Phase IIa Study of Addition of Itacitinib With Tacrolimus/Sirolimus Regimen for GVHD Prophylaxis in Fludarabine and Melphalan Non-Myeloablative Conditioning Hematopoietic Cell Transplantation for Acute Leukemias, MDS or MF
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 59
- 试验地点
- 1
- 主要终点
- Graft-versus-host Disease Free Relapse Free (GRFS) at 1 Year
研究概览
简要总结
This phase IIa trial studies the side effects of itacitinib when given together with standard treatment (tacrolimus and sirolimus), and to see how well it works in preventing graft-versus-host-disease (GVHD) in patients with acute leukemia, myelodysplastic syndrome or myelofibrosis who are undergoing reduced intensity conditioning donor stem cell transplantation. GVHD is a common complication after donor stem cell transplantation, resulting from donor immune cells recognizing recipients' cells and attacking them. Adding itacitinib to tacrolimus and sirolimus may reduce the risk GVHD and ultimately improve overall outcome and survival after donor stem cell transplantation.
详细描述
PRIMARY OBJECTIVE:
I. Following a patient safety lead-in, estimate graft-versus-host disease free relapse free (GRFS) survival at 1- year post allogeneic stem cell transplantation (alloHCT).
SECONDARY OBJECTIVES:
I. Estimate the cumulative incidence of acute graft-versus-host disease (aGVHD) and non-relapse mortality (NRM) at 100-days post-transplant.
II. Estimate the cumulative incidence of chronic GVHD at 1- and 2-years post-transplant.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented informed consent of the participant and/or legally authorized representative
- •Assent, when appropriate, will be obtained per institutional guidelines
- •Agreement to allow the use of archival tissue from diagnostic tumor biopsies
- •If unavailable, exceptions may be granted with study principal investigator (PI) approval
- •Performance status: Karnofsky >= 70%
- •Patients with neoplastic hematologic disorders with indication of allogeneic transplant according to the standard guidelines as follows:
- •Acute leukemia (AL) in first complete response (CR1) or subsequent complete response (CR) or active disease with bone marrow (BM) blast of < 5%
- •Myelodysplastic syndrome (MDS) with intermediate-2 or high risk per International Prognostic Scoring System (IPSS) or
- •Myelofibrosis; primary or secondary if intermediate-2 or high risk per Dynamic International Prognostic Scoring System (DIPPS)
- •All candidates for this study must have a matched related donor (MRD) who is willing to donate BM or peripheral blood stem cells or an 8/8 allele matched unrelated donor (MUD)
- •Total bilirubin =< 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease) (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated. In case of active disease, evaluation should be done within 15 days)
- •Aspartate aminotransferase (AST) =< 2.5 x ULN (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated. In case of active disease, evaluation should be done within 15 days)
- •Alanine aminotransferase (ALT) =< 2.5 x ULN (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated. In case of active disease, evaluation should be done within 15 days)
- •Creatinine clearance of >= 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated. In case of active disease, evaluation should be done within 15 days)
- •Left ventricular ejection fraction (LVEF) >= 50%
- •Note: To be performed within 28 days prior to day 1 of protocol therapy
- •If able to perform pulmonary function tests: forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide (DLCO) (diffusion capacity) >= 50% of predicted (corrected for hemoglobin). If unable to perform pulmonary function tests: oxygen (O2) saturation > 92% on room air.
- •Note To be performed within 28 days prior to day 1 of protocol therapy
- •Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab) combination (combo), hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma reagin measurement [RPR])
- •If HCV positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed
- •Meets other institutional and federal requirements for infectious disease titer requirements
- •Note Infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy
- •Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- •Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy
- •Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
排除标准
- •Chemotherapy, radiation therapy, biological therapy, and/or immunotherapy within 21 days prior to day 1 of protocol therapy
- •Note: Conditioning regimen within 21 days prior to day 1 of protocol therapy is not considered as an exclusion criterion
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
- •Psychological issues, no appropriate caregivers identified, or non-compliant to medication
- •Uncontrolled medical or psychiatric disorders which may preclude patients to undergo clinical studies (Discretion of the attending physician)
- •Active diarrhea due to inflammatory bowel disease or malabsorption syndrome
- •Clinically significant uncontrolled illness
- •Active, uncontrolled systemic infection (bacterial, viral, or fungal) requiring antibiotics
- •Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
- •Diagnosis of Gilbert's disease
- •Other active malignancy
- •Females only: Pregnant or breastfeeding
- •Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
- •Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
研究组 & 干预措施
Treatment (itacitinib adipate, tacrolimus, sirolimus)
RIC: Patients receive fludarabine via infusion on days -9 to -5 and melphalan on day -4 in the absence of disease progression or unacceptable toxicity.
ALLOGENEIC HSCT: Patients undergo HSCT on day 0.
GVHD PROPHYLAXIS: Patients receive itacitinib PO QD beginning on day -3 and continuing until day 100 in the absence of disease progression or unacceptable toxicity. Patients also receive tacrolimus IV or PO and sirolimus PO beginning day -3 and continuing until day 100 with a taper in the absence of disease progression or unacceptable toxicity.
干预措施: Fludarabine (Drug)
Treatment (itacitinib adipate, tacrolimus, sirolimus)
RIC: Patients receive fludarabine via infusion on days -9 to -5 and melphalan on day -4 in the absence of disease progression or unacceptable toxicity.
ALLOGENEIC HSCT: Patients undergo HSCT on day 0.
GVHD PROPHYLAXIS: Patients receive itacitinib PO QD beginning on day -3 and continuing until day 100 in the absence of disease progression or unacceptable toxicity. Patients also receive tacrolimus IV or PO and sirolimus PO beginning day -3 and continuing until day 100 with a taper in the absence of disease progression or unacceptable toxicity.
干预措施: Itacitinib Adipate (Drug)
Treatment (itacitinib adipate, tacrolimus, sirolimus)
RIC: Patients receive fludarabine via infusion on days -9 to -5 and melphalan on day -4 in the absence of disease progression or unacceptable toxicity.
ALLOGENEIC HSCT: Patients undergo HSCT on day 0.
GVHD PROPHYLAXIS: Patients receive itacitinib PO QD beginning on day -3 and continuing until day 100 in the absence of disease progression or unacceptable toxicity. Patients also receive tacrolimus IV or PO and sirolimus PO beginning day -3 and continuing until day 100 with a taper in the absence of disease progression or unacceptable toxicity.
干预措施: Melphalan (Drug)
Treatment (itacitinib adipate, tacrolimus, sirolimus)
RIC: Patients receive fludarabine via infusion on days -9 to -5 and melphalan on day -4 in the absence of disease progression or unacceptable toxicity.
ALLOGENEIC HSCT: Patients undergo HSCT on day 0.
GVHD PROPHYLAXIS: Patients receive itacitinib PO QD beginning on day -3 and continuing until day 100 in the absence of disease progression or unacceptable toxicity. Patients also receive tacrolimus IV or PO and sirolimus PO beginning day -3 and continuing until day 100 with a taper in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Other)
Treatment (itacitinib adipate, tacrolimus, sirolimus)
RIC: Patients receive fludarabine via infusion on days -9 to -5 and melphalan on day -4 in the absence of disease progression or unacceptable toxicity.
ALLOGENEIC HSCT: Patients undergo HSCT on day 0.
GVHD PROPHYLAXIS: Patients receive itacitinib PO QD beginning on day -3 and continuing until day 100 in the absence of disease progression or unacceptable toxicity. Patients also receive tacrolimus IV or PO and sirolimus PO beginning day -3 and continuing until day 100 with a taper in the absence of disease progression or unacceptable toxicity.
干预措施: Questionnaire Administration (Other)
Treatment (itacitinib adipate, tacrolimus, sirolimus)
RIC: Patients receive fludarabine via infusion on days -9 to -5 and melphalan on day -4 in the absence of disease progression or unacceptable toxicity.
ALLOGENEIC HSCT: Patients undergo HSCT on day 0.
GVHD PROPHYLAXIS: Patients receive itacitinib PO QD beginning on day -3 and continuing until day 100 in the absence of disease progression or unacceptable toxicity. Patients also receive tacrolimus IV or PO and sirolimus PO beginning day -3 and continuing until day 100 with a taper in the absence of disease progression or unacceptable toxicity.
干预措施: Sirolimus (Drug)
Treatment (itacitinib adipate, tacrolimus, sirolimus)
RIC: Patients receive fludarabine via infusion on days -9 to -5 and melphalan on day -4 in the absence of disease progression or unacceptable toxicity.
ALLOGENEIC HSCT: Patients undergo HSCT on day 0.
GVHD PROPHYLAXIS: Patients receive itacitinib PO QD beginning on day -3 and continuing until day 100 in the absence of disease progression or unacceptable toxicity. Patients also receive tacrolimus IV or PO and sirolimus PO beginning day -3 and continuing until day 100 with a taper in the absence of disease progression or unacceptable toxicity.
干预措施: Tacrolimus (Drug)
结局指标
主要结局
Graft-versus-host Disease Free Relapse Free (GRFS) at 1 Year
时间窗: From the date of transplantation to the first time of observing following events: grade 3-4 acute graft versus host disease (GVHD), chronic GVHD requiring systemic treatment, relapse, or death, whichever occurs first, assessed at 1 year post transplant.
GRFS is defined as time from the date of transplantation to the first time of observing following events: grade 3-4 acute graft versus host disease (GVHD), chronic GVHD requiring systemic treatment, relapse, or death, whichever occurs first. Kaplan-Meier curve will be generated for GRFS.
次要结局
- Cumulative Incidence of Grade II-IV Acute GVHD(From day 0 (date of stem cell infusion) through 100 days post-transplant)
- Progression Free Survival (PFS)(From the date of stem cell infusion to the date of death, disease relapse/progression, or last follow-up, whichever occurs first, assessed at 1 year post transplant)