Multiple MyelomaPhase 2IFM2016-03NCT03393273
Elotuzumab in Patients With Multiple Myeloma Before and After Peripheral Stem Cell Autologous Graft
A Phase 2 study testing Elotuzumab in people with Multiple Myeloma, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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 Read more about this study
- Who is it for?
- Ages 66 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Elotuzumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteFrance
- Study dates
- 20 Feb 2018to 15 Jan 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 66 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
France1 site
Hématologie et thérapie cellulaire, Hôpital Saint Antoine
Paris, 75012
About this study
Official title: Induction and Consolidation With Elotuzumab Before and After Peripheral Stem Cell Autologous Graft in Elderly Patients With Multiple Myeloma
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
Read the 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.
- Conditions
- Multiple Myeloma
- Being tested
- Elotuzumab
- Keywords
- Stem Cell autologous graft, Elotuzumab, Multiple myeloma, Elderly
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ElotuzumabDrug
Also called Empliciti®
- 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
| Study group | Role | What they receive |
|---|---|---|
| Elotuzumab | Experimental | 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. Receives: Drug: Elotuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximal response rate Assesment of the International Myeloma Working Group uniform response criteria
Assesment of the International Myeloma Working Group uniform response criteria
Measured: 1 month after the last consolidation cure
Secondary outcomes (6)
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).
Measured: one year after the last consolidation cure
evaluation of the answer to the treatment to improve or maintain the response
Best response obtained or maintained for each therapeutical phase
Measured: 12 month of treatment from inclusion
Role of the consolidation phase in the improvement or maintenance of the response to the treatment Time before progression
Time before progression
Measured: From inclusion to month 36
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
Measured: from inclusion to month 36
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
Measured: From inclusion to the end of the 12 treatment-month
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)
Measured: From inclusion to month 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2018
- Study start20 Feb 2018
- Primary completion15 Jan 2019
- Study completion15 Jan 2019
Why it stopped: Investigator decision in accordance with the promotor
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mohamad Mohty, PU-PH, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03393273
- Sponsor's protocol ID
- P170103
- Other IDs
- 2017-001446-10, 2017
- Acronym
- IFM2016-03
- Status last verified
- Jul 2019
- First submitted
- 7 Dec 2017
- Last updated
- 17 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Induction and Consolidation With Elotuzumab Before and After Peripheral Stem Cell Autologous Graft in Elderly Patients With Multiple Myeloma
- ClinicalTrials.gov ID
- NCT03393273
- Acronym / sponsor ID
- IFM2016-03 / P170103
- Conditions
- Multiple Myeloma
- Keywords
- Stem Cell autologous graft, Elotuzumab, Multiple myeloma, Elderly
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Investigator decision in accordance with the promotor
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 20 Feb 2018 (actual)
- Primary completion
- 15 Jan 2019 (actual)
- Study completion
- 15 Jan 2019 (actual)
- First posted
- 8 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Elotuzumab | Experimental | Drug: ElotuzumabThis 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. |
Who may qualify
- Ages
- 66 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (15 listed)
- 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,
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ElotuzumabAlso: Empliciti®* 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 | Drug | Elotuzumab |
Primary outcome
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
6 secondary outcomes
survival and progression-free survival
Time frame: one year after the last consolidation cure
evaluation of the answer to the treatment to improve or maintain the response
Time frame: 12 month of treatment from inclusion
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
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
correlation between residual disease and duration of the response to the treatment
Time frame: From inclusion to the end of the 12 treatment-month
Tolerance to each phase of treatment (the induction phase, the intensive treatment, the consolidation phase)
Time frame: From inclusion to month 36
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2019.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mohamad Mohty, PU-PH principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Elotuzumab in people with Multiple Myeloma, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 17 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximal response rate Assesment of the International Myeloma Working Group uniform response criteria (time frame: 1 month after the last consolidation cure). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2019.