DLBCL - Diffuse Large B Cell Lymphoma
Conditions
Keywords
DLBCL, DHAP, B cell Lymphoma
Brief summary
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.
Detailed description
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.
Interventions
DRUGCisplatin (modified schedule)
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.
DRUGCisplatin
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.
DRUGDexametasone
The standard dexamethasone dosing regimen per RECIL 2017 criteria
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.
DRUGCytarabine (Ara-C) (Modified schedule)
The modified DHAP regimen alters the administration schedule of cisplatin and cytarabine. Cytarabine is administered over two consecutive days.
Sponsors
King Edward Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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)
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response rate (ORR) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response (CR) | From enrollment to the end of treatment at 12 weeks | * 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) | From enrollment to the end of treatment at 12 weeks | * 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 |
| Minor Response (MR) | From enrollment to the end of treatment at 12 weeks | * ≥10% decrease in the sum of longest diameters of target lesions, but not enough to qualify as PR (≥30%) * FDG-PET may still show uptake (any finding) * Bone marrow involvement may persist * No new lesions |
| Stable Disease | From enrollment to the end of treatment at 12 weeks | * \<10% decrease or ≤20% increase in the sum of longest diameters of target lesions * FDG-PET findings may remain positive * Bone marrow involvement may persist * No new lesions |
| Progressive Disease | From enrollment to the end of treatment at 12 weeks | * \>20% increase in the sum of longest diameters of target lesions * For small lymph nodes (\<15 mm post-therapy), a minimum absolute increase of 5 mm and long diameter \>15 mm is required * Appearance of new lesions automatically qualifies as PD * Any FDG-PET finding consistent with progression * Bone marrow involvement may persist or newly appear |
| Progression free Survival (PFS) | From enrollment to up to 2 years post-treatment | the time from randomization (or study entry) until objective disease progression or death from any cause, whichever occurs first as assessed using standardized tumor response criteria (RECIL) |
| Quality of Life (QoL) | at the end of treatment at 12 weeks | Quality of Life (QoL) defined and measured by EORTC QLQ-C30, a standardized, cancer-specific questionnaire developed by the European Organization for Research and Treatment of Cancer. |
| Adverse Events | From enrollment to the end of treatment at 12 weeks | Adverse events graded as per CTCAE version 5.0 * Haematological: anaemia, neutropenia, and thrombocytopenia * Non-haematological: renal dysfunction, hepatotoxicity, mucositis, nausea, and neuropathy |
Countries
Pakistan
Contacts
CONTACTInbsaat Iqbal, MBBS, MD
CONTACTHafiz Muhammad Ehsan Arshad, MBBS
STUDY_DIRECTORInbsaat Iqbal, MBBS, MD
King Edward Medical University
Outcome results
None listed