Less Doses of Daratumumab Are Adequate to Achieve Response in Newly Diagnosed Multiple Myeloma

NCT07891923 | Recruiting Phase 2 DMC

• 1 other identifier: 901135
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical trial is to evaluate whether a modified (less frequent) dosing schedule of daratumumab, when added to standard VRd therapy, can be an effective induction regimen for treating newly diagnosed multiple myeloma (NDMM). The main questions it aims to answer are:

• Response assessment - A bone marrow test will be done within two weeks of end of cycle 4 in order to assess the cancer burden via a special test called MRD (minimal residual disease) in the bone marrow.
• Blood tests will be performed to assess your response to treatment (serum protein electrophoresis, immunofixation electrophoresis and serum free light chain assay) after cycle 2 (between day 51-day 56) and cycle 4 (between 107-112). These blood tests are routinely done for all myeloma patients during their treatment to assess response.

Conditions

Newly Diagnosed Multiple Myeloma (NDMM)

Keywords

newly diagnosed multiple myeloma; Less frequent daratumumab; Induction; Minimal residual disease (MRD); Pharmacokinetics; Prospective study; Interventional phase 2 study

Outcome Measures

Primary Outcomes (1)

• Post-induction MRD negativity rate

  Proportion of participants achieving measurable (minimal) residual disease (MRD) negativity at the end of four cycles of induction therapy with daratumumab, bortezomib, lenalidomide, and dexamethasone (Dara-VRd). MRD negativity will be assessed

  At the end of Cycle 4 (each induction cycle is 28 days; MRD assessed within 2 weeks after completion of Cycle 4 [approximately Days 113-127]

Secondary Outcomes (9)

• Overall Response Rate (ORR) and ≥Complete Response (≥CR) Rate After Four Cycles of Induction

  At the end of Cycle 4 (each induction cycle is 28 days; response assessed between Days 107 and 112).

• Overall Response Rate (ORR) and ≥Complete Response (≥CR) Rate Day 100 (±15 days) post-transplant

  Day 100 (±15 days) following autologous hematopoietic stem cell transplant

• Progression-Free Survival (PFS)

  From treatment initiation through 2 years of follow-up.

• Incidence of Grade ≥3 Adverse Events

  Up to 4 weeks after the last dose of study treatment.

• Minimal residual disease (MRD)Negativity at Day 100 (±15 Days) Post-Autologous Stem Cell Transplantation (ASCT)

  Day 100 (±15 days) following autologous stem cell transplantation (ASCT).

Study Arms (1)

Daratumumab with VRd (bortezomib lenalidomide and dexamethasone)

EXPERIMENTAL

Four cycles of induction Each cycle - 28 days Components of induction regimen 1. Less frequent daratumumab schedule as per Daratumumab: 16 mg/kg IV (Day1, Day 15, Day 29, Day 50, Day 71, Day 92) 2. Bortezomib: 1.3 mg/m² SC or IV, weekly 3. Lenalidomide: 15-25 mg orally, daily for 21 of 28 days 4. Dexamethasone: 40 mg weekly, orally or IV

Drug: Daratumumab (Intravenously) with VRd (Bortezomib, Lenalidomide, and Dexamethasone)

Interventions

Daratumumab (Intravenously) with VRd (Bortezomib, Lenalidomide, and Dexamethasone) DRUG

This arm includes newly diagnosed multiple myeloma (NDMM) patients who meet all inclusion and exclusion criteria. Patients will be administered 4 cycles of Dara-VRd induction. Each cycle will be of 28 days month. In each Dara-VRd cycle, Daratumumab will be administered at a dose of 16 mg/kg intravenously (Day1, Day 15, Day 29, Day 50, Day 71, Day 92), Bortezomib will be given weekly at a dose of 1.3 mg/m2 subcutaneous or intravenous, Lenalidomide will be given at a dose of 15-25 mg OD (21 days out of 28 days), and Dexamethasone 40mg once weekly - oral or intravenous.

Daratumumab with VRd (bortezomib lenalidomide and dexamethasone)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed multiple myeloma
• ECOG performance status 0-2
• Age ≥18 years of age
• Acceptable liver functions, as specified below: Total bilirubin \<2 times upper limit of normal (ULN), Aspartate transaminase (AST; SGOT), alanine transaminase (ALT; SGPT) \<3 ULN
• Acceptable hematological parameters: Hemoglobin \>7g/dl, Absolute neutrophil count (ANC) ≥500/mm3, platelet count ≥50,000/mm3
• Creatinine clearance ≥30ml/minute (by Cockcroft-Gault formula)
• Treatment naive or received ≤ 1 cycle (≤28 days) of bortezomib based triplet therapy

You may not qualify if:

• Other plasma cell dyscrasias - Plasma cell leukemia (\>=5% circulating plasma cells in peripheral blood), AL Amyloidosis, POEMS syndrome
• Patients with symptomatic central nervous system involvement (as per assessing clinician)
• Patients with symptomatic obstructive airway disease, as per assessing clinician
• New York Heart Association (NYHA) Class III or IV cardiac disease, or left ventricular ejection fraction \<40%
• Human immunodeficiency virus (HIV) positive or HBsAg positive
• Pregnant or breastfeeding female

Sponsors & Collaborators

• Tata Memorial Centre: lead
• Indian Council of Medical Research: collaborator

Study Sites (2)

Actrec Tmc

Navi Mumbai, Maharashtra, 410210, India

RECRUITING

Dr.Sumeet Mirgh

Navi Mumbai, Maharashtra, 410210, India

NOT YET RECRUITING

Related Publications (22)

• Tembhare P, Bagal B, Sriram H, et al. Concordance between peripheral blood MRD, bone marrow MRD and serum immunofixation in newly diagnosed multiple myeloma. ISLH 2024. https://onlinelibrary.wiley.com/doi/10.1111/ijlh.14396

  RESULT

• Medina A, Puig N, Flores-Montero J, Jimenez C, Sarasquete ME, Garcia-Alvarez M, Prieto-Conde I, Chillon C, Alcoceba M, Gutierrez NC, Oriol A, Rosinol L, Blade J, Gironella M, Hernandez MT, Gonzalez-Calle V, Cedena MT, Paiva B, San-Miguel JF, Lahuerta JJ, Mateos MV, Martinez-Lopez J, Orfao A, Gonzalez M, Garcia-Sanz R. Comparison of next-generation sequencing (NGS) and next-generation flow (NGF) for minimal residual disease (MRD) assessment in multiple myeloma. Blood Cancer J. 2020 Oct 30;10(10):108. doi: 10.1038/s41408-020-00377-0.

  PMID: 33127891 RESULT

• Paiva B, Puig N, Cedena MT, Rosinol L, Cordon L, Vidriales MB, Burgos L, Flores-Montero J, Sanoja-Flores L, Lopez-Anglada L, Maldonado R, de la Cruz J, Gutierrez NC, Calasanz MJ, Martin-Ramos ML, Garcia-Sanz R, Martinez-Lopez J, Oriol A, Blanchard MJ, Rios R, Martin J, Martinez-Martinez R, Sureda A, Hernandez MT, de la Rubia J, Krsnik I, Moraleda JM, Palomera L, Bargay J, Van Dongen JJM, Orfao A, Mateos MV, Blade J, San-Miguel JF, Lahuerta JJ; GEM (Grupo Espanol de Mieloma)/PETHEMA (Programa Para el Estudio de la Terapeutica en Hemopatias Malignas) Cooperative Study Group. Measurable Residual Disease by Next-Generation Flow Cytometry in Multiple Myeloma. J Clin Oncol. 2020 Mar 10;38(8):784-792. doi: 10.1200/JCO.19.01231. Epub 2019 Nov 26.

  PMID: 31770060 RESULT

• US Department of Health and Human Services, National Institutes of Health, National Cancer Institute (2017) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 2017. https://ctep.cancer.gov/ protocolDevelopment/electronic_applications/docs/ CTCAE_v5_Quick_Reference_8.5x11.pdf. Accessed 01 May 2020

  RESULT

• Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, Munshi N, Lonial S, Blade J, Mateos MV, Dimopoulos M, Kastritis E, Boccadoro M, Orlowski R, Goldschmidt H, Spencer A, Hou J, Chng WJ, Usmani SZ, Zamagni E, Shimizu K, Jagannath S, Johnsen HE, Terpos E, Reiman A, Kyle RA, Sonneveld P, Richardson PG, McCarthy P, Ludwig H, Chen W, Cavo M, Harousseau JL, Lentzsch S, Hillengass J, Palumbo A, Orfao A, Rajkumar SV, Miguel JS, Avet-Loiseau H. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016 Aug;17(8):e328-e346. doi: 10.1016/S1470-2045(16)30206-6.

  PMID: 27511158 RESULT

• Tembhare PR, Sriram H, Chatterjee G, Khanka T, Gokarn A, Mirgh S, Rajendra A, Chaturvedi A, Ghogale SG, Deshpande N, Girase K, Dalvi K, Rajpal S, Patkar N, Trivedi B, Joshi A, Murthy V, Shetty N, Nair S, More A, Kamtalwar S, Chavan P, Bhat V, Bhat P, Subramanian PG, Gupta S, Khattry N. Comprehensive immune cell profiling depicts an early immune response associated with severe coronavirus disease 2019 in cancer patients. Immunol Cell Biol. 2022 Jan;100(1):61-73. doi: 10.1111/imcb.12504. Epub 2021 Oct 27.

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• Mai EK, Hielscher T, Bertsch U, Salwender HJ, Zweegman S, Raab MS, Munder M, Pantani L, Mancuso K, Brossart P, Beksac M, Blau IW, Durig J, Besemer B, Fenk R, Reimer P, van der Holt B, Hanel M, von Metzler I, Graeven U, Muller-Tidow C, Boccadoro M, Scheid C, Dimopoulos MA, Hillengass J, Weisel KC, Cavo M, Sonneveld P, Goldschmidt H. Predictors of early morbidity and mortality in newly diagnosed multiple myeloma: data from five randomized, controlled, phase III trials in 3700 patients. Leukemia. 2024 Mar;38(3):640-647. doi: 10.1038/s41375-023-02105-6. Epub 2023 Dec 7.

  PMID: 38062124 RESULT

• Palumbo A, Chanan-Khan A, Weisel K, Nooka AK, Masszi T, Beksac M, Spicka I, Hungria V, Munder M, Mateos MV, Mark TM, Qi M, Schecter J, Amin H, Qin X, Deraedt W, Ahmadi T, Spencer A, Sonneveld P; CASTOR Investigators. Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016 Aug 25;375(8):754-66. doi: 10.1056/NEJMoa1606038.

  PMID: 27557302 RESULT

• Plesner T, Arkenau HT, Gimsing P, Krejcik J, Lemech C, Minnema MC, Lassen U, Laubach JP, Palumbo A, Lisby S, Basse L, Wang J, Sasser AK, Guckert ME, de Boer C, Khokhar NZ, Yeh H, Clemens PL, Ahmadi T, Lokhorst HM, Richardson PG. Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma. Blood. 2016 Oct 6;128(14):1821-1828. doi: 10.1182/blood-2016-07-726729. Epub 2016 Aug 16.

  PMID: 27531679 RESULT

• Clemens PL, Yan X, Lokhorst HM, Lonial S, Losic N, Khan I, Jansson R, Ahmadi T, Lantz K, Zhou H, Puchalski T, Xu XS. Pharmacokinetics of Daratumumab Following Intravenous Infusion in Relapsed or Refractory Multiple Myeloma After Prior Proteasome Inhibitor and Immunomodulatory Drug Treatment. Clin Pharmacokinet. 2017 Aug;56(8):915-924. doi: 10.1007/s40262-016-0477-1.

  PMID: 27896689 RESULT

• Xu XS, Yan X, Puchalski T, Lonial S, Lokhorst HM, Voorhees PM, Plesner T, Liu K, Khan I, Jansson R, Ahmadi T, Ruixo JP, Zhou H, Clemens PL. Clinical Implications of Complex Pharmacokinetics for Daratumumab Dose Regimen in Patients With Relapsed/Refractory Multiple Myeloma. Clin Pharmacol Ther. 2017 Jun;101(6):721-724. doi: 10.1002/cpt.577. Epub 2017 Feb 13.

  PMID: 27859027 RESULT

• Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, Rabin N, Orlowski RZ, Komarnicki M, Suzuki K, Plesner T, Yoon SS, Ben Yehuda D, Richardson PG, Goldschmidt H, Reece D, Lisby S, Khokhar NZ, O'Rourke L, Chiu C, Qin X, Guckert M, Ahmadi T, Moreau P; POLLUX Investigators. Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016 Oct 6;375(14):1319-1331. doi: 10.1056/NEJMoa1607751.

  PMID: 27705267 RESULT

• Dimopoulos MA, Terpos E, Boccadoro M, Delimpasi S, Beksac M, Katodritou E, Moreau P, Baldini L, Symeonidis A, Bila J, Oriol A, Mateos MV, Einsele H, Orfanidis I, Ahmadi T, Ukropec J, Kampfenkel T, Schecter JM, Qiu Y, Amin H, Vermeulen J, Carson R, Sonneveld P; APOLLO Trial Investigators. Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Jun;22(6):801-812. doi: 10.1016/S1470-2045(21)00128-5.

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• Chim CS, Kumar S, Wong VKC, Ngai C, Kwong YL. 3-weekly daratumumab-lenalidomide/pomalidomide-dexamethasone is highly effective in relapsed and refractory multiple myeloma. Hematology. 2021 Dec;26(1):652-655. doi: 10.1080/16078454.2021.1965737.

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• Lokhorst HM, Plesner T, Laubach JP, Nahi H, Gimsing P, Hansson M, Minnema MC, Lassen U, Krejcik J, Palumbo A, van de Donk NW, Ahmadi T, Khan I, Uhlar CM, Wang J, Sasser AK, Losic N, Lisby S, Basse L, Brun N, Richardson PG. Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma. N Engl J Med. 2015 Sep 24;373(13):1207-19. doi: 10.1056/NEJMoa1506348. Epub 2015 Aug 26.

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• Attal M, Lauwers-Cances V, Hulin C, Leleu X, Caillot D, Escoffre M, Arnulf B, Macro M, Belhadj K, Garderet L, Roussel M, Payen C, Mathiot C, Fermand JP, Meuleman N, Rollet S, Maglio ME, Zeytoonjian AA, Weller EA, Munshi N, Anderson KC, Richardson PG, Facon T, Avet-Loiseau H, Harousseau JL, Moreau P; IFM 2009 Study. Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma. N Engl J Med. 2017 Apr 6;376(14):1311-1320. doi: 10.1056/NEJMoa1611750.

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  PMID: 30831554 RESULT

MeSH Terms

Conditions

Neoplasm, Residual

Interventions

daratumumab; Bortezomib; Lenalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Central Study Contacts

Dr.Sumeet Mirgh, MBBS MD DM Clinical Hematology

CONTACT

+91 8130140245; drsumeetmirgh@gmail.com

Dr. Anant Gokarn, MBBS MD DM Medical Oncology

CONTACT

+91 8097295540; anantgokarn@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 11, 2026
• First Posted: October 23, 2026
• Study Start: October 28, 2025
• Primary Completion (Estimated): May 5, 2029
• Study Completion (Estimated): May 5, 2029
• Last Updated: October 23, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will not share

Locations

IN (2)