A randomized phase III trial assessing iberdomide versus iberdomide plus isatuximab maintenance therapy post autologous hematopoietic stem-cell transplantation in patients with newly diagnosed multiple myeloma (GMMG-HD9/DSMM XVIII-trial)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsklinikum Heidelberg AöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15], Diseases [C] - Neoplasms [C04]

Trial duration

3 Apr 2024 → ongoing

Decision date (initial)

2025-01-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Bristol Myers Squibb · Sanofi-Aventis Deutschland GmbH

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

Demonstration of superiority of iberdomide plus isatuximab compared to iberdomide with respect to bone marrow minimal residual disease (MRD) negativity rates (sensitivity 2x10^-6 via next-generation flow cytometry [NGF]) after two years of maintenance therapy.

Secondary objectives 1

1. Demonstration of superiority of iberdomide plus isatuximab compared to iberdomide with respect to progression-free survival (PFS).

Conditions and MedDRA coding

Multiple myeloma

Study design 1 period

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Patients meeting all of the following criteria will be considered for admission to the trial: Prior inclusion and treatment within the GMMG-HD8/DSMM XIX trial (including confirmation of diagnosis of MM with myeloma-defining events [end-organ damage or biomarker of malignancy] and measurable disease prior to initiation of induction therapy as outlined in the IMWG criteria)
2. Received at least one cycle high dose melphalan therapy (HDM) and autologous stem cell transplantation (ASCT)
3. At least Partial Response (PR) according to IMWG criteria at inclusion in the trial
4. Age of 18 years or higher at trial inclusion
5. WHO performance status of 0, 1, or 2 (see Appendix II)
6. 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 (ie, has had menses at any time in the preceding 24 consecutive months) and must: a) Have two negative serum or urine pregnancy tests as verified by the Investigator prior to starting study treatment. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence from heterosexual contact. b) 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 study treatment (including dose interruptions), and for at least 28 days after the last dose of iberdomide.
7. Male subjects must practice complete abstinence (True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence [e.g. calendar, ovulation, symptothermal or post-ovulation methods] and withdrawal are not acceptable methods of contraception) or agree to use a condom during sexual contact with a pregnant female or a FCBP while taking iberdomide, during dose interruptions and for at least 28 days following the last dose of iberdomide even if he has undergone a successful vasectomy.
8. Males must agree to refrain from donating sperm while on study treatment, during dose interruptions and for at least 28 days following last dose of study treatment.
9. All male and female subjects must follow all requirements defined in the Pregnancy Prevention Program (see section 7.1.7 and Appendix IV).
10. All patients must agree to abstain from donating blood while taking study treatment and for 28 days following discontinuation of study treatment
11. Ability of patient to understand character and individual consequences of the clinical trial
12. Written informed consent (must be available before enrolment in the trial)

Exclusion criteria 25

1. Patients presenting with any of the following criteria will not be included in the trial: Subjects with gastrointestinal disease that may significantly alter the absorption of iberdomide
2. Patients with severe renal insufficiency (Creatinine Clearance < 30 mL/min) or requiring hemodialysis
3. Patients with peripheral neuropathy or neuropathic pain, grade 2 or higher (as defined by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE, version 5.0, see Appendix V)
4. Patients with a history of any active malignancy during the past 5 years with the exception of following malignancies after curative therapy: basal cell carcinoma of the skin, squamous cell skin carcinoma, stage 0 cervical carcinoma or any in situ malignancy. A history of an early stage malignancy during the past 5 years may be acceptable, however, in this case the GMMG or DSMM study office has to be consulted prior to study inclusion
5. Patients with acute diffuse infiltrative pulmonary and/or pericardial disease
6. Autoimmune haemolytic anaemia with positive indirect Coombs test or immune thrombocytopenia
7. Platelet count < 75 x 10^9/L
8. Haemoglobin ≤ 8.0 g/dL, unless related to MM
9. Absolute neutrophil count (ANC) < 1.0 x 10^9/L (the use of colony stimulating factors within 14 days before the test is not allowed)
10. Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L)
11. Unable or unwilling to undergo thromboprophylaxis
12. • Patient has known hypersensitivity or contraindication to any of the components of study therapy (e.g. known intolerance or hypersensitivity to iberdomide, isatuximab, infused proteins products, sucrose, histidine, and polysorbate 80 as well as intolerance to arginine and Poloxamer 188)
13. Pregnancy and lactation
14. Participant has any concurrent severe and/or uncontrolled medical condition or psychiatric disease that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study or that confounds the ability to interpret data from the study
15. Participation in other interventional clinical trials. This does not include long-term follow-up periods without active drug treatment of previous studies during the last 6 months
16. Systemic AL amyloidosis (except for localized AL amyloidosis limited to the skin or the bone marrow) or plasma cell leukemia (> 2.0 × 109/L circulating plasma cells by standard differential blood count) or polyneuropathy, organomegaly, endocrinopathy, monoclonal-protein and skin abnormalities (POEMS syndrome); or Waldenström macroglobulinemia.
17. Previous systemic anti-myeloma treatment other than administered within the GMMG-HD8 / DSMM XIX trial (including up to two cycles cycle high dose melphalan therapy (HDM) and autologous stem cell transplantation (ASCT). Local, consolidative radiotherapy for myeloma disease is permitted unless performed in case of progressive disease (PD) according to IMWG criteria
18. Severe cardiac dysfunction (NYHA classification III-IV; see Appendix II)
19. Significant hepatic dysfunction (ASAT and/or ALAT ≥ 3 times normal level and/or serum bilirubin ≥ 1.5 times normal level if not due to hereditary abnormalities as Gilbert’s disease), unless related to MM or HDM/ASCT
20. • Patients with active or uncontrolled hepatitis B or C or detectable liver disease due to hepatitis B or C. In case of history of hepatitis B or C, it must be clarified whether it has been overcome and negative circulating HBV-DNA or HCV-RNA with sensitive PCR blood tests must be provided. Positive hepatitis B status may only be acceptable in absence of circulating HBV-DNA or signs of chronic or acute infection and if an adequate prophylaxis is being implemented during the course of the study. Prophylaxis for patients with history of hepatitis B or C should be set on a patient individual basis
21. HIV positivity
22. Patients with active, uncontrolled infections
23. • Patients with a history of serious allergic reaction to another immunomodulatory agent (thalidomide, lenalidomide, or pomalidomide), as angioedema and severe dermatologic reactions, including Grade 4 rash and exfoliative or bullous rash
24. • Patients currently being treated with medically indispensable strong inhibitors or inducers of CYP3A4/5
25. • Subjects, who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Rates of NGF-MRD negativity (sensitivity 2x10-6, from bone marrow aspirate [BMA]) after two years of maintenance therapy.

Secondary endpoints 1

1. PFS, defined as time from randomization to disease progression or death from any cause, whichever occurs first.

Investigational products

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

Test 5

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsklinikum Heidelberg AöR

Sponsor organisation

Universitaetsklinikum Heidelberg AöR

Address

Im Neuenheimer Feld 672, Neuenheim Neuenheim

City

Heidelberg

Postcode

69120

Country

Germany

Scientific contact point

Organisation

Universitaetsklinikum Heidelberg AöR

Contact name

GMMG Studiensekretariat

Public contact point

Organisation

Universitaetsklinikum Heidelberg AöR

Contact name

GMMG Studiensekretariat

Locations

2 EU/EEA countries · 81 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 33 files

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

Application history

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