A Phase 2 Study of Nivolumab and Brentuximab Vedotin Consolidation After Autologous Stem Cell Transplantation in Patients With High-Risk Classical Hodgkin Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 62
- 试验地点
- 11
- 主要终点
- Progression-free Survival at 18 Months
研究概览
简要总结
This phase II trial studies how well nivolumab and brentuximab vedotin work after stem cell transplant in treating patients with high-risk classical Hodgkin lymphoma that has come back (recurrent) or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as nivolumab and brentuximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
详细描述
PRIMARY OBJECTIVE:
I. Assess the efficacy of nivolumab plus brentuximab vedotin consolidation after autologous stem cell transplantation (ASCT) in participants with relapsed/refractory Hodgkin lymphoma (HL), as assessed by 18-month progression-free survival (PFS).
SECONDARY OBJECTIVES:
I. Estimate the overall survival (OS), the cumulative incidence of relapse/progression, the cumulative incidence of non-relapse mortality (TRM) in participants with relapsed/ refractory HL who receive nivolumab plus brentuximab vedotin consolidation after ASCT.
II. Estimate the overall response rate to nivolumab plus brentuximab vedotin therapy in participants with measurable disease after ASCT.
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
- •Documented informed consent
- •Agreement to allow the use of archival tissue from pre-ASCT tumor biopsies
- •If unavailable, exceptions may be granted with study principal investigator (PI) approval
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- •Histologically confirmed diagnosis of classical Hodgkin lymphoma (excluding nodular lymphocyte predominant Hodgkin lymphoma) according to the World Health Organization (WHO) classification, with hematopathology review at the participating institution
- •Have high-risk relapsed or refractory Hodgkin lymphoma (HL), defined as at least one of the following:
- •Primary refractory disease to front-line therapy
- •Relapse within 1 year of completing front-line therapy
- •Extranodal involvement at the time of pre-ASCT relapse
- •B symptoms at pre-ASCT relapse
- •More than one type of pre-ASCT salvage therapy required
- •Planning to receive or have received autologous stem cell transplantation (ACST) per institutional standards as part of standard of care
- •Pre-ASCT participants may consent but will not be eligible to begin treatment until after ASCT, and will have to fulfill all inclusion and
排除标准
- •before starting protocol
- •All participants must initiate day 1 of protocol therapy within 30-60 days post stem cell reinfusion; study PI can grant exception for a patient to start as late as 75 days post stem cell reinfusion with a reasonable justification for a delay (e.g. recovery from post -ASCT toxicity) and this will not be a protocol deviation, nor require an exception to be filled
- •Recovery from ASCT toxicity as defined as outpatient status, able to drink, eat normally, and do not need intravenous hydration prior to day 1 of therapy
- •Achieved at least stable disease to salvage treatment determined by positron emission tomography (PET)/computed tomography (CT) using 2014 Lugano Classification prior to ASCT
- •Brentuximab vedotin naive OR had at least stable disease by Lugano Classification to prior brentuximab vedotin treatment
- •Absolute neutrophil count (ANC) >= 1000/mm^3
- •Platelets >= 50,000/mm^3
- •Hemoglobin >= 8 g/dL
- •Total bilirubin =< 1.5 x upper limit of normal (ULN) or 3 x ULN for Gilbert's disease
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
- •Creatinine clearance >= 40 mL/min per 24 hour urine collection or the Cockcroft-Gault formula
- •Calculated per institutional standard
- •Forced expiratory volume in one second (FEV1) and carbon monoxide diffusion capacity (DLCO) (adjusted for hemoglobin [Hb]) >= 50% adjusted
- •Women of childbearing potential (WOCBP) only: Negative urine or serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG])
- •If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- •Woman of childbearing potential (WOCBP): use two effective methods of contraception (hormonal or barrier method) or be surgically sterile, or abstain from heterosexual activity for the course of the study through 7 months post last dose of nivolumab
- •WOCBP defined as not being surgically sterilized or have not been free from menses for > 1 year
- •Male: use two effective methods of contraception (barrier method) or abstain from heterosexual activity with the first dose of study therapy through 7 months post last dose of nivolumab
- •Exclusion Criteria:
- •Post-ASCT anti-lymphoma or investigational therapy; immediate post-ASCT consolidative radiation therapy is allowed as long as it occurs prior to initiation of study therapy; baseline imaging and pulmonary function tests (PFTs) must be performed after completion of radiation
- •Previous allogeneic transplant
- •Total carmustine (BCNU) dose of > 600 mg/m^2 with prior treatments including transplant conditioning regimen
- •Live vaccine within 30 days prior to day 1 of protocol therapy (e.g. measles, mumps, rubella, varicella, yellow fever, rabies, Bacillus Calmette-Guerin [BCG], oral polio vaccine, and oral typhoid)
- •Refractory to prior brentuximab vedotin (i.e. progression while on treatment)
- •Refractory to prior anti-PD-1/PD-L1 agent
- •History of prior >= grade 3 hypersensitivity to either brentuximab vedotin or nivolumab
- •History of another primary malignancy that has not been in remission for at least 3 years; exceptions include:
- •Basal cell carcinoma of the skin or
- •Squamous cell carcinoma of the skin that has undergone potentially curative therapy or
- •In situ cervical cancer
- •Known active central nervous system (CNS) involvement by lymphoma, including parenchymal and/or lymphomatous meningitis
- •History of progressive multifocal leukoencephalopathy (PML)
- •Grade >= 2 peripheral neuropathy at the present time
- •Prior diagnosis of inherited or acquired immunodeficiency
- •Condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration; exceptions are:
- •Inhaled or topical steroids and
- •Adrenal replacement doses > 10 mg daily prednisone equivalents in the absence of active autoimmune disease
- •Uncontrolled illness including ongoing or active infection
- •History of or active pneumonitis or interstitial lung disease:
- •For history of pneumonitis to be an exclusion, patient had to have required supplemental oxygen or corticosteroid treatment; radiographic changes alone are not an exclusion
- •An active, known or suspected autoimmune disease; the following are exceptions:
- •Hemolytic anemia associated with the lymphoma (history of or at the present time)
- •Type I diabetes mellitus
- •Residual hypothyroidism due to autoimmune condition only requiring hormone replacement
- •Psoriasis not requiring systemic treatment, or
- •Conditions not expected to recur in the absence of an external trigger
- •Active or known history (standard pre-ASCT assessments) of:
- •Hepatitis B or C infection
- •Human immunodeficiency virus (HIV)
- •Acquired immunodeficiency syndrome (AIDS)
- 另有 4 项未显示
研究组 & 干预措施
Treatment (brentuximab vedotin, nivolumab)
Beginning 30-60 days post-ASCT, patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Brentuximab Vedotin (Drug)
Treatment (brentuximab vedotin, nivolumab)
Beginning 30-60 days post-ASCT, patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (brentuximab vedotin, nivolumab)
Beginning 30-60 days post-ASCT, patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Nivolumab (Biological)
结局指标
主要结局
Progression-free Survival at 18 Months
时间窗: From the first dose of study treatment to the first observation of disease relapse/progression or death from any cause, whichever occurs first, assessed at 18 months.
Progression-free survival will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error. When there is no censoring in progression-free survival prior to 18 months after the first dose of study treatment, the observed 18-month progression-free survival will be compared to the baseline of 65% by one-sided exact test of binomial proportion. In case of censoring in progression-free survival prior to 18 months after the first dose of study treatment, the Kaplan-Meier estimate for 18-month progression-free survival along with the Greenwood standard error estimator will be used for the testing of null hypothesis at 65%. Hodgkin Lymphoma(HL) response/progression was evaluated using 2014 Lugano Classification \[Cheson, Journal of Clinical Oncology 2014 Sep 20;32(27):3059-68\].
次要结局
- Overall Survival at 18 Months(From the first dose of study treatment to death from any cause, assessed up to 18 months)