A Phase 2/3 Randomized Trial Investigating Daratumumab on a Modified Augmented BFM (aBFM) Backbone in Newly Diagnosed T-Lymphoblastic Leukemia (T-ALL) and T-Lymphoblastic Lymphoma (T-LL)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 1,708
- 主要终点
- Event-free survival (EFS) in patients with newly diagnosed T-cell lymphoblastic leukemia (T-ALL)
研究概览
简要总结
This phase II/III trial tests the addition of daratumumab to chemotherapy for treating patients with newly-diagnosed T-ALL and T-LL. Daratumumab is in a class of medications called monoclonal antibodies. It binds to a protein called CD38, which is found on some types of immune cells and cancer cells. Daratumumab may block CD38 and help the immune system kill cancer cells. Chemotherapy drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy with daratumumab may kill more cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. To compare the event-free survival (EFS) from the end of induction (EOI) in patients with newly diagnosed T-ALL who are randomized to either receive a modified augmented Berlin-Frankfurt-Münster (aBFM) chemotherapy backbone or a modified aBFM backbone with the addition of daratumumab.
II. To compare the EFS from the EOI in patients with newly diagnosed T-LL who are randomized to a modified aBFM chemotherapy backbone with bortezomib or to a modified aBFM backbone with bortezomib and the addition of daratumumab.
SECONDARY OBJECTIVES:
I. To compare health-related quality of life (HRQoL) and therapy-related toxicity and tolerability between patients with T-ALL or T-LL randomized to a modified aBFM backbone or to a modified aBFM backbone with the addition of daratumumab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 365 Days 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients must be enrolled on APEC14B1 and consented to eligibility screening (part A) prior to treatment and enrolled on AALL
- •Patients must be > 365 days and < 21 years of age at the time of diagnosis.
- •* Newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL) or T-lineage lymphoblastic lymphoma (T-LL) stages II-IV.
- •Note: A diagnosis of T-ALL is established when leukemic blasts lack myeloperoxidase or evidence of B-lineage derivation (CD19/CD22/CD20), and express either surface or cytoplasmic CD3 or two or more of the antigens CD8, CD7, CD5, CD4, CD2 or CD1a, and are present either in peripheral blood or > 25% in the bone marrow. If surface CD3 is expressed on all leukemic cells, additional markers of immaturity, including TdT, CD34 or CD99 will be assessed for expression. Cases with uncertain expression will receive additional review within the appropriate Children's Oncology Group (COG) reference laboratory.
- •For T-LL patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to T-ALL. For tissue processed by other means (i.e. paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of T-LL defined by the submitting institution will be accepted.
排除标准
- •Diagnosis of Down syndrome (trisomy 21).
- •Patients with known Charcot-Marie-Tooth disease.
- •* Patients must not have received any cytotoxic chemotherapy for either the current diagnosis of T-ALL, T-LL or for any cancer diagnosis prior to the initiation of protocol therapy on AALL2331 with the exception of:
- •Steroid pretreatment: Prednisone or methylprednisolone for ≤ 120 hours (5 days) in the 7 days prior to initiating induction chemotherapy or for ≤ 336 hours (14 days) in the 28 days prior to initiation of protocol therapy does not affect eligibility.
- •Intrathecal cytarabine; or
- •Pretreatment with hydroxyurea; or
- •600 cGy of chest irradiation, if medically necessary.
- •Pre-treatment with dexamethasone in the 28 days prior to initiation of protocol therapy is not allowed with the exception of a single dose of dexamethasone used during sedation to prevent or treat airway edema. Patients who receive a single dose of dexamethasone to prevent or treat airway edema in the 28 days preceding diagnosis are eligible for this study.
- •* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
- •Lactating females who plan to breastfeed their infants.
- •Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation.
- •Known severe persistent asthma anytime in the previous two years or uncontrolled asthma of any classification.
- •Peripheral neurotoxicity: Pre-existing ≥ grade 2 sensory or motor peripheral neurotoxicity.
- •Seizure disorder: Patients must not have an uncontrolled seizure disorder. Patients with a seizure history or a controlled seizure disorder are eligible. A controlled seizure disorder is defined as having stable or decreasing symptoms over the past 3 months without anti-epileptic medications or is on a stable or decreasing dose of anti-epileptic medication.
- •* Patients who are previously known to be seropositive for HIV except for HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of enrollment on this trial.
- •Patients with evidence of chronic hepatitis B (HBV) infection, except for patients who have an HBV viral load that is undetectable on suppressive therapy.
- •Patients with a history of hepatitis C virus (HCV) infection, except for those patients who have been treated and cured, or patients who are currently on HCV treatment who have an undetectable HCV viral load.
- •Patients with significant hepatic dysfunction defined as those with an alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) > 10x upper limit of normal (ULN) or direct bilirubin > 2x ULN unless the patient has known Gilbert's syndrome or has hepatic involvement from leukemic or lymphomatous infiltration.
- •All patients and/or their parents or legal guardians must sign a written informed consent.
- •All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.
研究组 & 干预措施
Group I, Arm A (T-ALL, no daratumumab)
See Detailed Description
干预措施: Radiation Therapy (Radiation)
Group II, Arm C (T-LL, no daratumumab)
See Detailed Description
干预措施: Positron Emission Tomography (Procedure)
Group II, Arm C (T-LL, no daratumumab)
See Detailed Description
干预措施: Questionnaire Administration (Other)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Biospecimen Collection (Procedure)
Group II, Arm C (T-LL, no daratumumab)
See Detailed Description
干预措施: Biopsy Procedure (Procedure)
Group II, Arm C (T-LL, no daratumumab)
See Detailed Description
干预措施: Biospecimen Collection (Procedure)
Group II, Arm C (T-LL, no daratumumab)
See Detailed Description
干预措施: Ultrasound Imaging (Procedure)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Biopsy Procedure (Procedure)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Bone Marrow Aspiration (Procedure)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Bone Marrow Biopsy (Procedure)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Questionnaire Administration (Other)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Radiation Therapy (Radiation)
Group I, Arm B (T-ALL, daratumumab)
See Detailed Description
干预措施: Thioguanine (Drug)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Prednisone (Drug)
Group I, Arm A (T-ALL, no daratumumab)
See Detailed Description
干预措施: Thioguanine (Drug)
Group II, Arm C (T-LL, no daratumumab)
See Detailed Description
干预措施: Calaspargase Pegol (Drug)
Group I, Arm B (T-ALL, daratumumab)
See Detailed Description
干预措施: Echocardiography Test (Procedure)
Group I, Arm B (T-ALL, daratumumab)
See Detailed Description
干预措施: Ultrasound Imaging (Procedure)
Group II, Arm C (T-LL, no daratumumab)
See Detailed Description
干预措施: Bone Marrow Aspiration (Procedure)
Group II, Arm C (T-LL, no daratumumab)
See Detailed Description
干预措施: Bone Marrow Biopsy (Procedure)
Group II, Arm C (T-LL, no daratumumab)
See Detailed Description
干预措施: Bone Scan (Procedure)
Group II, Arm C (T-LL, no daratumumab)
See Detailed Description
干预措施: Computed Tomography (Procedure)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Bone Scan (Procedure)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Ultrasound Imaging (Procedure)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Prednisolone (Drug)
Group II, Arm C (T-LL, no daratumumab)
See Detailed Description
干预措施: Vincristine Sulfate (Drug)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Calaspargase Pegol (Drug)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Therapeutic Hydrocortisone (Drug)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Thioguanine (Drug)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Vincristine Sulfate (Drug)
Group I, Arm B (T-ALL, daratumumab)
See Detailed Description
干预措施: Daunorubicin Hydrochloride (Drug)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Mercaptopurine Oral Suspension (Drug)
Group I, Arm B (T-ALL, daratumumab)
See Detailed Description
干预措施: Cytarabine (Drug)
Group I, Arm B (T-ALL, daratumumab)
See Detailed Description
干预措施: Dexamethasone (Drug)
Group I, Arm B (T-ALL, daratumumab)
See Detailed Description
干预措施: Doxorubicin Hydrochloride (Drug)
Group I, Arm B (T-ALL, daratumumab)
See Detailed Description
干预措施: Nelarabine (Drug)
Group I, Arm B (T-ALL, daratumumab)
See Detailed Description
干预措施: Pegaspargase (Drug)
Group I, Arm B (T-ALL, daratumumab)
See Detailed Description
干预措施: Vincristine Sulfate (Drug)
Group II, Arm C (T-LL, no daratumumab)
See Detailed Description
干预措施: Bortezomib (Drug)
Group II, Arm C (T-LL, no daratumumab)
See Detailed Description
干预措施: Cyclophosphamide (Drug)
Group II, Arm C (T-LL, no daratumumab)
See Detailed Description
干预措施: Prednisolone (Drug)
Group II, Arm C (T-LL, no daratumumab)
See Detailed Description
干预措施: Prednisone (Drug)
Group II, Arm C (T-LL, no daratumumab)
See Detailed Description
干预措施: Therapeutic Hydrocortisone (Drug)
Group II, Arm C (T-LL, no daratumumab)
See Detailed Description
干预措施: Thioguanine (Drug)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Bortezomib (Drug)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Cyclophosphamide (Drug)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Cytarabine (Drug)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Daratumumab (Biological)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Daunorubicin Hydrochloride (Drug)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Dexamethasone (Drug)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Methylprednisolone (Drug)
Group I, Arm A (T-ALL, no daratumumab)
See Detailed Description
干预措施: Calaspargase Pegol (Drug)
Group I, Arm A (T-ALL, no daratumumab)
See Detailed Description
干预措施: Cyclophosphamide (Drug)
Group I, Arm A (T-ALL, no daratumumab)
See Detailed Description
干预措施: Cytarabine (Drug)
Group I, Arm A (T-ALL, no daratumumab)
See Detailed Description
干预措施: Prednisone (Drug)
Group I, Arm A (T-ALL, no daratumumab)
See Detailed Description
干预措施: Therapeutic Hydrocortisone (Drug)
Group I, Arm A (T-ALL, no daratumumab)
See Detailed Description
干预措施: Lumbar Puncture (Procedure)
Group I, Arm A (T-ALL, no daratumumab)
See Detailed Description
干预措施: Biospecimen Collection (Procedure)
Group I, Arm B (T-ALL, daratumumab)
See Detailed Description
干预措施: Questionnaire Administration (Other)
Group I, Arm A (T-ALL, no daratumumab)
See Detailed Description
干预措施: Daunorubicin Hydrochloride (Drug)
Group I, Arm A (T-ALL, no daratumumab)
See Detailed Description
干预措施: Mercaptopurine Oral Suspension (Drug)
Group I, Arm A (T-ALL, no daratumumab)
See Detailed Description
干预措施: Methotrexate (Drug)
Group I, Arm A (T-ALL, no daratumumab)
See Detailed Description
干预措施: Prednisolone (Drug)
Group I, Arm A (T-ALL, no daratumumab)
See Detailed Description
干预措施: Methylprednisolone (Drug)
Group I, Arm A (T-ALL, no daratumumab)
See Detailed Description
干预措施: Pegaspargase (Drug)
Group I, Arm A (T-ALL, no daratumumab)
See Detailed Description
干预措施: Ultrasound Imaging (Procedure)
Group I, Arm B (T-ALL, daratumumab)
See Detailed Description
干预措施: Bone Marrow Aspiration (Procedure)
Group I, Arm B (T-ALL, daratumumab)
See Detailed Description
干预措施: Bone Marrow Biopsy (Procedure)
Group II, Arm C (T-LL, no daratumumab)
See Detailed Description
干预措施: Echocardiography Test (Procedure)
Group I, Arm B (T-ALL, daratumumab)
See Detailed Description
干预措施: Magnetic Resonance Imaging (Procedure)
Group I, Arm B (T-ALL, daratumumab)
See Detailed Description
干预措施: Methotrexate (Drug)
Group I, Arm B (T-ALL, daratumumab)
See Detailed Description
干预措施: Methylprednisolone (Drug)
Group I, Arm B (T-ALL, daratumumab)
See Detailed Description
干预措施: Prednisolone (Drug)
Group I, Arm B (T-ALL, daratumumab)
See Detailed Description
干预措施: Mercaptopurine Oral Suspension (Drug)
Group I, Arm B (T-ALL, daratumumab)
See Detailed Description
干预措施: Radiation Therapy (Radiation)
Group II, Arm C (T-LL, no daratumumab)
See Detailed Description
干预措施: Lumbar Puncture (Procedure)
Group II, Arm C (T-LL, no daratumumab)
See Detailed Description
干预措施: Pegaspargase (Drug)
Group II, Arm C (T-LL, no daratumumab)
See Detailed Description
干预措施: Methylprednisolone (Drug)
Group II, Arm C (T-LL, no daratumumab)
See Detailed Description
干预措施: Mercaptopurine Oral Suspension (Drug)
Group II, Arm C (T-LL, no daratumumab)
See Detailed Description
干预措施: Methotrexate (Drug)
Group II, Arm C (T-LL, no daratumumab)
See Detailed Description
干预措施: Radiation Therapy (Radiation)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Computed Tomography (Procedure)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Echocardiography Test (Procedure)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Lumbar Puncture (Procedure)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Positron Emission Tomography (Procedure)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Magnetic Resonance Imaging (Procedure)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Pegaspargase (Drug)
Group I, Arm A (T-ALL, no daratumumab)
See Detailed Description
干预措施: Questionnaire Administration (Other)
Group I, Arm B (T-ALL, daratumumab)
See Detailed Description
干预措施: Biospecimen Collection (Procedure)
Group I, Arm A (T-ALL, no daratumumab)
See Detailed Description
干预措施: Dexamethasone (Drug)
Group I, Arm A (T-ALL, no daratumumab)
See Detailed Description
干预措施: Doxorubicin Hydrochloride (Drug)
Group I, Arm A (T-ALL, no daratumumab)
See Detailed Description
干预措施: Echocardiography Test (Procedure)
Group I, Arm A (T-ALL, no daratumumab)
See Detailed Description
干预措施: Magnetic Resonance Imaging (Procedure)
Group I, Arm A (T-ALL, no daratumumab)
See Detailed Description
干预措施: Nelarabine (Drug)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Doxorubicin Hydrochloride (Drug)
Group II, Arm D (T-LL, daratumumab)
See Detailed Description
干预措施: Methotrexate (Drug)
Group I, Arm A (T-ALL, no daratumumab)
See Detailed Description
干预措施: Biopsy Procedure (Procedure)
Group I, Arm B (T-ALL, daratumumab)
See Detailed Description
干预措施: Daratumumab (Biological)
Group I, Arm B (T-ALL, daratumumab)
See Detailed Description
干预措施: Lumbar Puncture (Procedure)
Group II, Arm C (T-LL, no daratumumab)
See Detailed Description
干预措施: Magnetic Resonance Imaging (Procedure)
Group I, Arm B (T-ALL, daratumumab)
See Detailed Description
干预措施: Prednisone (Drug)
Group I, Arm B (T-ALL, daratumumab)
See Detailed Description
干预措施: Therapeutic Hydrocortisone (Drug)
Group II, Arm C (T-LL, no daratumumab)
See Detailed Description
干预措施: Cytarabine (Drug)
Group II, Arm C (T-LL, no daratumumab)
See Detailed Description
干预措施: Daunorubicin Hydrochloride (Drug)
Group II, Arm C (T-LL, no daratumumab)
See Detailed Description
干预措施: Dexamethasone (Drug)
Group I, Arm A (T-ALL, no daratumumab)
See Detailed Description
干预措施: Vincristine Sulfate (Drug)
Group I, Arm B (T-ALL, daratumumab)
See Detailed Description
干预措施: Calaspargase Pegol (Drug)
Group I, Arm B (T-ALL, daratumumab)
See Detailed Description
干预措施: Cyclophosphamide (Drug)
Group I, Arm A (T-ALL, no daratumumab)
See Detailed Description
干预措施: Bone Marrow Aspiration (Procedure)
Group I, Arm A (T-ALL, no daratumumab)
See Detailed Description
干预措施: Bone Marrow Biopsy (Procedure)
Group II, Arm C (T-LL, no daratumumab)
See Detailed Description
干预措施: Doxorubicin Hydrochloride (Drug)
Group I, Arm B (T-ALL, daratumumab)
See Detailed Description
干预措施: Biopsy Procedure (Procedure)
结局指标
主要结局
Event-free survival (EFS) in patients with newly diagnosed T-cell lymphoblastic leukemia (T-ALL)
时间窗: From date of randomization (randomization conducted at the end of induction [EOI]) to date of first event (consolidation failure, interim maintenance failure, relapse, secondary malignant neoplasm [SMN], death from any cause), assessed up to 4 years
Will compare EFS in patients with newly diagnosed T-ALL who are randomized to either receive a modified augmented Berlin-Frankfurt-Munich (aBFM) chemotherapy backbone or a modified aBFM backbone with the addition of daratumumab. Patients without an EFS event will be censored at the date of last follow-up. The survival time analyses assume a Weibull distribution with a shape parameter of 0.45 (based on historical controls). A phase 2/3 design will be used.
EFS in patients with newly diagnosed T-cell lymphoblastic lymphoma (T-LL)
时间窗: From date of randomization (randomization conducted at the EOI) to date of first event (consolidation failure, relapse, progressive disease, SMN, death from any cause), assessed up to 4 years
Will compare EFS in patients with newly diagnosed T-LL who are randomized to a modified aBFM chemotherapy backbone with bortezomib or to a modified aBFM backbone with bortezomib and the addition of daratumumab. Patients without an EFS event will be censored at the date of last follow-up. The survival time analyses assume a Weibull distribution with a shape parameter of 0.45 (based on historical controls).
次要结局
- Health-related quality of life (HRQoL)(Baseline (at time of randomization) to day 64 of consolidation)
- Incidence of therapy-related toxicity and tolerability(Assessed up to 3 cycles post randomization (each cycle is approximately 2-3 months))
- Overall survival (OS) in patients with newly diagnosed T-ALL(From date of randomization (randomization conducted at the EOI) to date of death (death due to any cause), assessed up to 4 years)
- Overall survival (OS) in patients with newly diagnosed T-LL(From date of randomization (randomization conducted at the EOI) to date of death (death due to any cause), assessed up to 4 years)