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Multiple Myeloma, RefractoryPhase 1AcTRESSNCT06411301

A Phase I Study to Assess the Tolerability of 225Ac-DOTATATE in Patients With Refractory and Relapsing Multiple Myeloma Expressing Somatostatin Receptors

A Phase 1 study testing 225Ac-DOTATATE in people with Multiple Myeloma, Refractory and Multiple Myeloma in Relapse, run by Jules Bordet Institute at 1 site in Belgium.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This study aims to determine the safety and the recommended phase II dose of RYZ101 (actinium-225 labelled DOTA-octreotate (225Ac-DOTATATE)) in participants with refractory and relapsing multiple myeloma (MM) that have received at least 3 prior lines of myeloma therapy. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
225Ac-DOTATATE
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteBelgium
Study dates
Oct 2024to Oct 2026
Phase
Phase 1
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent in accordance with institutional guidelines and obtained prior to any study procedure
  • Age of at least 18 years at the time of signing the informed consent
  • Confirmed diagnosis of multiple myeloma according to the Salmon and Durie criteria
  • Have received at least 3 prior lines of myeloma therapy including an immunomodulatory drug, a proteasome inhibitor and an anti-CD38 antibody
  • Must have progressed on their last line of myeloma therapy
  • Biologically active (relapsing or refractory) and measurable disease as defined by at least one of the following:
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  • Serum M-protein ≥ 0.5 g/dL by serum protein electrophoresis (SPEP) or, for immunoglobulin (Ig) A myeloma, by quantitative IgA
  • Urinary M-protein of at least 200 mg/24 hours by urine protein electrophoresis
  • Serum free light chain (FLC) ≥ 100 mg/L, provided that FLC ratio is abnormal
  • If SPEP is felt to be unreliable for routine M-protein measurement (example, for IgA or IgD MM), then quantitative Ig levels by nephelometry or turbidimetry are acceptable
  • Estimated life expectancy above 6 months
  • Eastern Cooperative Oncology Group performance status ≤ 1
  • Bone marrow aspiration and biopsy sample available within 30 days prior study enrolment (optional under the subject agreement)
  • Baseline PET/CT imaging scans defined by:
  • 68Ga-DOTATATE PET/CT-positive imaging with target lesions, defined as unequivocal tumoral uptake higher than the maximum standardized uptake value of the femoral bone marrow background
  • All 18F-FDG PET/CT-avid lesions must be SSTR-positive, as defined above
  • Adequate renal function as measured by renal scintigraphy scans and evidenced by creatinine clearance (CrCl) ≥60 mL/min/1.73m^2
  • Adequate hematologic function defined by the following laboratory results:
  • Hemoglobin concentration ≥5.0 mmol/L (≥8.0 g/dL)
  • Total white blood cell count ≥1.5 × 103/mm^3
  • Absolute neutrophil count ≥1000 cells/µL (≥1000 cells/mm^3)
  • Platelets count >100 × 10^9/L (100 × 10^3/mm^3)
  • Adequate hepatic function defined by the following laboratory results:
  • Aspartate aminotransferase and alanine aminotransferase ≤2.5 × upper limit of normal (ULN) (or ≤5 × ULN if presence of liver metastases)
  • Total bilirubin ≤3 × ULN
  • Serum albumin ≥3.0 g/dL
  • Adequate coagulation function, defined by international normalized ratio or prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤1.5 × ULN, unless subject is receiving anticoagulant therapy and PT or aPTT is within therapeutic range of intended use of anticoagulants
  • For women of childbearing potential (WOCBP):
  • Negative serum pregnancy test within 48 hours prior to the first dose of study treatment
  • Agreement to use barrier contraception and a second form of highly effective contraception (Clinical Trials Facilitation Group (CTFG) 2020) while receiving study treatment and for 7 months following their last dose of study treatment
  • Sexually active male subjects must use a condom during intercourse while receiving study treatment and for at least 120 days after the last dose of the study drug and should not father a child during this period
  • Male study subjects whose sexual partners are WOCBP must also agree to use a second form of highly effective contraception (CTFG 2020) while receiving study treatment and for at least 4 months following their last dose
  • Vasectomized men are also required to use a condom during intercourse, including with a male partner

Who cannot join

  • Massive bone marrow infiltration on the baseline 68Ga-DOTATATE PET/CT scan
  • History of hypersensitivity or allergy to 225Ac, 68Ga, octreotate, or any of the excipients of DOTATATE imaging agents
  • Use of anticancer agents within the following intervals prior to the first dose of study drug:
  • Chemotherapy: within <6 weeks
  • Small molecule inhibitors: within <4 weeks
  • Biological agents: within <7 days or <5 half-lives
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  • Prior external beam radiotherapy on more than 25% of bone marrow
  • Prior participation in any interventional clinical study within 30 days prior to first dose of study drug
  • Have a history of primary malignancy within the past 3 years other than (1) MM; (2) adequately treated carcinoma in situ or non-melanoma carcinoma of the skin; (3) any other curatively treated malignancy that is not expected to require treatment for recurrence during participation in the study, or (4) an untreated cancer on active surveillance that may not affect the subject's survival status for ≥3 years based on clinician assessment/statement
  • Any toxicities from prior treatments that have not recovered to CTCAE Grade ≤1 at baseline, except for alopecia
  • Significant cardiovascular disease, defined as:
  • New York Heart Association (NYHA) Class ≥II heart failure
  • Known left ventricular ejection fraction <50%
  • History of myocardial infarction, acute coronary syndrome, or coronary angioplasty/stenting/bypass within the last 6 months
  • QT interval corrected for heart rate using Fridericia's formula >470 ms, demonstrated by the average value of 3 consecutive electrocardiograms
  • Resistant hypertension, defined as persistent uncontrolled blood pressure >140/90 mmHg (diastolic/systolic) while on optimal doses of at least 3 antihypertensive medications with 1 being a diuretic
  • Uncontrolled diabetes mellitus as defined by hemoglobin A1C >8%
  • Impossibility to discontinue corticoids administration at a therapeutic level (total dose of 160 mg of dexamethasone or equivalent) two weeks prior dosing of study drug
  • Pregnancy or lactation
  • Any known or underlying medical, psychiatric disease/condition, and/or social situations that, in the opinion of the investigator, would limit compliance with study requirements

Trial locations and contacts

1 site in 1 country.

Belgium1 site

  • Jules Bordet Institute

    Brussels, 1070

Other trials in Belgium

About this study

This study aims to determine the safety and the recommended phase II dose of RYZ101 (actinium-225 labelled DOTA-octreotate (225Ac-DOTATATE)) in participants with refractory and relapsing multiple myeloma (MM) that have received at least 3 prior lines of myeloma therapy. Participants will be selected based on somatostatin receptor (SSTR) positivity assessed by gallium-68 labelled DOTA-octreotate (68Ga-DOTATATE) PET/CT. The response to 225Ac-DOTATATE therapy will also be assessed in the target study population.

Being tested
225Ac-DOTATATE
Keywords
Multiple Myeloma, Somatostatin receptor, Radionuclide therapy, Actinium-225, Targeted alpha therapy
Medical subject headings
Multiple Myeloma

What participants receive

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

  • 225Ac-DOTATATEDrug

    Also called RYZ101

    Two intravenous infusions every 6 weeks (Q6W)

Study groups in NCT06411301
Study groupRoleWhat they receive
225Ac-DOTATATEExperimentalDose escalation study to assess the safety and determine the recommended phase II dose, based on time-to-event Bayesian optimal interval design, with a target toxicity rate of 30%. Three dose levels are planned to be evaluated: 5 MBq (starting dose), 7.5 MBq and 10 MBq (maximum dose allowed). The cohort size will be 3, with a maximum of 10 participants within a same dose level, and a maximum of 18 evaluable participants in total. Participants are planned to receive two cycles of intravenous infusion of 225Ac-DOTATATE every 6 weeks (Q6W). Each dose escalation and potential de-escalation step will be decided based on the dose-limiting toxicities (DLT) rate observed during the study treatment period (84 days following the first infusion), in the current dose cohort.
Receives: Drug: 225Ac-DOTATATE

What is being measured

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

  1. Safety and tolerability of 225Ac-DOTATATE

    Incidence and severity of adverse events (AEs) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0

    Measured: First 84 days following first 225Ac-DOTATATE injection

  2. Recommended phase II dose of 225Ac-DOTATATE

    Rate incidence of dose-limiting toxicities (DLT)

    Measured: First 84 days following first 225Ac-DOTATATE injection

Secondary outcomes (1)

  1. Clinical activity of treatment with 225Ac-DOTATATE

    Overall response according to the International Myeloma Working Group (IMWG) response criteria

    Measured: First 84 days following first 225Ac-DOTATATE injection

Timeline

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

  1. First posted13 May 2024
  2. Study startOct 2024 (estimated)
  3. Primary completionOct 2026 (estimated)
  4. Study completionOct 2026 (estimated)

Why it stopped: Sponsor decision

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06411301
Sponsor's protocol ID
IJB-MN-AcTRESS
Acronym
AcTRESS
Status last verified
Jan 2025
First submitted
8 May 2024
Last updated
31 Jan 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 225Ac-DOTATATE in people with Multiple Myeloma, Refractory and Multiple Myeloma in Relapse, run by Jules Bordet Institute at 1 site in Belgium.

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 33 inclusion and 20 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 31 Jan 2025. 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 Belgium. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Safety and tolerability of 225Ac-DOTATATE (time frame: First 84 days following first 225Ac-DOTATATE injection). The study lists 2 primary outcomes in all. 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 NCT06411301.

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 31 Jan 2025.

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