Comparison of Effectiveness and Toxicities of Modified DHAP Protocol With Standard DHAP Protocol in Patients With Relapsed/Refractory Diffused Large B-cell Lymphoma.
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 74
- 试验地点
- 1
- 主要终点
- Overall Response rate (ORR)
研究概览
简要总结
This Phase III randomized controlled trial evaluates the effectiveness and toxicity profile of a modified DHAP regimen compared to the standard DHAP regimen in adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). The DHAP regimen (cisplatin, cytarabine, dexamethasone) is widely used as salvage therapy but is associated with significant toxicities, including renal dysfunction and severe myelosuppression. The modified DHAP protocol fractionates cisplatin and cytarabine administration to reduce nephrotoxicity, improve tolerability, and potentially allow outpatient treatment.
A total of 74 patients will be randomized (37 per arm) to receive either the modified or standard DHAP regimen. The primary endpoint is overall response rate (ORR) assessed by RECIL 2017 criteria. Secondary endpoints include progression-free survival (PFS), toxicity incidence and severity graded by CTCAE, and quality of life measured by EORTC QLQ-C30.
The study anticipates that the modified DHAP regimen will demonstrate comparable or superior efficacy with reduced severe toxicities, shorter hospital stays, and improved patient satisfaction. Findings may support transitioning DHAP into outpatient administration, optimizing healthcare resource utilization in Pakistan.
详细描述
This study is a randomized controlled trial designed to compare the effectiveness and toxicity profile of a modified DHAP regimen versus the standard DHAP regimen in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
DLBCL is the most common subtype of non-Hodgkin lymphoma, with a significant proportion of patients experiencing relapse or refractory disease after initial therapy. The standard DHAP regimen (cisplatin, cytarabine, dexamethasone) has been widely used as salvage therapy, achieving response rates of up to 70%. However, its use is limited by severe toxicities, including renal dysfunction, infections, and profound myelosuppression.
The modified DHAP regimen alters the administration schedule of cisplatin and cytarabine. Cisplatin is fractionated into smaller doses over multiple days rather than a single 24-hour continuous infusion, and cytarabine is administered over two consecutive days. This modification is hypothesized to reduce nephrotoxicity, improve tolerability, and allow outpatient administration, while maintaining or enhancing cytotoxic synergy between cisplatin and cytarabine.
A total of 74 patients will be enrolled and randomized into two arms (37 per arm):
- Arm A (Modified DHAP): Dexamethasone 40 mg PO/IV days 1-4; Cisplatin 50 mg/m² over 6 hours days 1-2; Cytarabine 2 g/m² IV over 3 hours days 1-2.
- Arm B (Standard DHAP): Dexamethasone 40 mg PO/IV days 1-4; Cisplatin 100 mg/m² continuous infusion over 24 hours day 1; Cytarabine 2×2 g/m² IV over 3 hours day 2.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed relapsed or refractory DLBCL
- •Adults ≥ 18 years
- •At least one prior line of therapy for lymphoma
- •ECOG performance status 0-2
- •Ability to provide informed consent and comply with study requirements
- •Adequate organ function:
- •Hematologic: ANC ≥ 1,000 cells/mm³, Platelets ≥ 75,000 cells/mm³
- •Renal: Serum creatinine ≤ 1.5 × ULN
- •Hepatic: Total bilirubin ≤ 1.5 × ULN, AST/ALT ≤ 2.5 × ULN (if no liver metastases)
排除标准
- •History of other malignancies within last 5 years (except non-melanoma skin cancer or localized prostate cancer)
- •Pregnant or breastfeeding women
- •Significant uncontrolled medical conditions (e.g., cardiovascular disease, uncontrolled diabetes)
- •Receipt of investigational agents within 30 days prior to enrollment
- •Known severe allergic reactions to DHAP components (dexamethasone, cytarabine, cisplatin)
- •Concurrent anti-cancer treatments (chemotherapy, radiotherapy) during study period
研究组 & 干预措施
standard DHAP
Dexamethasone 40 mg PO/IV days 1-4; Cisplatin 100 mg/m² continuous infusion over 24 hours day 1; Cytarabine 2×2 g/m² IV over 3 hours day 2.
干预措施: Cytarabine (Ara-C) (Drug)
standard DHAP
Dexamethasone 40 mg PO/IV days 1-4; Cisplatin 100 mg/m² continuous infusion over 24 hours day 1; Cytarabine 2×2 g/m² IV over 3 hours day 2.
干预措施: Cisplatin (Drug)
Modified DHAP
Dexamethasone 40 mg PO/IV days 1-4; Cisplatin 50 mg/m² over 6 hours days 1-2; Cytarabine 2 g/m² IV over 3 hours days 1-2.
干预措施: Cisplatin (modified schedule) (Drug)
Modified DHAP
Dexamethasone 40 mg PO/IV days 1-4; Cisplatin 50 mg/m² over 6 hours days 1-2; Cytarabine 2 g/m² IV over 3 hours days 1-2.
干预措施: Dexametasone (Drug)
Modified DHAP
Dexamethasone 40 mg PO/IV days 1-4; Cisplatin 50 mg/m² over 6 hours days 1-2; Cytarabine 2 g/m² IV over 3 hours days 1-2.
干预措施: Cytarabine (Ara-C) (Modified schedule) (Drug)
standard DHAP
Dexamethasone 40 mg PO/IV days 1-4; Cisplatin 100 mg/m² continuous infusion over 24 hours day 1; Cytarabine 2×2 g/m² IV over 3 hours day 2.
干预措施: Dexametasone (Drug)
结局指标
主要结局
Overall Response rate (ORR)
时间窗: From enrollment to the end of treatment at 12 weeks
The Overall Response Rate (ORR) is defined as the percentage of patients achieving either a Complete Response (CR) or a Partial Response (PR), assessed according to RECIL 2017 criteria. * Complete Response (CR): * Disappearance of all target lesions * Lymph nodes \<10 mm * Normalization of FDG-PET (Deauville 1-3) * No bone marrow involvement, no new lesions * Partial Response (PR): * ≥30% decrease in the sum of longest diameters of target lesions * FDG-PET positive (Deauville 4-5) * May still have bone marrow involvement * No new lesions
次要结局
- Complete Response (CR)(From enrollment to the end of treatment at 12 weeks)
- Partial Response (PR)(From enrollment to the end of treatment at 12 weeks)
- Minor Response (MR)(From enrollment to the end of treatment at 12 weeks)
- Stable Disease(From enrollment to the end of treatment at 12 weeks)
- Progressive Disease(From enrollment to the end of treatment at 12 weeks)
- Progression free Survival (PFS)(From enrollment to the end of treatment at 12 weeks)
- Quality of Life (QoL)(at the end of treatment at 12 weeks)
- Progression free Survival (PFS)(From enrollment to up to 2 years post-treatment)
- Adverse Events(From enrollment to the end of treatment at 12 weeks)
研究者
Abbas Khokhar
Professor of Medical Oncology and Radiotherapy
King Edward Medical University