participants will receive 50 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation is to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level are possible if an MTD or OBD is not reached by 60 mcg/kg.
干预措施: CAT-8015 50 mcg/kg (Drug)
CAT-8015 60 mcg/kg
Participants will receive 60 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation is to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level are possible if an MTD or OBD is not reached by 60 mcg/kg.
干预措施: CAT-8015 60 mcg/kg (Drug)
结局指标
主要结局
Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
时间窗: From Screening (Day -28) to Post Therapy Day 30
Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.
Number of Participants With Dose Limiting Toxicities (DLTs)
时间窗: Day 1 to end of Cycle 1 (approximately 28 days)
Any Grade 3 or greater, non-hematological toxicity (including capillary leak syndrome \[CLS\] and thrombotic microangiopathy/ hemolytic uremic syndrome (HUS), Grade 3 or higher treatment-related hematologic toxicities and only ≥ Grade 3 thrombotic microangiopathy /HUS constituted a DLT with few exceptions.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
时间窗: From Screening (Day -28) to Post Therapy Day 30
Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An Serious Adverse Event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.
Number of Participants With Electrocardiogram (ECG) Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
时间窗: From Screening (Day -28) to Post Therapy Day 30
Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.
Maximum Tolerated Dose (MTD)
时间窗: Day 1 to end of Cycle 1 (approximately 28 days)
MTD reflects highest dose of drug that did not cause an unacceptable side effect (= Dose Limiting Toxicity \[DLT\]) in more than 30 percent (%) of participants.
Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
时间窗: From Screening (Day -28) to Post Therapy Day 30
Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.
次要结局
- Duration of Objective Response (DOR)(Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment))
- Percentage of Participants With Partial Response (PR)(Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment))
- Time to Response (TTR)(Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment))
- Percentage of Participants With Complete Response (CR)(Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment))
- Duration of Complete Response(Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment))
- Maximum Plasma Concentration (Cmax) of Moxetumomab Pasudotox(Pre-dose and End of infusion on Day 1, 3 and 5 of each cycle; 1, 3 and 6 hour after the end of infusion on Day 1 of each cycle)
- Elimination Half Life (t1/2) of Moxetumomab Pasudotox(Pre-dose and End of infusion on Day 1, 3 and 5 of each cycle; 1, 3 and 6 hour after the end of infusion on Day 1 of each cycle)
- Percentage of Participants With Stable Disease (SD)(Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment))
- Percentage of Participants With Objective Response (OR)(Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment))
- Number of Capillary Leak Syndrome (CLS) Participants With Weight Changes, Albumin, Hypotension, Edema, Hypoxia, and Pulmonary Adverse Events (AEs)(From Screening (Day -28) to Post Therapy Day 30)
- Area Under Concentration-Time Curve From Dosing Extrapolated to Infinity (AUCinf) of Moxetumomab Pasudotox(Pre-dose and End of infusion on Day 1, 3 and 5 of each cycle; 1, 3 and 6 hour after the end of infusion on Day 1 of each cycle)
- Clearance (CL) of Moxetumomab Pasudotox(Pre-dose and End of infusion on Day 1, 3 and 5 of each cycle; 1, 3 and 6 hour after the end of infusion on Day 1 of each cycle)
- Number of Participants With Positive Anti-Drug Antibody(Baseline (Day 1) up to End of the Treatment (Last dose of Last cycle) (approximately 3 years))
- Duration of Stable Disease (SD)(Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment))
- Number of Participants With CD22 Expression Levels(Baseline (Day 1) up to End of the Treatment (Last dose of Last cycle) (approximately 3 years))