Modified DHAP Versus Standard DHAP in Relapsed/Refractory Diffused Large B-cell Lymphoma.

Официальное название

Comparison of Effectiveness and Toxicities of Modified DHAP Protocol With Standard DHAP Protocol in Patients With Relapsed/Refractory Diffused Large B-cell Lymphoma.

Обзор

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.

Подробное описание

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.

Primary endpoint: Overall response rate (ORR), defined as complete or partial response per RECIL 2017 criteria.

Secondary endpoints: Progression-free survival (PFS), toxicity incidence and severity graded by CTCAE, and quality of life (QoL) assessed using the EORTC QLQ-C30 questionnaire.

Patients will be followed for treatment response, adverse events, and QoL changes. Toxicities will be documented using CTCAE forms, with particular attention to hematological toxicities (anemia, neutropenia, thrombocytopenia) and non-hematological toxicities (renal dysfunction, hepatotoxicity, mucositis, neuropathy).

The study anticipates that the modified DHAP regimen will demonstrate comparable or superior efficacy with a reduced incidence of severe toxicities, shorter hospital stays, and improved patient satisfaction. If successful, this regimen could support the transition of DHAP into outpatient administration, optimizing healthcare resource utilization in Pakistan and improving access to therapy for patients with poor prognoses.

Вмешательства

• Препарат Cisplatin
  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.
• Препарат Cisplatin
  The standard DHAP regimen defined as follows: * Dexamethasone: 40 mg orally or intravenously, given daily on days 1-4 * Cisplatin: 100 mg/m² administered intravenously as a continuous infusion over 24 hours on day 1 * Cytarabine: 2 × 2 g/m² intravenously over 3 hours, given on day 2 (two doses, 12 hours apart) This cycle is repeated every 21 days for 2-4 cycles, depending on patient tolerance and response.

Первичные конечные точки

• Overall Response rate (ORR) [Срок оценки: From enrollment to the end of treatment at 12 weeks]

Вторичные конечные точки (7)

• Complete Response (CR) [Срок оценки: From enrollment to the end of treatment at 12 weeks]
• Partial Response (PR) [Срок оценки: From enrollment to the end of treatment at 12 weeks]
• Minor Response (MR) [Срок оценки: From enrollment to the end of treatment at 12 weeks]
• Stable Disease [Срок оценки: From enrollment to the end of treatment at 12 weeks]
• Progressive Disease [Срок оценки: From enrollment to the end of treatment at 12 weeks]
• Progression free Survival (PFS) [Срок оценки: From enrollment to the end of treatment at 12 weeks]
• Quality of Life (QoL) [Срок оценки: at the end of treatment at 12 weeks]

Критерии участия

Критерии включения

• 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)

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Пакистан · 1 центр

• Mayo Hospital — Lahore

Идентификаторы

NCT: NCT07739654 · KEMU-IRB-77-RC-2026

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗