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Elotuzumab in Patients With Multiple Myeloma Before and After Peripheral Stem Cell Autologous Graft (IFM2016-03)

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ClinicalTrials.gov Identifier: NCT03393273
Recruitment Status : Not yet recruiting
First Posted : January 8, 2018
Last Update Posted : May 15, 2018
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:
This is a multicenter, open-label phase II study, assessing the efficacy of elotuzumab in elderly patients with multiple myeloma undergoing peripheral stem cell autologous graft

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

Detailed Description:

In patients of 65 years of age or older, intensive treatment (TI) with hematopoietic stem cell autologous graft (ASCH) is not considered as the gold standard. Nowadays, given the rise of new treatments, new studies assessing TI with ASCH in elderly, seem required. The association bortezomib (VEL) - thalidomide (THAL) - dexamethasone (DEX) is considered as the standard induction (Kumar, Flinn et al. 2012, Ludwig, Viterbo et al. 2013). However, more and more strategies with immunotherapies are developed. Furthermore, it looks encouraging to use several monoclonal antibodies at different clinical development levels. Thus, elotuzumab (ELO) is an IgG1 (immunoglobulin gamma-1) (IgGκ) humanized monoclonal antibody directed against SLAMF7. SLAMF7 is a glycoprotein expressed by myeloma cells and natural killer (NK) but not by healthy tissues. Consequently, elotuzumab can kill specifically myeloma cells without affecting healthy tissues (Hsi, Steinle et al. 2008). A phase I study assessed the safety of ELO in association with VEL, REV (Lenalidomide) and DEX in induction first-line treatment in elderly patients with median age of 67 years (Usmani, Sexton et al. 2015). There were no significant increase of side effects with this association compared with side effects usually reported with VEL, REV and DEX. Thus, adding ELO could lead to an increase of response rate, with no increase of toxicity.

For more than 10 years, the standard intensive treatment associates a MEL (MELPHALAN) conditioning (200 mg/m2) with a blood graft. In a recent study, almost all patients aged between 65-69 and 70-74 years received MEL at 200 mg/m2. The adverse events rate was similar between the different ages and a very low non-tied relapse mortality. Thus, in elderly patients selected, the use of MEL at 200 mg/m2 seems sure.

Moreover, it's widely admitted that the conditioning treatment should be based on an efficient drugs association with a limited toxicity. Studies assessing consolidation treatment with an association of new drugs are limited. Initial results suggest that the use of new drugs after intensive treatment (IT) with ASCH should increase response rate and improve progression-free survival and global survival.

The aim of this study IFM 2016-03 is to assess intensive treatment (IT) with AHSCT (Autologous hematopoietic stem cell transplantation) in elderly and to associate the different steps (induction, high dose conditioning, consolidation) with immunotherapy. Given the prior results of IFM and international studies, a VGPR (Very Good Partial Response) rate of around 85% is expected.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Induction and Consolidation With Elotuzumab Before and After Peripheral Stem Cell Autologous Graft in Elderly Patients With Multiple Myeloma
Estimated Study Start Date : May 2018
Estimated Primary Completion Date : May 2023
Estimated Study Completion Date : May 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma
Drug Information available for: Elotuzumab

Arm Intervention/treatment
Experimental: Elotuzumab
This is a single arm phase II trial to assess the Very Good Partial Response rate of a strategy involving autologous hematopoietic stem cell transplantation, after intensive treatment and followed by consolidation phase, with elotuzumab, dexamethasone, velcade, and thalidomide in elderly patients.
Drug: Elotuzumab
  • Induction 4 cycles of 28 days Elotuzumab IV, 10 mg/Kg, D1, 8, 15, 22 Dexamethasone PO, 40 mg/d, D1, 8, 15 Velcade® IV, 1,3 mg/m2/d, D1, 4, 8, 11 Thalidomide PO, 100 mg/d, D1 to 21
  • melphalan 140-200 mg/m2 one day followed by autologous hematopoietic stem cell transplantation
  • Consolidation 2 cycles of 28 days (2 to 3 months after autograft) Elotuzumab IV, 10 mg/Kg, D1, 8, 15 and 22 Dexamethasone PO, 40 mg/d, D1, 8 and 15 Velcade® IV, 1,3 mg/m2/d, D1, 4, 8, and 11 Thalidomide® PO, 100 mg/d, D1 to 21
Other Name: Empliciti®




Primary Outcome Measures :
  1. Maximal response rate Assesment of the International Myeloma Working Group uniform response criteria [ Time Frame: 1 month after the last consolidation cure ]
    Assesment of the International Myeloma Working Group uniform response criteria


Secondary Outcome Measures :
  1. survival and progression-free survival [ Time Frame: one year after the last consolidation cure ]

    Survival rate and global follow-up

    • Progression-free survival is defined as the duration between the beginning of treatment to the occurrence of a disease progression or death (whichever is the cause), according event occurring first.
    • Survival rate and global follow-up is defined as the duration between the start of treatment to death (whatever the cause).

  2. evaluation of the answer to the treatment to improve or maintain the response [ Time Frame: 12 month of treatment from inclusion ]
    Best response obtained or maintained for each therapeutical phase

  3. Role of the consolidation phase in the improvement or maintenance of the response to the treatment Time before progression [ Time Frame: From inclusion to month 36 ]
    Time before progression

  4. Conversion from negative residual disease to positive residual disease or maintenance of a negative residual disease during all therapeutical phases [ Time Frame: from inclusion to month 36 ]
    Conversion rate from negative residual disease to positive residual disease or maintenance of a negative residual disease during induction,intensive treatment (IT) with AHSC (autograft of hematopoietic stem cells) and consolidation

  5. correlation between residual disease and duration of the response to the treatment [ Time Frame: From inclusion to the end of the 12 treatment-month ]
    Comparison of response duration, overall survival and event-free survival between patients with negative residual disease and the other patients, after the induction phase and at the end of the treatment phase

  6. Tolerance to each phase of treatment (the induction phase, the intensive treatment, the consolidation phase) [ Time Frame: From inclusion to month 36 ]

    Tolerance to each therapeutical phase will be assessed with:

    • ECOG (Eastern Cooperative Oncology Group) performance status
    • Adverse events rate, serious adverse events rate
    • Biological parameters (blood count and biochemistry)



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Ages Eligible for Study:   66 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Multiple myeloma de novo.
  • Stage DS (Durie-Salmon) : III, II, I with at least 1 symptomatic bone lesion (confirmed by radiology).
  • Age > 65 years
  • Indication for a first line treatment with induction, stem cell autologous graft and consolidation
  • Available documentation including cytogenetic and International Staging System (ISS) of the initial diagnosis before inclusion,
  • Effective contraceptive method for men with a partner of childbearing age during all the treatment period and within 6 months after the last cure
  • Affiliated to social security
  • Written informed consent
  • Willingness and ability to respect the visits and all the demands required by the study
  • Patient eligible to a high dose chemotherapy and fulfilling the following biological criteria :

    • Neutrophils ≥ 1,0 × 109/L
    • Platelets ≥ 75 ×109/L (platelets transfusions are not allowed within 3 days before inclusion)
    • Total bilirubin ≤ 1,5 × upper limit.
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × upper limit
    • Creatinin clearance > 50 mL/min

Exclusion Criteria:

  • Diagnosis and treatment for any other cancer within five years before inclusion or any diagnosis for any cancer. Patients with a skin cancer (except melanoma or carcinoma in situ) are not excluded in case of complete resection.
  • Central nervous system disease
  • Infection requiring an intravenous (IV) antibiotherapy or any severe infection within 14 days before inclusion
  • Diagnosis of any of the following diseases : Waldenström disease, POEMS (polyneuropathy, endocrinopathy, organomegaly, monoclonal gammapathy and skin lesions), plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome or myeloproliferative disorder.
  • Uncontrolled cardiopathy including : uncontrolled hypertension, uncontrolled heart arrhythmia, nonsymptomatic congestive cardiac failure, unstable angina or myocardial infarction within 6 months before inclusion
  • Active infection with hepatitis B or C virus ; positive HIV serology
  • Any comorbidity or severe concomitant disease incompatible with the patient inclusion or interfering with the safety assessment of the study treatments.
  • Psychiatric history or any social condition limiting the patient compliance.
  • Documented allergy to any studied treatment or any of their components.
  • Disability to take oral treatments, inability or refusal to adhere to treatment constraints, or any digestive surgery interfering with oral absorption or treatment tolerance.
  • Any experimental treatment within 30 days prior to the administration of the first dose of the studied treatmentParticipation to another clinical trial
  • Prior participation to a clinical trial with elotuzumab, no matter the arm of treatment.
  • Administration of any pharmaceutical speciality acting against myeloma - such as systemic corticosteroids (>10 mg of prednisone equivalent a day) or clarithromycin - within the month prior to the inclusion. In case of emergency, patients can receive dexamethasone (40mg/day, 4 consecutive days, maximum dose of 160mg) between screening and randomization

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 ClinicalTrials.gov identifier (NCT number): NCT03393273


Contacts
Contact: Mohamad Mohty, PU-PH 01.49.28.26.20 mohamad.mohty@inserm.fr
Contact: Florent Malard, CCU-AH 01.49.28.26.20 malardf@yahoo.fr

Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Mohamad Mohty, PU-PH Assistance Publique - Hôpitaux de Paris

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03393273     History of Changes
Other Study ID Numbers: P170103
2017-001446-10 ( EudraCT Number )
First Posted: January 8, 2018    Key Record Dates
Last Update Posted: May 15, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Stem Cell autologous graft
Elotuzumab
Multiple myeloma
Elderly

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Thalidomide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents