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

Primary Purpose

Multiple Myeloma

Status

Withdrawn

Phase

Phase 2

Locations

France

Study Type

Interventional

Intervention

Elotuzumab

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Stem Cell autologous graft, Elotuzumab, Multiple myeloma, Elderly

Eligibility Criteria

66 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Hématologie et thérapie cellulaire, Hôpital Saint Antoine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Elotuzumab

Arm Description

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.

Outcomes

Primary Outcome Measures

Maximal response rate Assesment of the International Myeloma Working Group uniform response criteria

Assesment of the International Myeloma Working Group uniform response criteria

Secondary Outcome Measures

survival and progression-free survival

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).

evaluation of the answer to the treatment to improve or maintain the response

Best response obtained or maintained for each therapeutical phase

Role of the consolidation phase in the improvement or maintenance of the response to the treatment Time before progression

Time before progression

Conversion from negative residual disease to positive residual disease or maintenance of a negative residual disease during all therapeutical phases

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

correlation between residual disease and duration of the response to the treatment

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

Tolerance to each phase of treatment (the induction phase, the intensive treatment, the consolidation phase)

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)

Full Information

NCT ID

NCT03393273

First Posted

December 7, 2017

Last Updated

July 15, 2019

Sponsor

Assistance Publique - Hôpitaux de Paris

1. Study Identification

Unique Protocol Identification Number

NCT03393273

Brief Title

Elotuzumab in Patients With Multiple Myeloma Before and After Peripheral Stem Cell Autologous Graft

Acronym

IFM2016-03

Official Title

Induction and Consolidation With Elotuzumab Before and After Peripheral Stem Cell Autologous Graft in Elderly Patients With Multiple Myeloma

Study Type

Interventional

2. Study Status

Record Verification Date

July 2019

Overall Recruitment Status

Withdrawn

Why Stopped

Investigator decision in accordance with the promotor

Study Start Date

February 20, 2018 (Actual)

Primary Completion Date

January 15, 2019 (Actual)

Study Completion Date

January 15, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assistance Publique - Hôpitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Myeloma

Keywords

Stem Cell autologous graft, Elotuzumab, Multiple myeloma, Elderly

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Elotuzumab

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Elotuzumab

Other Intervention Name(s)

Empliciti®

Intervention Description

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

Primary Outcome Measure Information:

Title

Maximal response rate Assesment of the International Myeloma Working Group uniform response criteria

Description

Assesment of the International Myeloma Working Group uniform response criteria

Time Frame

1 month after the last consolidation cure

Secondary Outcome Measure Information:

Title

survival and progression-free survival

Description

Time Frame

one year after the last consolidation cure

Title

evaluation of the answer to the treatment to improve or maintain the response

Description

Best response obtained or maintained for each therapeutical phase

Time Frame

12 month of treatment from inclusion

Title

Role of the consolidation phase in the improvement or maintenance of the response to the treatment Time before progression

Description

Time before progression

Time Frame

From inclusion to month 36

Title

Conversion from negative residual disease to positive residual disease or maintenance of a negative residual disease during all therapeutical phases

Description

Time Frame

from inclusion to month 36

Title

correlation between residual disease and duration of the response to the treatment

Description

Time Frame

From inclusion to the end of the 12 treatment-month

Title

Tolerance to each phase of treatment (the induction phase, the intensive treatment, the consolidation phase)

Description

Time Frame

From inclusion to month 36

10. Eligibility

Sex

All

Minimum Age & Unit of Time

66 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mohamad Mohty, PU-PH

Organizational Affiliation

Assistance Publique - Hôpitaux de Paris

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hématologie et thérapie cellulaire, Hôpital Saint Antoine

City

Paris

ZIP/Postal Code

75012

Country

France

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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Elotuzumab in Patients With Multiple Myeloma Before and After Peripheral Stem Cell Autologous Graft

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