A Phase II, Open Label, Multicenter Trial of Daratumumab in Combination With Gemcitabine, Dexamethasone and Cisplatin (D-GDP) in Patients With Relapsed/Refractory CD38 Positive Peripheral T-cell Lymphoma Not Otherwise Specified (PTCL-NOS), Angioimmunoblastic T-cell Lymphoma (AITL) and Other Nodal Lymphomas of TFH Cell Origin
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 8
- 试验地点
- 7
- 主要终点
- Complete Response Rate (CRR)
研究概览
简要总结
FIL_Dara-GDP is a phase II, open label, multicenter clinical trial. The sponsor of this clinical trial is Fondazione Italiana Linfomi (FIL). The primary objective is to evaluate the efficacy of 4 courses of D-GDP (Daratumumab in combination with Gemcitabine, Cisplatin, Dexamethasone) in terms of complete response in patients with peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL) and other nodal lymphomas of T follicular helper cells (TFH cells) origin refractory/relapsed after at least one and no more than two previous lines of therapy.
详细描述
This is an open-label, multicenter, single arm, single-stage phase II trial. After the patient signs the written informed consent the patient will enter the screening phase planning baseline assessments and a concomitant upfront confirmation of diagnosis of Peripheral T-Cell Lymphoma Not Otherwise Specified (PTCL-NOS), Angioimmunoblastic T-cell lymphoma (AITL) or Nodal Lymphoma of T Follicular Helper cells (TFH cells) origin and a central evaluation of immunohistochemical positivity of CD38 (cluster of differentiation 38) on bioptic material used to perform local diagnosis of relapsed disease, or that used for the more recent biopsy in the case of refractory patients. A core needle biopsy is considered sufficient for review and CD38 evaluation. Evaluation at central laboratory can be performed in bone marrow sections in those patients with only bone marrow lymphoma infiltration.
Only patients with confirmed eligible diagnosis and a percentage of CD38 positive tumor cells ≥ 5% will be considered eligible for study treatment.
The treatment consists of an induction phase and a maintenance phase.
Induction phase:
4-6 courses (according to response after cycle 4 and to patient compliance) of D-GDP (Daratumumab in combination with Gemcitabine, Cisplatin, Dexamethasone) every 21 days pursuant to the following schedule:
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically documented diagnosis of CD38 (cluster of differentiation 38) positive PTCL-NOS, AITL and other nodal lymphomas of TFH cell origin as defined in the 2017 edition of the World Health Organization (WHO) classification. Patients with only bone marrow involvement are eligible.
- •Note: Only patients with a centrally assessed percentage of CD38 positive tumor cells ≥ 5% in the relapse biopsy, or in the more recent biopsy in the case of refractory patients, will be considered eligible for protocol study treatment.
- •Age 18-70 years
- •Relapsed or refractory to one previous lines of treatment (autologous transplantation as a consolidation to the first line of therapy should not be considered a second line)
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) < 2
- •At least one site of measurable nodal disease at baseline ≥ 2.0 cm in the longest transverse diameter as determined by CT scan (MRI is allowed only if CT scan cannot be performed). Note: Patients with only bone marrow involvement are eligible
- •Adequate hematological counts defined as follows:
- •Absolute Neutrophil count (ANC) > 1.0 x 109/L unless due to bone marrow involvement by lymphoma
- •Platelet count > 100.000/mm3 unless due to bone marrow involvement by lymphoma
- •Adequate renal function defined as follows:
- •Creatinine clearance ≥ 40 mL/min (Cockcroft-Gault formula)
- •Adequate hepatic function per local laboratory reference range as follows:
- •Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x upper limit of normal (ULN)
- •Bilirubin ≤1.5 x upper limit of normal (ULN)(unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
- •Subject understands and voluntarily signs an informed consent form approved by an Independent Ethics Committee (IEC), prior to the initiation of any screening or study-specific procedures
- •Subject must be able to adhere to the study visit schedule and other protocol requirements
- •Life expectancy ≥ 3 months
- •Women must be:
- •postmenopausal for at least 1 year (must not have had a natural menses for at least 12 months)
- •surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy),
- •completely abstinent (periodic abstinence from intercourse is not permitted) or if sexually active, be practicing two highly effective methods of birth control (e.g., prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double barrier method (e.g.: condoms, diaphragm, or cervical cap, with spermicidal foam, cream, or gel, male partner sterilization) as local regulations permit, before entry, and must agree to continue to use the same method of contraception throughout the study. They must also be prepared to continue birth control measures for at least 3 months after terminating treatment.
- •Women of childbearing potential must have a negative pregnancy test at screening
- •Men must agree to use an acceptable method of contraception (for themselves or female partners as listed above) for the duration of the study. Men must agree to use a double barrier method of birth control and to not donate sperm during the study and for 3 months after receiving the last dose of study drug.
- •Male even if surgically sterilized (i.e., status post vasectomy) must agree to 1 of the following:
- •practice effective barrier contraception during the entire study treatment period and through 3 months after the last dose of study drug, or
- •agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post ovulation methods for the female partner] and withdrawal are not acceptable methods of contraception)
排除标准
- •Histological diagnosis different from CD38 positive PTCL-NOS, AITL, and other nodal lymphomas of TFH cell origin
- •More than two lines of previous treatment (autologous stem cell transplant performed as part of consolidation to a previous line of therapy should not be considered as a line of therapy)
- •Previous treatment with Gemcitabine or Platinum based regimens; patients who received a single course of Platinum based course (i.e. DHAP) are not excluded
- •Prior therapy with monoclonal antibody anti CD38 (against cluster of differentiation 38)
- •Concomitant experimental therapy
- •Relapse after allo SCT
- •Central nervous system (CNS) involvement with lymphoma
- •Subject has received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, investigational therapy, including targeted small molecule agents within 14 days prior to the first dose of study drug
- •Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) requiring treatment
- •Subject is:
- •Known to be seropositive for human immunodeficiency virus (HIV)
- •Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (i.e., subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-hepatitis B core antigen (HBc)] ± antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR
- •Known to be seropositive for hepatitis C (except in the setting of a Sustained Virologic Response(SVR), defined as aviremia at least 12 weeks after completion of antiviral therapy)
- •Cardiovascular disease (NYHA class ≥2)
- •Creatinine Clearance < 40 mL/min (Cockcroft-Gault formula)
- •Significant history of neurologic, psychiatric, endocrinological, metabolic, immunologic, or hepatic disease that would preclude participation in the study or compromise ability to give informed consent
- •Any history of other active malignancies within 3 years prior to study entry, with the exception of adequately treated in situ carcinoma of the cervix uterine, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin, previous malignancy confined and surgically resected with curative intent.
- •Uncontrolled and/or active systemic infection (viral, bacterial or fungal)
- •Evidence of any other clinically significant uncontrolled condition(s)
- •If female, the patient is pregnant or breast-feeding
研究组 & 干预措施
Daratumumab-GDP
This is an open-label, multicenter, single arm, single-stage phase II trial. After the patient signs the written informed consent the patient will enter the screening phase planning baseline assessments and a concomitant upfront confirmation of diagnosis of PTCL-NOS, AITL or nodal lymphoma of TFH cell origin and a central evaluation of immunohistochemical positivity of CD38 on bioptic material used to perform local diagnosis of relapsed disease, or that used for the more recent biopsy in the case of refractory patients. A core needle biopsy is considered sufficient for review and CD38 evaluation. Evaluation at central laboratory can be performed in bone marrow sections in those patients with only bone marrow lymphoma infiltration.
Only patients with confirmed eligible diagnosis and a percentage of CD38 positive tumor cells ≥ 5% will be considered eligible for study treatment.
The treatment consists of an induction phase and a maintenance phase.
干预措施: Daratumumab (Drug)
结局指标
主要结局
Complete Response Rate (CRR)
时间窗: the endpoint will be assessed from the start date of therapy to the end of the first four cycles of therapy (cycles of 21 days).
The Complete Response Rate is defined as the percentage of patient in Complete Remission (according to Lugano classification response Criteria). It will be assessed after the first 4 cycles of D-GDP chemotherapy. In case of early discontinuation, efficacy will be assessed at the End Of Treatment (EOT) visit. Patients without response assessment (due to whatever reason) will be considered as non-responders. CR: complete radiological response, no extralymphatic sites, no new lesions, organ enlargement regress to normal and normal morphology of bone marrow; PR: \>=50% decrease of sum of the product of perpendicular diameter of up to 6 dominant, measurable nodes and and extranodal sites.
次要结局
- Progression-Free Survival (PFS)(The endpoint will be assessed from the start date of therapy up to 3 months.)
- Toxicity - Frequency of Relevant Toxicities(the endpoint was assessed after 26 months from the date of starting therapy in place of the planned 42 months, due the early interruption of the study)
- Overall Survival (OS)(The end point will be assessed from the start date of therapy up to 3 months.)
- Overall Response Rate (ORR)(the endpoint will be assessed from the start date of therapy to the end of the first four cycles of therapy (cycles of 21 days) and at each restaging)