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Multiple MyelomaPhase 2IFM 2018-04NCT03606577

An Intensive Program With Quadruplet Induction and Consolidation Plus Tandem Autologous Stem Cell Transplantation in Newly Diagnosed High Risk Multiple Myeloma Patients

A Phase 2 study testing Carfilzomib, Daratumumab and Lenalidomide in people with Multiple Myeloma, run by Nantes University Hospital at 12 sites in France.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

According to international guidelines, upfront therapy for transplant eligible myeloma patients should include triplet induction containing proteasome inhibitor and immunomodulatory agent, autologous stem cell transplant, PI+Imid based triplet consolidation and lenalidomide maintenance. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Multiple Myeloma
What is being tested?
Carfilzomib, Daratumumab and Lenalidomide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
12 sitesFrance
Study dates
30 Jul 2019to 8 Nov 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female subjects, 18 years of age or older, younger than 66 years (< 66 years)
  • Voluntary written informed consent must be given before performance of any study-related procedure not part of normal medical care, with the understanding that the subject may withdraw consent at any time without prejudice to future medical care.
  • Subject must have documented multiple myeloma satisfying the Diagnostic criteria for symptomatic Myelome Multiple and measurable disease as defined by:
  • Monoclonal plasma cells in the bone marrow ≥ 10% or presence of a biopsy proven plasmacytoma AND any one or more of the following myeloma defining events:
  • Hypercalcemia: serum calcium > 0.25 mmol/L higher than ULN or > 2.75 mmol/L
  • Renal insufficiency: creatinine clearance < 40mL/min or serum creatinine > 177 μmol/L
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  • Anemia: hemoglobin > 2 g/dL below the lower limit of normal or hemoglobin < 10 g/dL
  • Bone lesions: one or more osteolytic lesions on skeletal radiography, CT or PET-CT Or in a patient with indolent myeloma
  • Clonal bone marrow plasma cell percentage ≥ 60%
  • Involved: uninvolved serum free light chain ratio ≥ 100
  • Superior 1 focal lesion on MRI studies
  • Measurable disease as defined by the following:
  • M-component ≥ 5g/l, and/or urine M-component ≥ 200 mg/24h and/or serum Free Light Chain ≥ 100 mg/l.
  • Newly diagnosed subjects eligible for high dose therapy and autologous stem cell transplantation
  • Subject must have high risk disease according to FISH analysis: del(17p), or t(14;16) or t(4;14). The FISH-positivity cut-off value for defining the presence of del(17p) in this study is 50%
  • Karnofsky performance status score ≥ 50%
  • Women of childbearing potential must have a negative serum or urine pregnancy test within 10 to 14 days prior to therapy and repeated within 24 hours before starting study drug. They must commit to continued abstinence from heterosexual intercourse or begin 2 acceptable methods of birth control used at the same time, beginning at least 4 weeks before initiation of lenalidomide treatment and continuing for at least 30 days after the last dose of Lenalidomide. Women must also agree to notify pregnancy or doubt upon pregnancy during the study.
  • Men must agree to not father a child and agree to use a latex condom during therapy and for 4 weeks after the last dose of study drug, even if they have had a successful vasectomy, if their partner is of childbearing potential.
  • Subject must have pretreatment clinical laboratory values meeting the following criteria during the Screening Phase (Lab tests should be repeated if done more than 15 days before C1D1):
  • Hemoglobin ≥ 7.5 g/dL. Prior red blood cell transfusion or recombinant human erythropoietin use is permitted;
  • Absolute neutrophil count ≥ 1.0 Giga/l (GCSF use is permitted);
  • ASAT ≤ 3 x ULN;
  • ALAT ≤ 3 x ULN;
  • Total bilirubin ≤ 3 x ULN (except in subjects with congenital bilirubinemia, such as Gilbert syndrome, direct bilirubin ≤ 1.5 x ULN);
  • Calculated creatinine clearance ≥ 40 mL/min/1.73 m² ;
  • Corrected serum calcium ≤ 14 mg/dL; or free ionized calcium ≤6.5 mg/dL;
  • Platelet count ≥ 50 Giga/l for subjects in whom < 50% of bone marrow nucleated cells are plasma cells; otherwise platelet count > 50 Giga/l (transfusions are not permitted to achieve this minimum platelet count).
  • Affiliation with French social security system or beneficiary from such system

Who cannot join

  • Subjects must not have been treated previously with any systemic therapy for multiple myeloma. Prior treatment with corticosteroids or radiation therapy does not disqualify the subject (the maximum dose of corticosteroids should not exceed the equivalent of 160 mg of dexamethasone in a 2-week period). Two weeks must have elapsed since the date of the last radiotherapy treatment. Enrolment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 2 weeks have elapsed since the last date of therapy
  • Subject has received daratumumab or other anti-CD38 therapies previously
  • Subject has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, or solitary plasmacytoma.
  • Subject has a diagnosis of Waldenström's macroglobulinemia, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions.
  • Subject has had plasmapheresis within 28 days of C1D1.
  • Subject is exhibiting clinical signs of meningeal involvement of multiple myeloma.
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  • Myocardial infarction within 6 months prior to enrolment according to NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  • Uncontrolled hypertension
  • Subjects with known chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume (FEV1) in 1 second < 50% of predicted normal. Note that FEV1 testing is required for patients suspected of having COPD and subjects must be excluded if FEV1 < 50% of predicted normal.
  • Subjects with a history of moderate or severe persistent asthma within the past 2 years, or with uncontrolled asthma of any classification at the time of screening (Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study).
  • Subject has plasma cell leukemia (according to WHO criterion: ≥ 20% of cells in the peripheral blood with an absolute plasma cell count of more than 2 × 10^9/L) or polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes syndrome.
  • Systemic treatment with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin), strong inhibitors of CYP3A (as clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (as rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, fosphenytoin phenobarbital), or use of Ginkgo biloba or St. John's wort within 14 days before the first dose of study treatment.
  • Known intolerance to steroid therapy
  • History of hypersensitivity to any of the study medications, their analogues, or excipients in the various formulations, or to study-required co medication
  • Subject has had major surgery within 2 weeks before the first dose of study treatment or will not have fully recovered from surgery, or has surgery planned during the time the subject is expected to participate in the study. Kyphoplasty or Vertebroplasty are not considered major surgery.
  • Clinically relevant active infection or serious co-morbid medical conditions
  • Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical, breast or prostate cancer free of disease since 5 years.
  • Female subject who is pregnant or breast-feeding + male and female refusing birth control conditions
  • Serious medical or psychiatric illness likely to interfere with participation in study
  • Uncontrolled diabetes mellitus
  • Known HIV infection; Known active hepatitis B or C viral infection; or other ongoing uncontrolled infection
  • Incidence of gastrointestinal disease that may significantly after the absorption of oral drugs
  • Subjects unable or unwilling to undergo antithrombotic prophylactic treatment
  • Person under guardianship, trusteeship or deprived of freedom by a judicial or administrative decision

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

France12 sites

  • CHU Caen

    Caen

  • CHRU Dijon

    Dijon

  • CHRU - Hôpital A.Michallon

    Grenoble

  • CHD Vendée

    La Roche-sur-Yon

  • CHRU - Hôpital Claude Huriez

    Lille

  • CH de Lyon Sud

    Lyon

  • CHU de Nantes

    Nantes, Pays de la Loire Region, 44000

  • CHRU Hôpital du Haut Lévêque

    Pessac

  • CHRU - Hôpital de Pontchaillou

    Rennes

  • CHU Toulouse

    Toulouse

  • CHRU Bretonneau

    Tours

  • CHRU - Hôpitaux de Brabois

    Vandœuvre-lès-Nancy

Other trials in France

About this study

Official title: An Intensive Program With Quadruplet Induction and Consolidation Plus Tandem Autologous Stem Cell Transplantation in Newly Diagnosed High Risk Multiple Myeloma Patients: a Phase II Study of the Intergroupe Francophone du Myélome "IFM 2018-04"

According to international guidelines, upfront therapy for transplant eligible myeloma patients should include triplet induction containing proteasome inhibitor and immunomodulatory agent, autologous stem cell transplant, PI+Imid based triplet consolidation and lenalidomide maintenance. Despite this approach, virtually all MM patients experience disease relapse, especially those with High Risk disease defined by adverse cytogenetic abnormalities (i.e. del(17p), or t(14;16) or t(4;14)) detected by FISH and/or SNP arrays. Indeed, HR myeloma is associated with poorer progression free survival and overall survival and frontline therapy should therefore be improved for this subset of HR patients. The primary objective of this prospective multicenter, open label, interventional phase 2 trial is to evaluate the feasibility of an intensive program including quadruplet induction and consolidation, tandem autologous stem cell transplantation and maintenance in newly diagnosed multiple myeloma patients presenting with HR cytogenetic. Quadruplet induction and consolidation include carfilzomib, lenalidomide, dexamethasone and daratumumab. Maintenance will include lenalidomide and daratumumab. Secondary objectives will include efficacy parameters (i.e. response rate, minimal residual disease, safety, progression free survival, overall survival).

Keywords
Multiple Myeloma, Newly Diagnosed, High Risk, Revlimid, Carfilzomib, Daratumumab, Dexaméthasone
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CarfilzomibDrug

    Induction 6 cycles 20/36 mg/m² on days 1, 2, 8, 9, 15, 16 (20 mg/m² on D1 and 2 cycle 1 only) Consolidation 4 cycles Carfilzomib 20 or 36 mg/m² on days 1, 2, 8, 9, 15, 16 (20 mg/m² on D1 and 2 first cycle only)

  • DaratumumabDrug

    induction: 6 cycles Daratumumab 8/16mg/kg IV on Days 1, 8, 15, 22 for the first two cycle 2 and on days 1 and 15 for cycles 3 to 6. (8mg/kg on D1 \& D2 cycle 1 only) Consolidation: daratumumab 4 cycles 16mg/kg IV Day 1, Day 15 Maintenance Daratumumab 16mg/kg IV once every 8 weeks for 2 years (or until documented disease progression)

  • LenalidomideDrug

    induction: 6 cycles Lenalidomide 25 mg/day from day 1 to day 21 Consolidation: 4 cycles 15 mg/day from Day 1 to Day 21 (first cycle ) 25 mg/day from Day 1 to Day 21 (in the following cycle) Maintenance therapy 10mg/day, Day 1 to 21, for 2 years (or until documented disease progression)

  • DexamethasoneDrug

    induction 6 cycles 20 mg/day on days 1-2, 8-9, 15-16 and 22-23 Consolidation 4 cycles 40 mg/Day on Days 1, 8, 15 and 22

Study groups in NCT03606577
Study groupRoleWhat they receive
Carfilzomib, Daratumumab, Lenalidomide and DexaméthasoneExperimentalNot described
Receives: Drug: Carfilzomib; Drug: Daratumumab; Drug: Lenalidomide; Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of patients receiving the second Autologous Stem Cell Transplant

    Measured: 15 months

Secondary outcomes (9)

  1. Number of adverse events

    Measured: 48 months

  2. Number of responses

    Measured: 48 months

  3. Number of MRD

    Measured: 48 months

  4. Number of death

    Measured: 84 months

  5. Percentage of time to progression

    Measured: 84 months

  6. Number of patients having survival without progress

    Measured: 84 months

  7. Percentage duration of response

    Measured: 84 months

  8. Number of cells collected

    Measured: 168 days

  9. percentage of value of biological prognostic factors

    Measured: 48 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jul 2018
  2. Study start30 Jul 2019
  3. Primary completion8 Feb 2022 (estimated)
  4. Study completion8 Nov 2027 (estimated)

Resources

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
Model description
One group of subjects who must have documented Multiple Myeloma High Risk satisfying the CRAB and measurable disease.
Masking
None (open label)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03606577
Sponsor's protocol ID
RC18_0206
Acronym
IFM 2018-04
Status last verified
Jul 2020
First submitted
20 Jul 2018
Last updated
28 Apr 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Touzeau C, Perrot A, Hulin C, Manier S, Macro M, Chretien ML, Karlin L, Escoffre M, Jacquet C, Tiab M, Leleu X, Avet-Loiseau H, Jobert A, Planche L, Corre J, Moreau P. Daratumumab, carfilzomib, lenalidomide, and dexamethasone with tandem transplant for high-risk newly diagnosed myeloma. Blood. 2024 May 16;143(20):2029-2036. doi: 10.1182/blood.2023023597.

    PubMed 38394666

  • Pawlyn C. High-risk myeloma: a challenge to define and to determine the optimal treatment. Lancet Haematol. 2021 Jan;8(1):e4-e6. doi: 10.1016/S2352-3026(20)30361-6. Epub 2020 Dec 22. No abstract available.

    PubMed 33357481

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Carfilzomib, Daratumumab and Lenalidomide in people with Multiple Myeloma, run by Nantes University Hospital at 12 sites 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 28 inclusion and 24 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: under way, not looking for participants, as of the sponsor's last update on 28 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites 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?

This study is still under way. Results are not available in the source record yet.

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?

Percentage of patients receiving the second Autologous Stem Cell Transplant (time frame: 15 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03606577, which also lists 2 linked publications.

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 28 Apr 2021.

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