Iberdomide as maintenance therapy after autologous stem cell transplantation in newly diagnosed multiple myeloma patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

European Myeloma Network B.V., Emn Trial Office S.r.l. Impresa Sociale

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

22 Feb 2021 → ongoing

Decision date (initial)

2024-10-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Celgene International II SARL

External identifiers

EU CT number

2024-512354-21-00

EudraCT number

2020-003091-40

ClinicalTrials.gov

NCT04564703

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Therapy

To evaluate the efficacy (rate of improvement in response from PR to ≥VGPR; from VGPR to ≥CR; from CR to sCR) of three different dose levels of Iberdomide in maintenance treatment after ASCT

Secondary objectives 9

1. Rate of next-generation flow (NGF) minimal residual disease (MRD) conversion from positive to negative
2. Rate of adverse events
3. Safety and efficacy in different subset of participant with different prognostic features
4. Time to Progression (TTP)
5. Progression Free Survival (PFS)
6. Time to next therapy (TNT)
7. Progression Free Survival 2 (PFS2)
8. Overall survival (OS)
9. To evaluate the pharmacokinetics (PK) of iberdomide in participants with NDMM

Conditions and MedDRA coding

Newly diagnosed multiple myeloma

Study design 3 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. Participants with newly diagnosed MM, requiring therapy due to the presence of CRAB symptoms or myeloma defining events and measurable disease (sPEP ≥0.5 g/dL and/or uPEP ≥ 200 mg/24h and/or FLC involved ≥ 10 mg/dL with abnormal FLC ratio) before induction therapy with a PI and IMID-containing regimen
2. Participants with complete baseline evaluation at the time of diagnosis according to revised International Staging System (R-ISS) (cytogenetic profile, ISS and LDH)
3. Participants treated with proteasome inhibitor plus immunomodulatory drug-based induction (3-6 cycles), followed by single or double autologous stem cell transplant (ASCT) with melphalan as condItioning regimen +/- consolidation.
4. Participants within 15 months from diagnosis and 120 days after last ASCT or consolidation treatment, if performed, who achieved at least a partial response (PR), according to IMWG criteria
5. Participants willing and able to follow the trial procedures
6. Participants must understand and voluntary sign an ICF prior to any study related assessment/procedurs being conducted
7. Age ≥18 years
8. ECOG performance status 0-1
9. A female of childbearing potential (FCBP) is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) and must: - Have two negative pregnancy tests as verified by the Investigator prior to starting trial treatment. She must agree to ongoing pregnancy testing during the course of the trial, and after end of trial treatment. This applies even if the participant practices true abstinence* from heterosexual contact. - Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with two forms of contraception: one highly effective, and one additional effective (barrier) measure of contraception without interruption 28 days prior to starting investigational product, during the trial treatment (including dose interruptions), and for at least 28 days after the last dose of CC-220.
10. Male participants must: Practice true abstinence* (which must be reviewed on a monthly basis and source documented) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the trial, during dose interruptions and for at least 90 days following the last dose of trial treatment, even if he has undergone a successful vasectomy. *True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the participant. [Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.]
11. Males must agree to refrain from donating sperm while on trial treatment, during dose interruptions and for at least 90 days following last dose of trial treatment.
12. All participants must agree to refrain from donating blood while on study treatment, during dose interruptions and for at least 28 days following the last dose of trial treatment.
13. All male and female participants must follow all requirements defined in the Pregnancy Prevention Program (v5.1).
14. Participant agree to refrain from donating blood while on iberdomide, during dose interruption and for at least 28 days following the last iberdomide dose
15. Baseline values: - ANC ≥1.0 x 10^9/L without use of growth factors; - PLTs≥75 x10^9/L (transfusions within 14 days from Day1 cycle 1 to achieve this cut off are not allowed); - Hb >8 g/dL (transfusions within 14 days from Day1 cycle 1 to achieve this cut off are not allowed);
16. Life expectancy ≥ 3 months

Exclusion criteria 16

1. Systemic AL amyloidosis or plasma cell leukemia (>2.0x109/L circulating plasma cells by standard differential) or Waldenstrom’s macroglobulinemia
2. Participant has known meningeal involvement of multiple myeloma
3. History of active malignancy during the past 5 years, except squamous cell and basal cell carcinomas of the skin and carcinoma in situ of the cervix or breast and incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is cured, or malignancy that in the opinion of the local investigator, with concurrence with the principal investigator, is considered cured with minimal risk of recurrence within 3 years.
4. Participant with any one of the following: clinically significant abnormal electrocardiogram (ECG) findings at screening; congestive heart failure (New York Heart Association Class III or IV); myocardial infarction within 12 months prior to starting iberdomide; unstable or poorly controlled angina pectoris, including Prinzmetal variant; clinically significant pericardial disease
5. Peripheral neuropathy of ≥grade 2.
6. Participant has any concurrent severe and/or uncontrolled medical condition or psychiatric disease that is likely to interfere with trial procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this trial or that confounds the ability to interpret data from the trial.
7. Participant with gastrointestinal disease that may significantly alter the absorption of iberdomide
8. Participant with known history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide, pomalidomide
9. Participant with known or suspected hypersensitivity to excipients contained in the formulation of iberdomide
10. Participant has current or prior use of immunosuppressive medication within 14 days prior to starting therapy with iberdomide (exceptions are intranasal, inhaled, topical or local steroids injections; systemic corticosteroids at doses not exceeding 10 mg/day of prednisone or equivalent; steroids as premedication for hypersensitivity reactions)
11. Participant has taken a strong inhibitor or inducer of CYP3A4/5 including grapefruit, St John’s wort or related products within 2 weeks prior to dosing and during the course of trial
12. Participant known to test positive for HIV or have active hepatitis A, B or C
13. Participant is unable or unwilling to undergo protocol required thromboembolism prophylaxis
14. Participant is a female who is pregnant nursing or breastfeeding or who intends to become pregnant during the participation
15. Baseline lab values: - Creatinine clearance ≤30 ml/min. - Significant hepatic dysfunction (total bilirubin > 1.5x ULN or AST/ALT > 2.5x ULN), or > 3.0 mg/dL for participants with documented Gilbert’s syndrome unless related to myeloma - Corrected serum calcium>13.5 mg/dL (3.4 mmol/L)
16. Any clinical condition at screening that would preclude participant from completing the trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Response improvement rate within 6 months will be measured as the number of participants that improve response according to IMWG criteria (from PR to ≥VGPR; from VGPR to ≥CR; from CR to >sCR) within the end of sixth cycle of treatment.

Secondary endpoints 16

1. TTP will be measured by protocol from the date of start of therapy and according to ITT from the date of eligibility confirmation to the date of first observation of PD, or deaths for PD. Participants who have not progressed or who withdraw from the trial or die from causes other than PD will be censored at the time of the last disease assessment. Participants lost to FU will also be censored at the time of last complete disease assessment.
2. PFS will be measured by protocol from the date of start of therapy and according to ITT from the date of eligibility confirmation to the date of first observation of PD, or death from any cause as an event. Participants who have not progressed or who withdraw from the trial or who were lost to FU will be censored at the time of the last disease assessment.
3. TNT will be measured by protocol from the date of start of therapy and according to ITT from the date of eligibility confirmation to the date of next anti-myeloma therapy. Death due to any cause before starting therapy will be considered an event. Participants who have not progressed or who withdraw from the trial will be censored at the time of the last disease assessment. Participants lost to FU will also be censored at the time of last contact.
4. PFS2 will be measured by protocol from the date of start of therapy and according to ITT from the date of eligibility confirmationto the date of observation of second disease progression (i.e. progression after the second line of therapy) or death to any cause as an event. In case of date of second progression is not available, date of start of third line treatment can be used.
5. OS is defined by protocol from the date of start of therapy and according to ITT from the date of eligibility confirmation to the date of death, regardless cause of death. Participants who withdraw consent will be censored at the time of withdrawal. Participants who are still alive at the cut-off date of final analysis will be censored at the date of last contact. Participants lost to FU will also be censored at the time of last contact.
6. Response rate (sCR, CR, VGPR) will be evaluated according to IMWG Response criteria
7. Rate of NGF Minimal residual disease (MRD) conversion from positive to negative
8. The MRD conversion rate at 6 months is determined as the proportion of participants with MRD negativity (≥10-5 sensitivity level, by NGF) after 6 months converted from status as Positive at screening.
9. The MRD conversion rate at 12 months is determined as the proportion of participants with MRD negativity (≥10-5 sensitivity level, by NGF) after 12 months converted from status as Positive at screening. Participants who withdraw from the trial or are lost to follow up before post 12 months MRD evaluation, the best MRD assessment will be considered.
10. The best MRD conversion rate within 12 months is determined as the proportion of participants with MRD negativity (≥10-5 sensitivity level, by NGF) within 12 months converted from status as Positive at screening. The best MRD assessment will be considered. Participants who withdraw from the trial or are lost to follow up before MRD evaluation, the best MRD assessment will be considered.
11. The analysis of safety as defined by type, frequency and severity will be done primarily by tabulation of the incidence of AEs as defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. In the by-participant analysis, a participant having the same event more than once will be counted only once. AEs will be summarized by worst CTCAE grade
12. Dose reduction will be done primarily by tabulation of the incidence of participant with at least one dose reduction and causes.
13. Relative dose will be evaluated consider the ratio between the administered and the planned dose.
14. Time to discontinuation for toxicity will be measured from the date of first dose of study drugs to the date of discontinuation due to AE or Death for AE/SPM. Participants who discontinued drugs due to PD, or death for cause other than AE/SPM will be considered a competing event. Participants has not discontinued and are still alive and on treatment at the cut-off date of final analysis will be censored at the cut-off date.
15. Quality of life defined by EORTC QLQ-C30.
16. Determine whether tumor response and outcome (PFS, PFS2, TTP, TNT and OS) may change in subgroups with different prognosis according to current prognostic factors.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

European Myeloma Network B.V.

Sponsor organisation

European Myeloma Network B.V.

Address

Blaak 555

City

Rotterdam

Postcode

3011 GB

Country

Netherlands

Scientific contact point

Organisation

European Myeloma Network B.V.

Contact name

Mario Boccadoro

Public contact point

Organisation

European Myeloma Network B.V.

Contact name

Pieter Sonneveld

Third parties 8

Emn Trial Office S.r.l. Impresa Sociale

Sponsor organisation

Emn Trial Office S.r.l. Impresa Sociale

Address

Via Saluzzo 1/a, TO

City

Turin

Postcode

10125

Country

Italy

Scientific contact point

Organisation

Emn Trial Office S.r.l. Impresa Sociale

Contact name

Mario Boccadoro

Public contact point

Organisation

Emn Trial Office S.r.l. Impresa Sociale

Contact name

Mario Boccadoro

Sponsor responsibilities

Article 77 compliance

European Myeloma Network B.V.

Contact point sponsor

European Myeloma Network B.V.

Article 77 implementation

European Myeloma Network B.V.

Locations

4 EU/EEA countries · 19 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 47 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications