Daratumumab Intensified Treatment to Eligible MM New Patients CTD-Dara Induction, Follow by Dara Consolidation

NCT03792620 | Unknown Phase 3 DMC FDA Drug FDA Device

• 2 other identifiers: U1111-1219-9010CAAE
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The best induction protocol to eligible multiple myeloma patients was not established. Combination of three drugs demonstrated better outcomes than two drugs combo. Nevertheless, until now four drugs combo did not prove gain against three drugs One of the three drugs protocol studied as induction was CTD scheme (cyclophosphamide+ thalidomide+dexamethasone). Daratumumab has a novel mechanism of action that results in enhanced activity in combination with existing standards of care, including first-generation novel agents, such as thalidomide, as well as other therapeutics. Considerable responses have been observed in a cohort of heavily pretreated patients with relapsed/refractory MM. The use of a treatment combination with monoclonal antibody associated with immunomodulator (in a four drug combo) can lead to a improvement in response rates and in survival, reflects on a better free time interval. This trial will represent a new option of treatment with a combination of anti CD38 monoclonal antibody (DARATUMUMAB) as induction regimen with CTD protocol (four drug combination). And It use as consolidation and maintenance to give better immunomodulatory response and extended survival and disease control.

Conditions

Multiple Myeloma Stage I

Keywords

multiple myeloma

Outcome Measures

Primary Outcomes (1)

• Incidence of response rate better than very good partial response after ASCT

  Number of patients that obtained better than VGPR after ASCT based on the IMWG description

  8 months after starting treatment

Secondary Outcomes (14)

• Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v 4.0

  24 months

• Incidence of Overall response rate

  24 months

• Duration of response after Dara-CTD treatment

  24 months

• Time of response after Dara-CTD treatment

  24 months

• Incidence of Minimal residual disease evaluate by PET CT image

  24 months

Study Arms (1)

Cyclo Thal Dex Daratumumab

EXPERIMENTAL

Eligible patients will be enrolled and treated according to the following elicited schema: Cyclo Thal Dex- Daratumumab (cyclophosphamide 500mg D1-8-15 + thalidomide 100-200mg D1-28 + dexamethasone 40mg/week (28 days cycle)- 4 cycles. ) + Daratumumab 16mg/Kg every week on cycles 1 and 2 and every other week at cycles 3 and 4- (total of 12 doses). Then Daratumumab 16mg/Kg after D+30, every other week as pre consolidation until starts full consolidation D+90-120 every other week (total of 4 doses) + thal100mg D1-28 during sixteen weeks as full consolidation. Follow by Daratumumab 16mg/Kg once a month as maintenance until progression or limiting adverse event (total of 28 planning doses). Total scheme Daratumumab doses= 50 doses = PROTOCOL MAXDARA.

Combination Product: Cyclo Thal Dex Daratumumab

Interventions

Cyclo Thal Dex Daratumumab COMBINATION_PRODUCT

Cyclo Thal Dex Daratumumab

Also known as: CTD-Dara,

Cyclo Thal Dex Daratumumab

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
• Women of childbearing potential must commit to either abstain continuously from sexual intercourse or to use 2 methods of reliable birth control simultaneously as deemed appropriate by the Investigator. Contraception must begin 4 weeks prior to dosing and must continue for 4 months after the last dose of DARATUMUMAB
• Man, who is sexually active with a woman of child-bearing potential potential must agree to use a latex or synthetic condom, even if he had a successful vasectomy, must agree to use an adequate contraception method as deemed appropriate by the Investigator, and must also agree to not donate sperm during the study and for four weeks after last dose of thalidomide and DARATUMUMB
• Participants with known or suspected COPD or asthma must have a FEV1 test during Screening

You may not qualify if:

• Participant has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance (presence of serum M-protein \<3 g/dL; absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the M-protein), or smoldering multiple myeloma (asymptomatic multiple myeloma with absence of related organ or tissue impairment end organ damage, and absence of biomarkers activity)
• Participant has a diagnosis of Waldenström's disease, or other conditions in which IgM M protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions
• Participant has a history of malignancy (other than multiple myeloma) within 5 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the Investigator, with concurrence with the medical monitor, is considered cured with minimal risk of recurrence within 5 years)
• Participant has prior or current systemic therapy or SCT for multiple myeloma, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for a maximum 4 days) of corticosteroids 30 days before treatment
• Participant has had radiation therapy within 14 days of randomization
• Participant has known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume in 1 second \[FEV1\] \<50% of predicted normal), persistent asthma, or a history of asthma within the last 2 years (controlled intermittent asthma or controlled mild persistent asthma is allowed)
• Participants with heart block defined by electrocardiogram or not treated arrhythmia
• Participant is known to be seropositive for history of human immunodeficiency virus (HIV) or known to have active hepatitis B or hepatitis C or Chagas disease positivity with cardiac involvement
• Patient has malignancy , 3 years of first dose of study treatment (except basal or squamous cell carcinoma or in situ cancer of the cervix)
• Patients has not recovered from all therapy-related toxicities , grade 2 CTCAE; patients has undergone major surgery \< 2 weeks prior to starting drug
• All patients must agree to follow the regional requirements for Thalidomide counseling, pregnancy testing and birth control. For women of childbearing potential (WOCBP) this includes pregnancy testing prior to prescribing thalidomide and to either commit to continued abstinence from heterosexual intercourse or begin acceptable methods of birth control for 28 days prior to prescribing thalidomide, during therapy and for 28 days after the last dose of thalidomide. WOCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a WOCBP even if they have had a successful vasectomy and must agree not to donate semen during study drug therapy and for a period of time after therapy. All patients must abstain from donating blood, agree not to share thalidomide with others and be counseled about the risks of thalidomide

Sponsors & Collaborators

• Grupo de Estudos Multicentricos em Onco-Hematologia: lead

Study Sites (1)

CEHON - Centro de Hematologia e Oncologia da Bahia

Salvador, Estado de Bahia, 40110150, Brazil

RECRUITING

Related Publications (12)

• Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011 Mar 17;364(11):1046-60. doi: 10.1056/NEJMra1011442. No abstract available.

  PMID: 21410373 RESULT

• Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, Kumar S, Hillengass J, Kastritis E, Richardson P, Landgren O, Paiva B, Dispenzieri A, Weiss B, LeLeu X, Zweegman S, Lonial S, Rosinol L, Zamagni E, Jagannath S, Sezer O, Kristinsson SY, Caers J, Usmani SZ, Lahuerta JJ, Johnsen HE, Beksac M, Cavo M, Goldschmidt H, Terpos E, Kyle RA, Anderson KC, Durie BG, Miguel JF. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014 Nov;15(12):e538-48. doi: 10.1016/S1470-2045(14)70442-5. Epub 2014 Oct 26.

  PMID: 25439696 RESULT

• Morgan GJ, Davies FE, Gregory WM, Bell SE, Szubert AJ, Navarro Coy N, Cook G, Feyler S, Johnson PR, Rudin C, Drayson MT, Owen RG, Ross FM, Russell NH, Jackson GH, Child JA; National Cancer Research Institute Haematological Oncology Clinical Studies Group. Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results. Haematologica. 2012 Mar;97(3):442-50. doi: 10.3324/haematol.2011.043372. Epub 2011 Nov 4.

  PMID: 22058209 RESULT

• Sondergeld P, van de Donk NW, Richardson PG, Plesner T. Monoclonal antibodies in myeloma. Clin Adv Hematol Oncol. 2015 Sep;13(9):599-609.

  PMID: 26452191 RESULT

• Deaglio S, Mehta K, Malavasi F. Human CD38: a (r)evolutionary story of enzymes and receptors. Leuk Res. 2001 Jan;25(1):1-12. doi: 10.1016/s0145-2126(00)00093-x.

  PMID: 11137554 RESULT

• Reinherz EL, Kung PC, Goldstein G, Levey RH, Schlossman SF. Discrete stages of human intrathymic differentiation: analysis of normal thymocytes and leukemic lymphoblasts of T-cell lineage. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1588-92. doi: 10.1073/pnas.77.3.1588.

  PMID: 6966400 RESULT

• Verfaillie CM, Miller JS. CD34+/CD33- cells reselected from macrophage inflammatory protein 1 alpha+interleukin-3--supplemented "stroma-noncontact" cultures are highly enriched for long-term bone marrow culture initiating cells. Blood. 1994 Sep 1;84(5):1442-9.

  PMID: 7520771 RESULT

• Phipps C, Chen Y, Gopalakrishnan S, Tan D. Daratumumab and its potential in the treatment of multiple myeloma: overview of the preclinical and clinical development. Ther Adv Hematol. 2015 Jun;6(3):120-7. doi: 10.1177/2040620715572295.

  PMID: 26137203 RESULT

• Laubach JP, Richardson PG. CD38-Targeted Immunochemotherapy in Refractory Multiple Myeloma: A New Horizon. Clin Cancer Res. 2015 Jun 15;21(12):2660-2. doi: 10.1158/1078-0432.CCR-14-3190. Epub 2015 Apr 15.

  PMID: 25878332 RESULT

• van de Donk NW, Lokhorst HM. New developments in the management and treatment of newly diagnosed and relapsed/refractory multiple myeloma patients. Expert Opin Pharmacother. 2013 Aug;14(12):1569-73. doi: 10.1517/14656566.2013.805746. Epub 2013 May 31.

  PMID: 23721099 RESULT

• Lonial S, Weiss BM, Usmani SZ, Singhal S, Chari A, Bahlis NJ, Belch A, Krishnan A, Vescio RA, Mateos MV, Mazumder A, Orlowski RZ, Sutherland HJ, Blade J, Scott EC, Oriol A, Berdeja J, Gharibo M, Stevens DA, LeBlanc R, Sebag M, Callander N, Jakubowiak A, White D, de la Rubia J, Richardson PG, Lisby S, Feng H, Uhlar CM, Khan I, Ahmadi T, Voorhees PM. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. Lancet. 2016 Apr 9;387(10027):1551-1560. doi: 10.1016/S0140-6736(15)01120-4. Epub 2016 Jan 7.

  PMID: 26778538 RESULT

• de Queiroz Crusoe E, Leal Ribeiro Dos Santos JS, de Andrade Santos J, de Melo Santos HH, de Souza Santos A, Lucas LF, Requiao de Pinna CA, Caldas Freire PN, Araujo de Jesus A, de Moura Almeida A, Dutra DD, Chaves MF, Nicanor JS, Salvino MA, Bomfim Arruda MDG, Hungria V; GBRAM. Phase 2 trial of daratumumab, cyclophosphamide, thalidomide, and dexamethasone in newly diagnosed multiple myeloma. Blood Neoplasia. 2025 Mar 3;2(3):100081. doi: 10.1016/j.bneo.2025.100081. eCollection 2025 Aug.

  PMID: 40575076 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Juliana Santos

  CEHON

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Edvan Q Crusoé

CONTACT

+55 71 981065839; edvancrusoe@gmail.com

Débora Sacramento

CONTACT

+55 71 34963728; debora.sanntos@clinicacehon.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Gammopathy outpatient cordinator

Study Record Dates

• First Submitted: November 19, 2018
• First Posted: January 3, 2019
• Study Start: November 20, 2018
• Primary Completion: May 1, 2020
• Study Completion: April 1, 2022
• Last Updated: January 3, 2019

Record last verified: 2019-01

Locations

BR (1)