Single-Arm, Open Label, Interventional Phase II Clinical Trial Evaluating MGTA-456 in Patients With High-Risk Malignancy
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Neutrophil Recover
研究概览
简要总结
This is an single arm, open label, interventional phase II trial evaluating the efficacy of umbilical cord blood (UCB) hematopoietic stem and progenitor cells (HSPC) expanded in culture with stimulatory cytokines (SCF, Flt-3L, IL-6 and thromopoietin) on lympho-hematopoietic recovery. Patients will receive a uniform myeloablative conditioning and post-transplant immunoprophylaxis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 55 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age, Unit Cell Dose and HLA Match Criteria
- •Subjects must be ≤55 years of age
- •Subjects must weigh >11 kg
- •Subjects must have a partially HLA matched UCB unit with a pre-cryopreserved TNC dose >1.0 x 107 per kilogram recipient weight. HLA matching is initially based on a minimum of 5 of 8 HLA alleles at high resolution A, B, C, DRB1 typing; searches will be performed according to the current Magenta Cord Blood Search Algorithm.
- •Eligible Diseases:
- •Acute myelogenous leukemia (AML) in morphological complete remission with:
- •Minimal residual disease (MRD) by flow cytometry, or
- •Intermediate to high risk leukemia in first (CR1) based on institutional criteria, eg. not favorable risk AML which is defined as having one of the following:
- •t(8,21) without cKIT mutation
- •inv(16) or t(16;16) without cKIT mutation
- •Normal karyotype with mutated NPM1 but FLT3-ITD wild type
- •Normal karyotype with double mutated CEBPA
- •Acute promyelocytic leukemia (APL) in first molecular remission at the end of consolidation
- •Any second or subsequent CR, or
- •Secondary AML with prior malignancy that has been in remission for at least 12 months.
- •Acute lymphocytic leukemia (ALL) at the following stages:
- •High risk first morphological, cytogenetic and molecular CR with:
- •MRD by flow cytometry, or
- •Diagnosis of Philadelphia chromosome (Ph)+ ALL, or
- •MLL rearrangement at diagnosis with slow early response at Day 14, or
- •Hypodiploidy (< 44 chromosomes or DNA index < 0.81) at diagnosis, or
- •End of induction M3 bone marrow, or
- •End of induction M2 with M2-3 at Day
- •High risk second CR based on institutional criteria (eg, for children, bone marrow relapse <36 months from induction or T-lineage bone marrow relapse or very early isolated central nervous system (CNS) relapse <6 months from diagnosis, or slow re-induction (stage M2-3 at day 28 after induction) regardless of length remission. All patients with MRD by flow cytometry.
- •Any third or subsequent CR.
- •Secondary ALL
- •Biphenotypic/undifferentiated leukemia in morphological, cytogenetic and molecular CR .
- •Chronic Myelogenous Leukemia (CML) in high risk first chronic phase (failure of two tyrosine kinase inhibitors (TKI) or TKI intolerance), accelerated phase or second chronic phase.
- •Myelodysplasia (MDS) IPSS Int-2 or High risk (i.e. RAEB, RAEBt <5% blasts) or other high risk features, including multiple cytopenias, high risk cytogenetics or lack of response to standard therapy..
- •Relapsed large-cell lymphoma, mantle-cell lymphoma and Hodgkin lymphoma that is chemotherapy sensitive and ineligible for an autologous transplant.
- •Burkitt's lymphoma in CR2 or subsequent CR.
- •Relapsed T-cell lymphoma that is chemotherapy sensitive in CR/PR that is ineligible for an autologous transplant.
- •Organ Specific Inclusion Criteria
- •Karnofsky score ≥70 (16 years and older), Lansky play score >50 (children 2-16 years, or 'adequate' score for children <2 years, as detailed in Appendix II.
- •Adequate organ function defined as:
- •Renal: Serum creatinine within normal range for age, or if serum creatinine outside normal range for age, then creatinine clearance >40 ml/min or GFR ≥70 mL/min/1.73 m2.normal for age
- •Hepatic: Bilirubin <3x upper limit of normal (ULN) and AST, ALT and alkaline phosphatase <5x ULN.
- •Pulmonary function: DLCO, FEV1, FEC (diffusion capacity) >5030% of predicted (corrected for hemoglobin); if unable to perform pulmonary function tests, then O2 saturation >95% on room air.
- •Cardiac: No uncontrolled arrhythmia and left ventricular ejection fraction at rest must be >3545%.
- •Available 'back-up' HSPC graft (e.g, second UCB unit, haploidentical related donor).
- •Females of child bearing potential and sexually active males must agree to use adequate birth control during study treatment.
- •Voluntary written consent signed (adult or parental) before performance of any study-related procedure not part of normal medical care.
排除标准
- •Patients with a HLA matched sibling donor or a HLA matched unrelated donor who is available for marrow or peripheral blood stem cell collection at the desired time of transplant.
- •Pregnant or breast feeding. The agents used in this study may be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. Females of childbearing potential must have a blood test or urine study within 14 days prior to study enrollment to rule out pregnancy.
- •Evidence of human immunodeficiency virus (HIV) infection or known HIV positive serology.
- •Active bacterial, viral or fungal infection (currently taking medication and persistence of clinical signs and symptoms) with a minimum of 4 weeks of anti-fungal treatment
- •Prior autologous or allogeneic transplant.
- •Other active malignancy.
- •Subjects >2 3 years of age unable to receive TBI 1320 cGy due to extensive prior therapy including >12 months alkylator therapy or >6 months alkylator therapy with extensive radiation, or prior Y-90 ibritumomab (Zevalin) or I-131 tostumomab (Bexxar), as part of their salvage therapy.
研究组 & 干预措施
FLU, CY, TBI + MGTA-456 infusion
All patients will receive MGTA-456 on the day of transplantation after myeloablative conditioning.
All patients aged 3-55 years will be conditioned with cyclophosphamide (CY) 120 mg/kg total dose, fludarabine (FLU) 75 m/m2 total dose and total body irradiation (TBI) 1320 cGy total dose as well as tacrolimus (Tac) and mycophenolate mofetil (MMF) immunoprophylaxis and granulocyte-colony stimulating factor (G-CSF)
干预措施: Granulocyte Colony-Stimulating Factor (G-CSF) (Drug)
BU,FLU, MEL + MGTA-456 infusion
All young children <3 years of age at the time of diagnosis will receive MGTA-456 on the day of transplantation after a non-TBI containing myeloablative conditioning as TBI may have a damaging effect on brain development in the very young child. All patients aged 0-3 years will be conditioned with busulfan (BU), FLU and melphalan (MEL) as well as Tac/MMF immunoprophylaxis and G-CSF
干预措施: MGTA 456 Infusion (Drug)
FLU, CY, TBI + MGTA-456 infusion
All patients will receive MGTA-456 on the day of transplantation after myeloablative conditioning.
All patients aged 3-55 years will be conditioned with cyclophosphamide (CY) 120 mg/kg total dose, fludarabine (FLU) 75 m/m2 total dose and total body irradiation (TBI) 1320 cGy total dose as well as tacrolimus (Tac) and mycophenolate mofetil (MMF) immunoprophylaxis and granulocyte-colony stimulating factor (G-CSF)
干预措施: Total Body Irradiation (TBI) (Drug)
BU,FLU, MEL + MGTA-456 infusion
All young children <3 years of age at the time of diagnosis will receive MGTA-456 on the day of transplantation after a non-TBI containing myeloablative conditioning as TBI may have a damaging effect on brain development in the very young child. All patients aged 0-3 years will be conditioned with busulfan (BU), FLU and melphalan (MEL) as well as Tac/MMF immunoprophylaxis and G-CSF
干预措施: Granulocyte Colony-Stimulating Factor (G-CSF) (Drug)
BU,FLU, MEL + MGTA-456 infusion
All young children <3 years of age at the time of diagnosis will receive MGTA-456 on the day of transplantation after a non-TBI containing myeloablative conditioning as TBI may have a damaging effect on brain development in the very young child. All patients aged 0-3 years will be conditioned with busulfan (BU), FLU and melphalan (MEL) as well as Tac/MMF immunoprophylaxis and G-CSF
干预措施: Busulfan (BU) (Drug)
BU,FLU, MEL + MGTA-456 infusion
All young children <3 years of age at the time of diagnosis will receive MGTA-456 on the day of transplantation after a non-TBI containing myeloablative conditioning as TBI may have a damaging effect on brain development in the very young child. All patients aged 0-3 years will be conditioned with busulfan (BU), FLU and melphalan (MEL) as well as Tac/MMF immunoprophylaxis and G-CSF
干预措施: Melphalan (Drug)
FLU, CY, TBI + MGTA-456 infusion
All patients will receive MGTA-456 on the day of transplantation after myeloablative conditioning.
All patients aged 3-55 years will be conditioned with cyclophosphamide (CY) 120 mg/kg total dose, fludarabine (FLU) 75 m/m2 total dose and total body irradiation (TBI) 1320 cGy total dose as well as tacrolimus (Tac) and mycophenolate mofetil (MMF) immunoprophylaxis and granulocyte-colony stimulating factor (G-CSF)
干预措施: Tacrolimus (Tac) (Drug)
FLU, CY, TBI + MGTA-456 infusion
All patients will receive MGTA-456 on the day of transplantation after myeloablative conditioning.
All patients aged 3-55 years will be conditioned with cyclophosphamide (CY) 120 mg/kg total dose, fludarabine (FLU) 75 m/m2 total dose and total body irradiation (TBI) 1320 cGy total dose as well as tacrolimus (Tac) and mycophenolate mofetil (MMF) immunoprophylaxis and granulocyte-colony stimulating factor (G-CSF)
干预措施: MGTA 456 Infusion (Drug)
BU,FLU, MEL + MGTA-456 infusion
All young children <3 years of age at the time of diagnosis will receive MGTA-456 on the day of transplantation after a non-TBI containing myeloablative conditioning as TBI may have a damaging effect on brain development in the very young child. All patients aged 0-3 years will be conditioned with busulfan (BU), FLU and melphalan (MEL) as well as Tac/MMF immunoprophylaxis and G-CSF
干预措施: Mycophenolate Mofetil (MMF) (Drug)
BU,FLU, MEL + MGTA-456 infusion
All young children <3 years of age at the time of diagnosis will receive MGTA-456 on the day of transplantation after a non-TBI containing myeloablative conditioning as TBI may have a damaging effect on brain development in the very young child. All patients aged 0-3 years will be conditioned with busulfan (BU), FLU and melphalan (MEL) as well as Tac/MMF immunoprophylaxis and G-CSF
干预措施: Fludarabine (FLU) (Drug)
FLU, CY, TBI + MGTA-456 infusion
All patients will receive MGTA-456 on the day of transplantation after myeloablative conditioning.
All patients aged 3-55 years will be conditioned with cyclophosphamide (CY) 120 mg/kg total dose, fludarabine (FLU) 75 m/m2 total dose and total body irradiation (TBI) 1320 cGy total dose as well as tacrolimus (Tac) and mycophenolate mofetil (MMF) immunoprophylaxis and granulocyte-colony stimulating factor (G-CSF)
干预措施: Mycophenolate Mofetil (MMF) (Drug)
FLU, CY, TBI + MGTA-456 infusion
All patients will receive MGTA-456 on the day of transplantation after myeloablative conditioning.
All patients aged 3-55 years will be conditioned with cyclophosphamide (CY) 120 mg/kg total dose, fludarabine (FLU) 75 m/m2 total dose and total body irradiation (TBI) 1320 cGy total dose as well as tacrolimus (Tac) and mycophenolate mofetil (MMF) immunoprophylaxis and granulocyte-colony stimulating factor (G-CSF)
干预措施: Cyclophosphamide (CY) (Drug)
FLU, CY, TBI + MGTA-456 infusion
All patients will receive MGTA-456 on the day of transplantation after myeloablative conditioning.
All patients aged 3-55 years will be conditioned with cyclophosphamide (CY) 120 mg/kg total dose, fludarabine (FLU) 75 m/m2 total dose and total body irradiation (TBI) 1320 cGy total dose as well as tacrolimus (Tac) and mycophenolate mofetil (MMF) immunoprophylaxis and granulocyte-colony stimulating factor (G-CSF)
干预措施: Fludarabine (FLU) (Drug)
结局指标
主要结局
Percentage of Participants With Neutrophil Recover
时间窗: Day 14
Percentage of participants with neutrophil recovery by day 14 after transplantation in recipients of MGTA-456.
次要结局
- Event-Free Survival (EFS)(2 Years)
- Number of Days Alive Without Hospitalization(Day 0 and Day 100)
- Secondary Graft Failure(2 Years)
- Platelet Recovery(Day 42)
- Treatment Related Mortality (TRM)(6 Months)
- Grades II-IV Acute GVHD(Day 100)
- Grades III-IV Acute GVHD(Day 100)
- Chronic GVHD(1 Year)
- Relapse(2 Years)
- Non-catheter Associated Bacterial Infections(Day 100)
- Overall Survival (OS)(2 Years)