KRd consolidation in myeloma patients with a positive PET-CT after standard first line treatment. A phase II study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Oslo University Hospital HF

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Diseases [C] - Neoplasms [C04]

Trial duration

30 Jan 2018 → 20 May 2025

Decision date (initial)

2024-10-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Amgen

External identifiers

EU CT number

2024-511714-20-00

EudraCT number

2017-000586-72

ClinicalTrials.gov

NCT03314636

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To assess the proportion of patients that are PET-positive after standard first line treatment, and how many of these can become PET-negative after 4 cycles of KRd consolidation.

Secondary objectives 1

1. The correspondence between PET-CT results and MRD dynamics by intra-patient comparison

Conditions and MedDRA coding

Multiple Myeloma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. At least 18 years of age, with at least 6 months expected survival.
2. Prior confirmed diagnosis of multiple myeloma (2014)
3. Received standard first line treatment with at least a very good partial response (VGPR), according to IMWGs criteria . Standard first line treatment is defined as VRD, VTD or VCD followed by ASCT with or without lenalidomide maintenance initiated (Patients where the monoclonal component or dFLC increases during the period from best response to screening can be included if there is no progressive disease.)
4. Patients must be carfilzomib naïve.
5. A positive PET-CT result from central reviewer in the screening period
6. Successful FISH evaluation performed with available results
7. Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that the patient may withdraw consent at any time without prejudice to future medical care.
8. Females of childbearing potential (FCBPs) must have a confirmed negative serum pregnancy test within the 7 days prior to inclusion
9. FCBPs and male subjects who are sexually active with FCBP must agree to use highly effective concomitant methods of contraceptive during the study and for 30 days following the last study drug dose. Male subjects must use contraception and refrain from donating sperm for at least 90 days after the last dose of carfilzomib.
10. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. In patients >75 years of age, performance status 0-1.
11. Patients must meet the following adequate organ and bone marrow function within 21 days prior to inclusion: • Absolute neutrophil count (ANC) ≥ 0,5 x 109/L) and platelet count 35 x 109/L. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment. Granulocyte growth factors are allowed to meet the inclusion criteria.
12. Patient must be willing and able to adhere to the study schedule and other protocol requirements.

Exclusion criteria 20

1. Change of first line treatment because of stable or progressive disease.
2. Female patients who are lactating or have a positive serum pregnancy test during the screening period.
3. Major surgery within 28 days before enrollment.
4. Radiotherapy within 14 days before enrollment. Glucocorticoid therapy within the 14 days prior to inclusion that exceeds a cumulative dose of 160 mg dexamethasone or 1000 mg prednisone.
5. Patients who started treatment more than 12 month before screening
6. Central nervous system involvement.
7. Uncontrolled heart disease, including congestive heart failure (NYHA III-IV), uncontrolled angina pectoris, uncontrolled conduction abnormalities, acute diffuse infiltrative pulmonary disease, pericardial disease or myocardial infarction within 6 months prior to enrollment
8. Active hepatitis B or C infection or known human immunodeficiency virus (HIV) positivity.
9. Any other serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol.
10. Known allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib) or to any of the study medications, their analogues, or excipients in the various formulations of any agent.
11. Contraindication to dexamethasone or any of the required concomitant drugs or supportive treatments, including hypersensitivity to antiviral drugs, or intolerance to hydration due to pre-existing pulmonary or cardiac impairment.
12. Another active malignancy. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
13. Patients that have previously been treated with carfilzomib.
14. Primary plasma cell leukemia, systemic AL amyloidosis, Waldenströms macroglobulinemia, POEMS syndrome
15. Pleural effusions requiring thoracocentesis within the 14 days prior the inclusion
16. Ascites requiring ascites puncture within the 14 days prior to inclusion.
17. Previous allogeneic transplantation
18. Uncontrolled hypertension or uncontrolled diabetes despite medication
19. Contraindication to PET-CT
20. Not expected to tolerate full dose KRd

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Proportion of PET-CT positivity after standard first line therapy
2. Change from PET-CT positivity to PET-CT negativity after 4 cycles of KRd consolidation.

Secondary endpoints 7

1. MRD negativity by 8-colour EuroFlow after 4 cycles of KRD consolidation.
2. Safety
3. Overall response rate
4. Progression-free survival (PFS)
5. Time to next treatment (TTNT)
6. Overall survival (OS)
7. Quality of life during and after KRD consolidation

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Oslo University Hospital HF

Sponsor organisation

Oslo University Hospital HF

Address

Taarnbygget, Kirkeveien 166 Kirkeveien 166

City

Oslo

Postcode

0450

Country

Norway

Scientific contact point

Organisation

Oslo University Hospital HF

Contact name

Fredrik Schjesvold

Public contact point

Organisation

Oslo University Hospital HF

Contact name

Fredrik Schjesvold

Locations

2 EU/EEA countries · 3 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 15 files

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

Application history

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