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

6 augustus 2026 bijgewerkt door: 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.

Studie Overzicht

Toestand

Werving

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Geschat)

74

Fase

  • Fase 3

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Contact Back-up

Studie Locaties

  • Pakistan
    • Punjab Province
      • Lahore, Punjab Province, Pakistan, 54000
        • Werving
        • Mayo Hospital
        • Contact:
        • Contact:
        • Hoofdonderzoeker:
          • Inbsaat Iqbal, MBBS, MD
        • Onderonderzoeker:
          • Hafiz Muhammad Ehsan Arshad, MBBS

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

  • Volwassen
  • Oudere volwassene

Accepteert gezonde vrijwilligers

Nee

Beschrijving

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

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: 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.
Geneesmiddel: 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.
Geneesmiddel: Dexametasone
The standard dexamethasone dosing regimen per RECIL 2017 criteria
Andere namen:
  • Dexa
Geneesmiddel: Cytarabine (Ara-C) (Modified schedule)
The modified DHAP regimen alters the administration schedule of cisplatin and cytarabine. Cytarabine is administered over two consecutive days.
Actieve vergelijker: 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.
Geneesmiddel: 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.
Andere namen:
  • Cytarabine
  • dexamethason
Geneesmiddel: Dexametasone
The standard dexamethasone dosing regimen per RECIL 2017 criteria
Andere namen:
  • Dexa
Geneesmiddel: 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.
Andere namen:
  • Ara-C

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Overall Response rate (ORR)
Tijdsspanne: 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

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Complete Response (CR)
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

King Edward Medical University

Onderzoekers

  • Studie directeur: Inbsaat Iqbal, MBBS, MD, King Edward Medical University

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

18 maart 2026

Primaire voltooiing (Geschat)

20 mei 2027

Studie voltooiing (Geschat)

20 oktober 2027

Studieregistratiedata

Eerst ingediend

28 juli 2026

Eerst ingediend dat voldeed aan de QC-criteria

28 juli 2026

Eerst geplaatst (Werkelijk)

31 juli 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

10 augustus 2026

Laatste update ingediend die voldeed aan QC-criteria

6 augustus 2026

Laatst geverifieerd

1 augustus 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • KEMU-IRB-77-RC-2026

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

NEE

Beschrijving IPD-plan

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

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

product vervaardigd in en geëxporteerd uit de V.S.

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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