Brentuximab Vedotin With Cyclophosphamide, Doxorubicin, Etoposide, and Prednisone (BV-CHEP) for the Treatment of Adult T-Cell Leukemia/Lymphoma: A Pilot Study of the Rare Lymphoma Working Group
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 4
- 主要终点
- Complete Response Rate After 2-6 Cycles of Brentuximab Vedotin in Combination With Cyclophosphamide, Doxorubicin, Etoposide, and Prednisone (BV-CHEP)
研究概览
简要总结
Adult T-cell leukemia/lymphoma (ATLL) is a rare form of cancer found mostly among people from the Caribbean islands, Western Africa, Brazil, Iran, and Japan. Most cases of this disease in the United States occur along the East Coast due to emigration from the Caribbean islands. There is currently no standard treatment for ATLL. Research shows that patients who go into first time remission (respond completely or partially to treatment) and have a bone marrow transplant have the best outcomes. Traditional chemotherapy treatments have generally not worked well in patients with ATLL. Additionally, not all patients will be eligible for a bone marrow transplant.
The purpose of this study is to see how well individuals with ATLL respond to an investigational cancer treatment. This investigational treatment combines a drug called brentuximab vedotin with a standard chemotherapy treatment made up of cyclophosphamide, doxorubicin, etoposide, and prednisone. This treatment is considered investigational because it is not approved by the United States Food and Drug Administration (FDA) for the treatment of ATLL.
Brentuximab vedotin, also known as Adcetris, is approved by the United States Food and Drug Administration (FDA) for treatment of certain types of lymphomas, including peripheral T-cell lymphomas when combined with cyclophosphamide, doxorubicin, and prednisone in patients whose cancer cells express a type of marker called CD30.
Brentuximab vedotin is an antibody that also has a chemotherapy drug attached to it. Antibodies are proteins that are part of the immune system. They can stick to and attack specific targets on cancer cells. The antibody part of brentuximab vedotin sticks to a target called cluster of differentiation 30 (CD30) that is located on the outside of the cancer cells. Normal cells have little or no CD30 on their surface. ATLL cancer cells often have a larger amount of CD30 on their surface than normal cells. However, CD30 is found in different amounts on ATLL cancer cells. This study will also test the amount of CD30 found on each participant's cancer cells. Researchers will be looking to see if the response to the study treatment varies based on the amount of CD30 found on the outside participants' cancer cells.
In another study, brentuximab vedotin was combined in another study with cyclophosphamide, doxorubicin, and prednisone. The study included patients with various types of T-cell lymphomas. Two of the patients enrolled in that study had ATLL. Both had a complete response (no evidence of disease). The researchers in this study (LCCC 1637) have added etoposide to the combination of brentuximab vedotin with cyclophosphamide, doxorubicin, and prednisone. They predict that the addition of etoposide will improve patient outcomes. Research shows that etoposide helps improve outcomes in patients with certain types of T-cell lymphomas who undergo chemotherapy treatment. This investigational combination of brentuximab vedotin with cyclophosphamide, doxorubicin, etoposide, and prednisone is called BV-CHEP.
详细描述
STUDY OBJECTIVES
Primary Objective To define the proportion of subjects with CR after 4-6 cycles of brentuximab vedotin in combination with cyclophosphamide, doxorubicin, etoposide, and prednisone (BV-CHEP) in the treatment of adult T-cell leukemia/lymphoma.
Secondary Objectives
To estimate the overall response rate (ORR) with 4-6 cycles of BV-CHEP therapy in patients with adult T-cell leukemia/lymphoma.
To determine progression-free survival (PFS) for BV-CHEP in patients with adult T-cell leukemia/lymphoma who received or did not receive BV maintenance.
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
- •Subjects must meet all of the following inclusion criteria to participate in this study:
- •1. Informed consent and HIPAA authorization for release of personal health information obtained.
- •2. Age ≥ 18 years at the time of consent.
- •3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
- •4. Histological confirmation of biopsy-proven peripheral T-cell leukemia/lymphoma consistent with ATLL
- •* Included subtypes will be: acute, lymphomatous, and chronic unfavorable. Chronic unfavorable is defined as the chronic variant with at least one of the following: lactate dehydrogenase (LDH)\>upper limit of normal (ULN), blood urea nitrogen (BUN)\>ULN, Albumin\ 2.0 x institutional ULN
- •System: Hepatic - Bilirubin
- •Laboratory Value: ≤ 3.0 mg/dL
- •System: Hepatic - Aspartate aminotransferase (AST)
- •Laboratory Value: ≤ 2.5 × ULN
- •System: Hepatic - Alanine aminotransferase (ALT)
- •Laboratory Value: ≤ 2.5 × ULN
- •8. Females of childbearing potential must have a negative serum pregnancy test within three days (72 hours) prior to initiating study treatment. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months.
- •9. Females of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 24 weeks (6 months) after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method or an intrauterine device that meets \<1% failure rate for protection from pregnancy in the product label.
- •10. Male patients with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) starting with the first dose of study therapy through 24 weeks (6 months) after the last dose of study therapy.
- •11. As determined by the enrolling physician or protocol designee, willingness and ability of the subject to understand and comply with study procedures
- •12. Prior Treatment: Previously untreated or has received a maximum of one cycle of any combination chemotherapy (e.g. cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP), CHOEP, DA-EPOCH, doxorubicin, cyclophosphamide, cytarabine, vincristine, methotrexate/Etoposide, ifosfamide, cytarabine, methotrexate (CODOX-M/IVAC), HyperCVAD) within 4 weeks of signing the main consent form. Additionally, a patient may have taken antiretroviral therapy (e.g. azidothymidine (AZT) and/or IFN) at any time prior to study enrollment
- •13. CD30 expression determined by flow cytometry or IHC. NOTE: If CD30 testing was previously done on the biopsy sample from diagnosis, this information will be collected. If CD30 testing was not done, an archival sample from the biopsy used for diagnosis will be requested and tested for CD30. CD30 testing will also be done on the bone marrow tissue collected from the bone marrow exam. If we are unable to obtain an archival sample or if the bone marrow exam is negative, a new biopsy will be performed to confirm the diagnosis and test for CD30.
排除标准
- •Subjects who meet any of the following criteria should be excluded from study participation:
- •Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
- •Has a known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least five years.
- •Previous exposure to brentuximab vedotin (BV).
- •History of allergic response to BV-CHEP or its components or to any of the required prophylactic medications or reasonable alternatives.
- •Symptomatic cardiac disease including ventricular dysfunction, left ventricular ejection fraction < 40%, symptomatic coronary artery disease or symptomatic arrhythmias
- •Subjects with severe hepatic insufficiency Child-Pugh Score > 6
- •Subjects with severe renal impairment (i.e., creatinine clearance ≤ 30 mL/min; see Appendix B - Renal Impairment Guidelines).
- •Exclude patients with pre-existing neuropathy grade 2 or higher.
- •Patients receiving prohibited medications listed in the patient handout provided in 11.4 Appendix D: Prohibited Medications or Those to be used with Caution (ie, ketoconazole, itraconazole, ritonavir, macrolide antibiotics, erythromycin phenytoin, phenobarbital, carbamazepine, and valproic acid).
- •Patients with a parenchymal brain lesion thought to be consistent with active lymphoma on screening CT/MRI. Of note, patients with cerebrospinal fluid (CSF) involvement alone are not excluded.
研究组 & 干预措施
Open-label, Multicenter, Single-Arm
This is a single-arm intervention where patients will receive concurrent therapy with BV+CHEP [(brentuximab vedotin; 1.8 mg/kg IV, on D1 every 21 days) (cyclophosphamide 750 mg/m^2 on D1; doxorubicin 50 mg/m^2 on D1, etoposide 100 mg/m^2 IV infusion on D1-3; prednisone 100 mg orally once daily on D1-5; cycle length every 21 days)] for 2 to 6 cycles of induction therapy. After 6 cycles of BV + CHEP, responders (CR, PR or SD) who are not eligible for BMT and have CD30-positive ATLL will continue maintenance therapy with BV alone (1.8 mg/kg IV, every 21 days) until disease progression, withdrawal due to toxicity or death.
干预措施: CHEP (Drug)
Open-label, Multicenter, Single-Arm
This is a single-arm intervention where patients will receive concurrent therapy with BV+CHEP [(brentuximab vedotin; 1.8 mg/kg IV, on D1 every 21 days) (cyclophosphamide 750 mg/m^2 on D1; doxorubicin 50 mg/m^2 on D1, etoposide 100 mg/m^2 IV infusion on D1-3; prednisone 100 mg orally once daily on D1-5; cycle length every 21 days)] for 2 to 6 cycles of induction therapy. After 6 cycles of BV + CHEP, responders (CR, PR or SD) who are not eligible for BMT and have CD30-positive ATLL will continue maintenance therapy with BV alone (1.8 mg/kg IV, every 21 days) until disease progression, withdrawal due to toxicity or death.
干预措施: Brentuximab Vedotin (Drug)
结局指标
主要结局
Complete Response Rate After 2-6 Cycles of Brentuximab Vedotin in Combination With Cyclophosphamide, Doxorubicin, Etoposide, and Prednisone (BV-CHEP)
时间窗: 18 weeks
The response was assessed based on the International Workshop to standardize response criteria for malignant lymphomas (i.e., Lugano Criteria per Cheson, et al. J Clin Oncol. 2014;32(27):3059-68; Complete Response: Positron emission tomography (PET): Complete metabolic response Computerized tomography (CT): Target must regress to ≤ 1.5 cm in the largest transverse diameter (LDi) or no extra lymphatic sites of disease. Partial Response: PET: reduced uptake compared with baseline, and CT: ≥50% decrease in the sum of the products of diameters (SPD).No Response or Stable Disease: No metabolic response on PET or \< 50% decrease from baseline in SPD of up to 6 dominant, measurable nodes and extra nodal sites on CT. Progressive Disease: PET: Score 4 or 5 with an increase in the intensity of uptake or CT: an individual node/lesion must be abnormal with LDi \> 1.5 cm, increase by ≥ 50% from the cross product of the LDi and shortest axis perpendicular to LDi (SDi).
次要结局
- Overall Response Rate (ORR) Associated With 2-6 Cycles of BV-CHEP Therapy in Patients With Adult T-Cell Leukemia/Lymphoma.(Up to 24 months)
- Progression-free Survival (PFS) for BV-CHEP in Patients With Adult T-cell Leukemia/Lymphoma(Up to 15.2 months)
- Duration of Response to BV-CHEP in Patients With Adult T-cell Leukemia/Lymphoma(Up to 24 months)
- Overall Survival (OS) of Patients With Adult T-cell Leukemia/Lymphoma Treated With BV-CHEP Who Received or Did Not Receive BV Maintenance Therapy.(Up to 68 months)
- BV-CHEP and BV Maintenance Therapy-Attributed Grade ≥3 Adverse Events Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4)(Up to 24 months)
- Progression-free Survival (PFS) for BV Maintenance(Up to Day 309)