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出境医 / 临床实验 / Study of Daratumumab in Multiple Myeloma (MM) Patients in >VGPR/MRD-positive (DART4MM)

Study of Daratumumab in Multiple Myeloma (MM) Patients in >VGPR/MRD-positive (DART4MM)

Study Description
Brief Summary:
Aim of this study is to evaluate Daratumumab effect on MRD-positive patients with Multiple Myeloma (MM) who achieved >VGPR after any therapy (ASCT, VMP, Rev-Dex). Daratumumab 16 mg/kg administered at weekly intervals for 8 weeks, then every 2 weeks for an additional 16 weeks, will be given to 50 MM patients who achieved a >VGPR defined by monoclonal component disappearance in serum or urine, immunofixation positive/negative and MRD-positivity (by NGF). Free light chain (FLC) and CT/PET will be evaluated at time 0. NGF will be done on marrow aspirate at time 0, at 2 months and every 6 months for 2 years. If patients will be still MRD positive after 6 months of therapy , treatment will be continued up to 2 years. If MRD negative by NGF, the patients can stop the treatment.

Condition or disease Intervention/treatment Phase
Myeloma Multiple Drug: Daratumumab Phase 2

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Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Patients will receive Daratumumab (16 mg/Kg day) every week for 8 weeks intravenous (8 infusions) and then every 2 weeks for 16 weeks intravenous (8 more infusions).

If MRD positive by NGF, the patients will receive Daratumumab every 4 weeks for 80 weeks intravenous; if MRD negative by NGF, the patients can stop the treatment.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study on the Efficacy of Daratumumab in Multiple Myeloma (MM) Patients in >VGPR/MRD-positive by Next Generation Flow
Actual Study Start Date : December 31, 2018
Estimated Primary Completion Date : June 30, 2022
Estimated Study Completion Date : December 31, 2022
Arms and Interventions
Arm Intervention/treatment
Experimental: Single Arm

Patients will receive Daratumumab (16 mg/Kg day) every week for 8 weeks intravenous (8 infusions) and then every 2 weeks for 16 weeks intravenous (8 more infusions).

If MRD positive by NGF, the patients will receive Daratumumab every 4 weeks for 80 weeks intravenous; if MRD negative by NGF, the patients can stop the treatment.

 Drug: Daratumumab
Daratumumab is a human monoclonal antibody (mAb) IgG1 that binds to the highly expressed CD38 protein on the surface of multiple myeloma cells and, at various levels, also in other types of cells and tissues. The CD38 protein has multiple functions, such as receptor-mediated adhesion, signal transduction activity and enzymatic activity.
Other Name: Darzalex
Outcome Measures
Primary Outcome Measures :
  1. Overall Responde Rate (ORR) [ Time Frame: every 6 months ]
    The fraction of patients who experience a Minimal Residual Disease (MRD) negativity per IMWG 2016 criteria


Secondary Outcome Measures :
  1. Progression free survival (PFS) [ Time Frame: every 6 months ]
    PFS determined using the Kaplan-Meier method, considering those who progress or die without progression as failures, and censoring those who do not

  2. Complete Remission Rate (CR) [ Time Frame: every 6 months ]
    The fraction of patient who experience a sCR using the study treatment

  3. Duration of Response (DoR) [ Time Frame: every 6 months ]
    The fraction of patients who continues to respond to treatment without Myeloma progression


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Able to adhere to the study visit schedule and other protocol requirements
  • >VGPR/MRD-positive by NGF measured by 2-tubes optimized 8-color antibody panel, (OneFlow PCST e PCD BD Biosciences)
  • Patients should be at enrollment at least 12 weeks from any therapy for myeloma after diagnosis or at any subsequent relapse
  • Eastern Cooperative Oncology Group performance status score of 0, 1, or 2
  • Laboratory values and electrocardiogram within protocol-defined parameters at screening
  • All previous MM therapy, including radiation, cytostatic therapy and surgery, must have been terminated at least 4 weeks prior to treatment in this study, without corticosteroid therapy.

  • Laboratory test results within these ranges:

    • Absolute neutrophil count 1.0 x 109/L
    • Platelet count 75 x 109/L
    • Creatinine clearance > 30 ml/h)
    • Total bilirubin 1.5 mg/Dl
    • Aspartate aminotransferase (AST; SGOT) and alanine aminotransferase (ALT; SGPT) 2 x ULN
  • Disease free of prior malignancies for 5 years with exception of curatively treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast
  • Fertile patients must use effective contraception during and for 6 months after study treatment
  • Patients must sign on an Informed Consent Form No study treatment or any other procedure within the framework of the trial (except for screening) will be performed in any patient prior to receipt of written informed consent.

Exclusion Criteria:

  • Received Daratumumab or other anti-CD38 therapies previously
  • Nonsecretory multiple myeloma
  • Previously received an allogenic stem cell transplant or has received an autologous stem cell transplantation within 12 weeks
  • Known chronic obstructive pulmonary disease, persistent asthma, or a history of asthma within 5 years
  • Absence of the Informed Consent Form signed by the patient
  • Pregnant or breast feeding females
  • Use of any other experimental drug or therapy within 28 days of baseline.
  • Known hypersensitivity to the study drugs
  • Known positive for human immunodeficiency virus (HIV) or infectious hepatitis, type A, B or C.
  • Plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or amyloidosis
Contacts and Locations

Contacts
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Contact: Cristiana Cafarelli, Letters 0039 0577586718 cristianacafarelli21@gmail.com
Contact: Francesca Di Martino, Pharmacy 0039 0577586798 francesca.dimartino29@gmail.com

Locations
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Italy
Azienda Ospedaliera Universitaria Senese Recruiting
Siena, Italy, 53100
Contact: Cristiana Cafarelli, Letters    0039 0577586718    cristianacafarelli21@gmail.com   
Contact: Francesca Di Martino, Pharmacy    0039 0577586798    francesca.dimartino29@gmail.com   
Principal Investigator: Alessandro Gozzetti, Medicine         
Sub-Investigator: Francesca Bacchiarri, Medicine         
Sponsors and Collaborators
Azienda Ospedaliera Universitaria Senese
Janssen-Cilag S.p.A.
Investigators
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Principal Investigator: Alessandro Gozzetti, Medicine Azienda Ospedaliera Universitaria Senese
Tracking Information
First Submitted Date  ICMJE June 3, 2019
First Posted Date  ICMJE June 20, 2019
Last Update Posted Date June 20, 2019
Actual Study Start Date  ICMJE December 31, 2018
Estimated Primary Completion Date June 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 17, 2019) 		Overall Responde Rate (ORR) [ Time Frame: every 6 months ]
The fraction of patients who experience a Minimal Residual Disease (MRD) negativity per IMWG 2016 criteria
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: June 17, 2019)
  • Progression free survival (PFS) [ Time Frame: every 6 months ]
    PFS determined using the Kaplan-Meier method, considering those who progress or die without progression as failures, and censoring those who do not
  • Complete Remission Rate (CR) [ Time Frame: every 6 months ]
    The fraction of patient who experience a sCR using the study treatment
  • Duration of Response (DoR) [ Time Frame: every 6 months ]
    The fraction of patients who continues to respond to treatment without Myeloma progression
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Daratumumab in Multiple Myeloma (MM) Patients in >VGPR/MRD-positive
Official Title  ICMJE A Pilot Study on the Efficacy of Daratumumab in Multiple Myeloma (MM) Patients in >VGPR/MRD-positive by Next Generation Flow
Brief Summary Aim of this study is to evaluate Daratumumab effect on MRD-positive patients with Multiple Myeloma (MM) who achieved >VGPR after any therapy (ASCT, VMP, Rev-Dex). Daratumumab 16 mg/kg administered at weekly intervals for 8 weeks, then every 2 weeks for an additional 16 weeks, will be given to 50 MM patients who achieved a >VGPR defined by monoclonal component disappearance in serum or urine, immunofixation positive/negative and MRD-positivity (by NGF). Free light chain (FLC) and CT/PET will be evaluated at time 0. NGF will be done on marrow aspirate at time 0, at 2 months and every 6 months for 2 years. If patients will be still MRD positive after 6 months of therapy , treatment will be continued up to 2 years. If MRD negative by NGF, the patients can stop the treatment.
Detailed Description

Daratumumab in clinical trials and study rationale Daratumumab is an immunoglobulin G1 kappa (IgG1κ) human mAb against CD 38 antigen, produced in a mammalian cell line (CHO) using recombinant DNA technology. (see Investigational Brochure, IB) Daratumumab has been explored as a single agent in relapsed and refractory patients (GEN501,NCT00574288. In the dose-expansion phase 30 patients received 8 mg/kg and 42 patients 16 mg/kg once weekly (8 doses), twice monthly (8 doses) then monthly up to 24 months. Patients had received a median number of 4 to 5 lines of therapy with 54% of patients refractory to bortezomib and 72% to lenalidomide. Low grade infusion-related reactions were initially observed in up to 75% of patients but were considerably attenuated by the delivery in a large infusion volume. Thirty five percent of patients receiving a dose of 16 mg/kg responded, with 15% of complete or very good partial responses. These encouraging results were confirmed in the multicenter phase 2 study SIRIUS (NCT01985126). In this study, 106 heavily pretreated myeloma patients received daratumumab monotherapy (16 mg/kg). Patients had received a median of 5 prior therapies and the majority of them were refractory to bortezomib, lenalidomide and pomalidomide. Partial response was achieved by 29.2% of patients and the median duration of response was 7.4 months.

A pooled analysis of the patients of the GEN 501 and the SIRIUS trials who had received daratumumab monotherapy at the dose of 16 mg/kg (n=148) showed an overall response rate of 31.1% and a median PFS and OS of 4 and 20 months, respectively. Patients achieving only stable disease or minimal response reached a promising median overall survival of 18.5 months, which is unexpected in this population of very advanced myeloma patients. The quality of response was correlated with the expression intensity of CD38 by neoplastic plasmocytes. Daratumumab was granted accelerated approval in 2015 by the FDA to treat patients with multiple myeloma who had received at least three prior treatments. Daratumumab is also being studied in combination with many other agents including lenalidomide, bortezomib, carfilzomib or pomalidomide. The phase 3 randomized trial CASTOR recently confirmed a strong advantage of the addition of daratumumab to bortezomib/dexamethasone, in 498 relapsed myeloma patients (NCT02136134). The triplet combination was associated with a significantly better response rate, including 82.9% of PR or better and 19.2% of CR or better. The 1-year rate of progression free survival was 60.7% in the daratumumab group versus 26.9% in the control arm. The updated results of this trial have confirmed this strong PFS benefit for the patients in the daratumumab arm, especially for the patients in first relapse (12-months PFS : 77.3% vs 24.7%, p<10-4). Daratumumab also clearly improved the median PFS of patients with high-risk cytogenetic. In this relapse setting, the POLLUX trial also demonstrated a strong advantage of the addition of daratumumab to lenalidomide and dexamethasone, in terms of both response rate and PFS (NCT02076009) . In this trial, patients in the daratumumab group reached an overall response rate of 93% (including 43% CR) and had a 63% reduction in the risk of progression. The updated results of this trial confirmed this significant PFS advantage even in lenalidomide-naïve patients and in patients with high-risk cytogenetic. Minimal Residual disease (MRD) assessed by NGS analysis in patients included in CASTOR and POLLUX trials revealed an unprecedently observed rate of patients with MRD negative disease. Indeed, 32% (vs 9%) and 18% (vs 4%) of patients reached a 10-4 MRD negative in the daratumumab (versus control) arms of POLLUX and CASTOR, respectively. In particular the rate of MRD negativity (10-5) has increased continuosly after month 6 in patients receiving Daratumumab monotherapy in the CASTOR trial. (36) The addition of daratumumab is currently being assessed in the context of previously untreated myeloma patients. The phase 3 randomized study Cassiopeia is currently evaluating the role of daratumumab in combination with VTD in induction, and its role as maintenance after high-dose therapy (NCT02541383). In patients not eligible for transplant, the phase 3 randomized trial MAIA is evaluating the addition of daratumumab to lenalidomide-dexamethasone (NCT02252172). In the ALCYONE trial (Dara-VMP vs VMP) in patients inelegible to transplant MRD negativity (10-5) has increased continuosly after cycle 10 with daratumumab monotherapy.(37) The potential benefit of daratumumab has also been recently evaluated in high-risk smoldering myeloma patients in the phase 3 randomized CENTAURUS (NCT02316106). Daratumumab monotherapy can increase response and in particular MRD negativity, which correlates with PFS and OS. To the investigator's knowledge the use of daratumumab in multiple myeloma patients with suboptimal response (in particular with a >VGPR/MRD+) has not yet been explored. To achieve a better response can ameliorate patient outcome and survival.

DATA COLLECTION All patient-related data are recorded in a pseudonomized way. Each patient is unequivocally identified by a trial subject number, attributed at recruitment into the study. The investigator has to keep a patient identification log, including the full name and address of the subject and eventually additional relevant personal data such as hospital record number, home physician etc. In addition, patients who were screened in order to be entered into the study, but who could not be recruited for whatever reason (informed consent not given, not fulfilling selection criteria etc.) are recorded in a "patient reject log". All the data retrieved during the conduct of the study are entered into the appropriate case record forms (CRF) by the investigator or another person authorized by the investigator (co-investigator). The CRFs are provided by the study secretariat and are explained to the investigator by the study monitor.

SAMPLE SIZE CALCULATION The main objective of the trial is to assess, whether the experimental regimen shows a promising activity profile in treatment of MM minimal residual disease. The primary endpoint is the response rate. Multiple myeloma patients achieving CR and MRD negativity after autotransplant are around 60% and 20% of the total, respectively. MM patients that achieve an MRD negative status after VMP (velcade , melphalan prednisone) are not known. Since CR achievement after VMP is 30%, MRD negativity is probably < 5% of the patients. Statistical analysis will be provided on 50 patients, assuming the power to show an increase in MRD negativity from 20% to at least 50% of the patients treated. In summary, the trial design is based on the following assumptions: The activity of the experimental therapy would be rated as insufficient, if the actual response rate was only 20% or lower. On the other hand, the regimen would be considered to be a promising candidate for further development (e.g. in a phase III trial), if the true ORR amounted to 50% or more. To show effectiveness of daratumumab to give a negative MRD; only descriptive statistics will be performed AE RECORDING All adverse events and special reporting situations, whether serious or non-serious, will be reported from the time a signed and dated ICF is obtained until completion of the subject's last study-related procedure, which may include contact for follow-up of safety. Serious adverse events, including those spontaneously reported to the investigator within 30 days after the last dose of study drug, must be reported using the Serious Adverse Event Form. The sponsor will evaluate any safety information that is spontaneously reported by an investigator beyond the time frame specified in the protocol.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Patients will receive Daratumumab (16 mg/Kg day) every week for 8 weeks intravenous (8 infusions) and then every 2 weeks for 16 weeks intravenous (8 more infusions).

If MRD positive by NGF, the patients will receive Daratumumab every 4 weeks for 80 weeks intravenous; if MRD negative by NGF, the patients can stop the treatment.

Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Myeloma Multiple
Intervention  ICMJE Drug: Daratumumab
Daratumumab is a human monoclonal antibody (mAb) IgG1 that binds to the highly expressed CD38 protein on the surface of multiple myeloma cells and, at various levels, also in other types of cells and tissues. The CD38 protein has multiple functions, such as receptor-mediated adhesion, signal transduction activity and enzymatic activity.
Other Name: Darzalex
Study Arms  ICMJE Experimental: Single Arm

Patients will receive Daratumumab (16 mg/Kg day) every week for 8 weeks intravenous (8 infusions) and then every 2 weeks for 16 weeks intravenous (8 more infusions).

If MRD positive by NGF, the patients will receive Daratumumab every 4 weeks for 80 weeks intravenous; if MRD negative by NGF, the patients can stop the treatment.

Intervention: Drug: Daratumumab
Publications *
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  • Wijermans P, Schaafsma M, Termorshuizen F, Ammerlaan R, Wittebol S, Sinnige H, Zweegman S, van Marwijk Kooy M, van der Griend R, Lokhorst H, Sonneveld P; Dutch-Belgium Cooperative Group HOVON. Phase III study of the value of thalidomide added to melphalan plus prednisone in elderly patients with newly diagnosed multiple myeloma: the HOVON 49 Study. J Clin Oncol. 2010 Jul 1;28(19):3160-6. doi: 10.1200/JCO.2009.26.1610. Epub 2010 Jun 1.
  • Hulin C, Facon T, Rodon P, Pegourie B, Benboubker L, Doyen C, Dib M, Guillerm G, Salles B, Eschard JP, Lenain P, Casassus P, Azaïs I, Decaux O, Garderet L, Mathiot C, Fontan J, Lafon I, Virion JM, Moreau P. Efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed multiple myeloma: IFM 01/01 trial. J Clin Oncol. 2009 Aug 1;27(22):3664-70. doi: 10.1200/JCO.2008.21.0948. Epub 2009 May 18.
  • Waage A, Gimsing P, Fayers P, Abildgaard N, Ahlberg L, Björkstrand B, Carlson K, Dahl IM, Forsberg K, Gulbrandsen N, Haukås E, Hjertner O, Hjorth M, Karlsson T, Knudsen LM, Nielsen JL, Linder O, Mellqvist UH, Nesthus I, Rolke J, Strandberg M, Sørbø JH, Wisløff F, Juliusson G, Turesson I; Nordic Myeloma Study Group. Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma. Blood. 2010 Sep 2;116(9):1405-12. doi: 10.1182/blood-2009-08-237974. Epub 2010 May 6.
  • Beksac M, Haznedar R, Firatli-Tuglular T, Ozdogu H, Aydogdu I, Konuk N, Sucak G, Kaygusuz I, Karakus S, Kaya E, Ali R, Gulbas Z, Ozet G, Goker H, Undar L. Addition of thalidomide to oral melphalan/prednisone in patients with multiple myeloma not eligible for transplantation: results of a randomized trial from the Turkish Myeloma Study Group. Eur J Haematol. 2011 Jan;86(1):16-22. doi: 10.1111/j.1600-0609.2010.01524.x. Epub 2010 Nov 22.
  • Fayers PM, Palumbo A, Hulin C, Waage A, Wijermans P, Beksaç M, Bringhen S, Mary JY, Gimsing P, Termorshuizen F, Haznedar R, Caravita T, Moreau P, Turesson I, Musto P, Benboubker L, Schaafsma M, Sonneveld P, Facon T; Nordic Myeloma Study Group; Italian Multiple Myeloma Network; Turkish Myeloma Study Group; Hemato-Oncologie voor Volwassenen Nederland; Intergroupe Francophone du Myélome; European Myeloma Network. Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials. Blood. 2011 Aug 4;118(5):1239-47. doi: 10.1182/blood-2011-03-341669. Epub 2011 Jun 13.
  • Morgan GJ, Davies FE, Gregory WM, Russell NH, Bell SE, Szubert AJ, Navarro Coy N, Cook G, Feyler S, Byrne JL, Roddie H, Rudin C, Drayson MT, Owen RG, Ross FM, Jackson GH, Child JA; NCRI Haematological Oncology Study Group. Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation. Blood. 2011 Aug 4;118(5):1231-8. doi: 10.1182/blood-2011-02-338665. Epub 2011 Jun 7.
  • San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, Spicka I, Petrucci MT, Palumbo A, Samoilova OS, Dmoszynska A, Abdulkadyrov KM, Schots R, Jiang B, Mateos MV, Anderson KC, Esseltine DL, Liu K, Cakana A, van de Velde H, Richardson PG; VISTA Trial Investigators. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 2008 Aug 28;359(9):906-17. doi: 10.1056/NEJMoa0801479.
  • Bringhen S, Larocca A, Rossi D, Cavalli M, Genuardi M, Ria R, Gentili S, Patriarca F, Nozzoli C, Levi A, Guglielmelli T, Benevolo G, Callea V, Rizzo V, Cangialosi C, Musto P, De Rosa L, Liberati AM, Grasso M, Falcone AP, Evangelista A, Cavo M, Gaidano G, Boccadoro M, Palumbo A. Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood. 2010 Dec 2;116(23):4745-53. doi: 10.1182/blood-2010-07-294983. Epub 2010 Aug 31. Erratum in: Blood. 2012 Dec 20;120(26):5250.
  • 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.
  • Reeder CB, Reece DE, Kukreti V, Chen C, Trudel S, Laumann K, Hentz J, Pirooz NA, Piza JG, Tiedemann R, Mikhael JR, Bergsagel PL, Leis JF, Fonseca R, Stewart AK. Once- versus twice-weekly bortezomib induction therapy with CyBorD in newly diagnosed multiple myeloma. Blood. 2010 Apr 22;115(16):3416-7. doi: 10.1182/blood-2010-02-271676.
  • Mateos MV, Dimopoulos MA, Cavo M, Suzuki K, Jakubowiak A, Knop S, Doyen C, Lucio P, Nagy Z, Kaplan P, Pour L, Cook M, Grosicki S, Crepaldi A, Liberati AM, Campbell P, Shelekhova T, Yoon SS, Iosava G, Fujisaki T, Garg M, Chiu C, Wang J, Carson R, Crist W, Deraedt W, Nguyen H, Qi M, San-Miguel J; ALCYONE Trial Investigators. Daratumumab plus Bortezomib, Melphalan, and Prednisone for Untreated Myeloma. N Engl J Med. 2018 Feb 8;378(6):518-528. doi: 10.1056/NEJMoa1714678. Epub 2017 Dec 12.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 17, 2019) 		50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2022
Estimated Primary Completion Date June 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Able to adhere to the study visit schedule and other protocol requirements
  • >VGPR/MRD-positive by NGF measured by 2-tubes optimized 8-color antibody panel, (OneFlow PCST e PCD BD Biosciences)
  • Patients should be at enrollment at least 12 weeks from any therapy for myeloma after diagnosis or at any subsequent relapse
  • Eastern Cooperative Oncology Group performance status score of 0, 1, or 2
  • Laboratory values and electrocardiogram within protocol-defined parameters at screening
  • All previous MM therapy, including radiation, cytostatic therapy and surgery, must have been terminated at least 4 weeks prior to treatment in this study, without corticosteroid therapy.

  • Laboratory test results within these ranges:

    • Absolute neutrophil count 1.0 x 109/L
    • Platelet count 75 x 109/L
    • Creatinine clearance > 30 ml/h)
    • Total bilirubin 1.5 mg/Dl
    • Aspartate aminotransferase (AST; SGOT) and alanine aminotransferase (ALT; SGPT) 2 x ULN
  • Disease free of prior malignancies for 5 years with exception of curatively treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast
  • Fertile patients must use effective contraception during and for 6 months after study treatment
  • Patients must sign on an Informed Consent Form No study treatment or any other procedure within the framework of the trial (except for screening) will be performed in any patient prior to receipt of written informed consent.

Exclusion Criteria:

  • Received Daratumumab or other anti-CD38 therapies previously
  • Nonsecretory multiple myeloma
  • Previously received an allogenic stem cell transplant or has received an autologous stem cell transplantation within 12 weeks
  • Known chronic obstructive pulmonary disease, persistent asthma, or a history of asthma within 5 years
  • Absence of the Informed Consent Form signed by the patient
  • Pregnant or breast feeding females
  • Use of any other experimental drug or therapy within 28 days of baseline.
  • Known hypersensitivity to the study drugs
  • Known positive for human immunodeficiency virus (HIV) or infectious hepatitis, type A, B or C.
  • Plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or amyloidosis
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Cristiana Cafarelli, Letters 0039 0577586718 cristianacafarelli21@gmail.com
Contact: Francesca Di Martino, Pharmacy 0039 0577586798 francesca.dimartino29@gmail.com
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03992170
Other Study ID Numbers  ICMJE DART4MM
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Alessandro Gozzetti, Azienda Ospedaliera Universitaria Senese
Study Sponsor  ICMJE Azienda Ospedaliera Universitaria Senese
Collaborators  ICMJE Janssen-Cilag S.p.A.
Investigators  ICMJE
Principal Investigator: Alessandro Gozzetti, Medicine Azienda Ospedaliera Universitaria Senese
PRS Account Azienda Ospedaliera Universitaria Senese
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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