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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03792620
Recruitment Status : Recruiting
First Posted : January 3, 2019
Last Update Posted : January 3, 2019
Information provided by (Responsible Party):
Edvan de Queiroz Crusoe, Grupo de Estudos Multicentricos em Onco-Hematologia

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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Stage I Combination Product: Cyclo Thal Dex Daratumumab Phase 3

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Conceptual Study of Daratumumab Intensified Treatment to Eligible Multiple Myeloma New Patients- Cyclophosphamide, Thalidomide, Dexamethasone and Daratumumab Induction, Follow by Daratumumab Consolidation and Maintenance
Actual Study Start Date : November 20, 2018
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : April 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Cyclo Thal Dex Daratumumab

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
Cyclo Thal Dex Daratumumab
Other Name: CTD-Dara,

Primary Outcome Measures :
  1. Incidence of response rate better than very good partial response after ASCT [ Time Frame: 8 months after starting treatment ]
    Number of patients that obtained better than VGPR after ASCT based on the IMWG description

Secondary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v 4.0 [ Time Frame: 24 months ]
    Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0

  2. Incidence of Overall response rate [ Time Frame: 24 months ]
    Evaluate response rate as defined by the International Myeloma Working Group) IMWG- Minimal residual Disease (MRD), stringent complete Response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), and minimal response (MR) in patients treated with this protocol.

  3. Duration of response after Dara-CTD treatment [ Time Frame: 24 months ]
    Evaluate duration of response in patients treated with Daratumumab Cyclophosphamide thalidomide and dexamethasone treatment

  4. Time of response after Dara-CTD treatment [ Time Frame: 24 months ]
    Evaluate the specific moment of time of partial response observed after Daratumumab Cyclophosphamide thalidomide and dexamethasone treatment

  5. Incidence of Minimal residual disease evaluate by PET CT image [ Time Frame: 24 months ]
    Number of bone and extra bone marrow disease observed by PET CT image at diagnosis and after consolidation therapy by International Myeloma Working Group recommendations

  6. Time to bone marrow engraftment [ Time Frame: 24 months ]
    Measurement of neutrophil number in peripheral blood sample to evaluate the time of bone marrow engraftment

  7. Number of progenitor cell collected after condition treatment [ Time Frame: 24 months ]
    Flow cytometry of progenitor cell number collected

  8. Time to Disease Progression (TTP). [ Time Frame: 24 months ]
    Time to Disease Progression (TTP). The TTP is defined as time from date of randomization to date of first documented evidence of PD, as defined by IMWG criteria

  9. Progression-Free Survival (PFS) and PFS on Next Line of Therapy (PFS2). [ Time Frame: 24 months ]
    Progression-Free Survival (PFS) and PFS on Next Line of Therapy (PFS2).The PFS2 is defined as time from randomization to progression on next line of treatment or death, whichever occur first. Disease progression will be based on IMWG guide

  10. Percentage of Participants With Negative Minimal Residual Disease (MRD). [ Time Frame: 24 months ]
    The MRD assessment will be done by flow cytometry in bone marrow aspirate and in stem cell collected pack of participants four pre specified times- after induction, after ASCT, after consolidation and 1 year of maintenance

  11. Peripheral blood lymphocytes number [ Time Frame: 24 months ]
    Peripheral blood lymphocytes analysis will be done by Flow cytometry in spite of look at T and B population. The analysis will be performing at the same time as MRD

  12. Time To Next treatment. [ Time Frame: 24 months ]
    Time To Next treatment. Time to next treatment is defined as the time from randomization to the start of next-line treatment.

  13. Duration of Response (DR). [ Time Frame: 24 months ]
    Duration of Response (DR). The DR is time from date of initial documentation of response (PR or better) to date of first documented PD, as defined by IMWG criteria

  14. Overall Survival (OS). [ Time Frame: 24 months ]
    Overall Survival (OS). The OS is the time from date of randomization to date of participant's death or follow- up lost

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
  • Participants who are newly diagnosed considered for high-dose chemotherapy due to: being age <=65 years; without presence of important comorbidity condition(s) likely to have a negative impact on tolerability of high dose chemotherapy with stem cell transplantation. Committee review and approval of participants is required before inclusion
  • 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

Exclusion Criteria:

  • 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

Key exclusion criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03792620

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Contact: Edvan Q Crusoé +55 71 981065839
Contact: Débora Sacramento +55 71 34963728

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CEHON - Centro de Hematologia e Oncologia da Bahia Recruiting
Salvador, Bahia, Brazil, 40110150
Contact: Edvan Q Crusoé    +55 71 981065839   
Contact: Débora Sacramento    +55 71 34963725      
Principal Investigator: Edvan Q Crusoe         
Sponsors and Collaborators
Grupo de Estudos Multicentricos em Onco-Hematologia
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Principal Investigator: Juliana Santos CEHON

Publications of Results:

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Responsible Party: Edvan de Queiroz Crusoe, Gammopathy outpatient cordinator, Grupo de Estudos Multicentricos em Onco-Hematologia Identifier: NCT03792620     History of Changes
Other Study ID Numbers: U1111-1219-9010
CAAE ( Other Identifier: 96591818.0.0000.0048 )
First Posted: January 3, 2019    Key Record Dates
Last Update Posted: January 3, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Edvan de Queiroz Crusoe, Grupo de Estudos Multicentricos em Onco-Hematologia:
multiple myeloma
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Monoclonal
Physiological Effects of Drugs
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antiparasitic Agents