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

6 août 2026 mis à jour par: Abbas Khokhar, King Edward Medical University

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

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.

Aperçu de l'étude

Statut

Recrutement

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Estimé)

74

Phase

  • Phase 3

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Sauvegarde des contacts de l'étude

Lieux d'étude

  • Pakistan
    • Punjab Province
      • Lahore, Punjab Province, Pakistan, 54000
        • Recrutement
        • Mayo Hospital
        • Contact:
        • Contact:
        • Chercheur principal:
          • Inbsaat Iqbal, MBBS, MD
        • Sous-enquêteur:
          • Hafiz Muhammad Ehsan Arshad, MBBS

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

  • Adulte
  • Adulte plus âgé

Accepte les volontaires sains

Non

La description

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

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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.
Médicament: Cisplatin (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.
Médicament: Dexametasone
The standard dexamethasone dosing regimen per RECIL 2017 criteria
Autres noms:
  • Dexa
Médicament: Cytarabine (Ara-C) (Modified schedule)
The modified DHAP regimen alters the administration schedule of cisplatin and cytarabine. Cytarabine is administered over two consecutive days.
Comparateur actif: 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.
Médicament: 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.
Autres noms:
  • Cytarabine
  • la dexaméthasone
Médicament: Dexametasone
The standard dexamethasone dosing regimen per RECIL 2017 criteria
Autres noms:
  • Dexa
Médicament: Cytarabine (Ara-C)

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.
Autres noms:
  • Ara-C

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Overall Response rate (ORR)
Délai: 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
From enrollment to the end of treatment at 12 weeks

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Complete Response (CR)
Délai: 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
From enrollment to the end of treatment at 12 weeks
Partial Response (PR)
Délai: 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
From enrollment to the end of treatment at 12 weeks
Minor Response (MR)
Délai: 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
From enrollment to the end of treatment at 12 weeks
Stable Disease
Délai: 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
From enrollment to the end of treatment at 12 weeks
Progressive Disease
Délai: 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
From enrollment to the end of treatment at 12 weeks
Quality of Life (QoL)
Délai: 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.
at the end of treatment at 12 weeks
Progression free Survival (PFS)
Délai: 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)
From enrollment to up to 2 years post-treatment
Adverse Events
Délai: 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
From enrollment to the end of treatment at 12 weeks

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

King Edward Medical University

Les enquêteurs

  • Directeur d'études: Inbsaat Iqbal, MBBS, MD, King Edward Medical University

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

18 mars 2026

Achèvement primaire (Estimé)

20 mai 2027

Achèvement de l'étude (Estimé)

20 octobre 2027

Dates d'inscription aux études

Première soumission

28 juillet 2026

Première soumission répondant aux critères de contrôle qualité

28 juillet 2026

Première publication (Réel)

31 juillet 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

10 août 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

6 août 2026

Dernière vérification

1 août 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • KEMU-IRB-77-RC-2026

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

NON

Description du régime IPD

IPD will not be shared but could be provided by the principal investigator (PI) up on reasonable request

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

produit fabriqué et exporté des États-Unis.

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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