High Risk Smoldering Multiple MyelomaNCT06745687
BCMA/CD3 BsAb in the Treatment of High-risk Smoldering Multiple Myeloma
A study testing CM336 in people with High Risk Smoldering Multiple Myeloma, run by Institute of Hematology & Blood Diseases Hospital, China at 1 site in China.
Trial summary
The purpose of this study is to evaluate the safety and efficacy of CM-336, which is a BCMA/CD3 BiTE, in the treatment of high risk smoldering multiple myeloma. Read more about this study
- Who is it for?
- Ages 18 to 78 yearsHealthy volunteers can take part
- Conditions the study is for
- High Risk Smoldering Multiple Myeloma
- What is being tested?
- CM336
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 30 Dec 2024to 1 Aug 2029
- Phase
- Interventional
- 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 78 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Know and voluntarily sign an informed consent form (ICF).
- Age ≥18 years.
- Definite diagnosis of SMM: According to IMWG Criteria 10, the patient must have histologically or cytologically confirmed smoldering multiple myeloma (SMM), including:
- Serum M protein ≥3 g /dL and/or BMPCs≥10%(but not more than 60%)
- No anemia: hemoglobin ≥10 g /dL
- No renal failure: serum creatinine ≥2.0 mg/dL
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- No hypercalcemia: calcium ≥10.5 mg/dL
- dissolving bone lesions without radiographic indications: X-ray, CT, or positron emission tomography (PET)/CT without dissolving bone lesions, with no more than 1 lesion on whole-body MRI (Note: In the investigator's judgment, whole-body CT or PET/CT may replace MRI for patients with contraindications or for whom MRI is not available).
- FLC ratio <100 (unless light chain ≤10 mg /dL is involved) Note: Anemia, renal failure and hypercalcemia are allowed if there is evidence that anemia, renal failure, hypercalcemia or bone lesions are not associated with multiple myeloma (MM).
- High-risk SMM are defined as meeting one or more of the three criteria in the following part: (i) Mayo 2018, (ii) IMWG 2020 and (iii) evolving pattern.
- (i)Mayo 2018
- M protein > 2 g/dL ② The ratio of affected to unaffected FLC was > 20 ③BMPC > 20% of the 3 items meet any 2 or more
- IMWG 2020
- FLC ratio 0-10: 0 points 10-25: 2 points 25-40: 3 points >40: 5 points
- ②M protein (g/dL) 0-1.5: indicates 0 points 1.5-3: 3 points >3: 4 points
- ③BMPC (%) 0-15: 0 points 15-20: 2 points 20-30: 3 points 30-40: 5 points >40: 6 points
- ④FISH : Yes: 2 points None: 0 points The sum of the four points is greater than or equal to 9 (iii)Progression model
- Necessary condition: BMPC>10% ② Sufficient conditions: a. Serum M protein >3 g/dL b. IgA type SMM c. Immune paralysis (reduction of two uninvolved homologous immunoglobulins) d. The proportion of free light chain (FLC) in serum that is affected/not affected > 8 (but <100) e.M protein level increased (SMM type increased; Serum M protein level was increased by ≥25% twice in 6 months.
- F.BMPC: 50%-59% g. Abnormal plasma cell immunophenotype (95% + of cloned BMPC) and reduction of one or more uninvolved immunoglobulin types.
- h.≥5% of cells had chromosomal abnormalities (t (4,14) or del 17 p or 1 q acquisition i. Increased circulating plasma cells (PCs>5×106/L or 5%) j. Merri indicates diffuse abnormalities or 1 focal lesion, and/or increased uptake of focal lesion in PET-CT class without underlying osteolytic osteopathy. Meet the necessary conditions, 1 or more sufficient conditions.
- FISH exceptions are defined as the presence of any of the following: t (4,14), t (14,16), 1 q amplification, del 13 qt, t (4,20)
- ECOG physical status score ≤2 points.
- Meeting the following laboratory indicators within 28 days prior to study participation:
- neutrophils absolute value (ANC) >1000/ml b. Platelet count (PLC)> 75,000 /ml c. Total bilirubin ≤2 mg/dL d. Glutamic oxalic aminotransferase (AST) <2.5 times the conventional upper limit (ULN) e. Alanine aminotransferase (ALT) <2.5 times the upper limit of normal (ULN) f. Estimated creatinine clearance (CLcr)≥60 mL/min.
- Non-childbearing women meet the entry requirements; Female patients of childbearing age must have a negative serum (beta-human chorionic gonadotropin) or urine pregnancy test at the time of screening.
- Men, women of childbearing age, and their partners voluntarily use contraception deemed effective by investigators during treatment and for at least three months after CAR T cell transfusion.
- Male patients must agree not to donate sperm from the initial screening period until 90 days after the last medication.
- Patients must be willing and able to complete study procedures and follow-up examinations.
- Note: Fertile women are all women who have begun menstruating and are not in late menopause and who have not undergone surgical sterilization (e.g., hysterectomy, bilateral tubal ligation, bilateral oophorectomy). Postmenopause is defined as more than 12 consecutive months of amenorrhea for an unspecified reason. Women who are using mechanical birth control methods such as oral contraceptives or intrauterine devices should be considered fertile. Male subjects (including those who have undergone vasectomy) must consent to the use of condoms during sex with women of childbearing age and must not plan to impregnate the woman during the study drug use period from the date of signing the informed consent form and within 3 months after the last study drug receipt.
Who cannot join
- Diagnosis of symptomatic multiple myeloma: refer to the Chinese Guidelines for Diagnosis and Treatment of multiple myeloma (revised in 2022);
- Along with other tumors that must be treated.
- Previously received immunotherapy against BCMA targets.
- The researchers judged that BCMA/CD 3 dual antibody therapy is not suitable, such as severe cardiopulmonary disease and other conditions that are not suitable for BCMA/CD 3 dual antibody therapy.
- Received SMM treatment within six months.
- Known intolerance, allergy or contraindications to BCMA/CD 3 dual anti-active ingredients.
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- Patients with unstable or active cardiovascular and cerebrovascular diseases meet any of the following criteria:
- Unstable angina pectoris, symptomatic myocardial ischemia, myocardial infarction, or coronary artery reconstruction had occurred within 180 days prior to initial administration.
- Uncontrolled hypertension (>140/90 MMHG, with a blood pressure fluctuation of more than 180/100 MMHG over 6 months);
- Uncontrolled and clinically significant conduction abnormalities (e.g., patients with ventricular arrhythmias controlled by antiarrhythmic drug therapy), not excluding patients with first-degree AV block or asymptomatic left anterior bundle branch block/right bundle branch block (LAFB/RBBB);
- Echocardiographic left ventricular ejection fraction (LVEF) < 40%;
- History of stroke or intracranial hemorrhage within 12 months prior to screening;
- Severe thrombotic events before treatment.
- 9) Known active human immunodeficiency virus (HIV) infection or HIV seropositivity.
- 10) Active hepatitis B or C infection. Screening requires hepatitis serological testing. If hepatitis B surface antigen is positive, a negative DNA polymerase chain reaction (PCR) result is required to be confirmed before enrollment (after anti-HBV treatment, a negative DNA polymerase PCR result is required before enrollment). If the hepatitis C antibody is positive, an RNA PCR test is performed and the result before enrollment is confirmed to be negative.
- 11) Pregnant or lactating women. 12) Any active gastrointestinal dysfunction that affects the patient's ability to swallow pills, or any active gastrointestinal dysfunction that may affect the absorption of investigational therapeutic drugs.
- 13) Patients had major surgery (for example, requiring general anesthesia) within 2 weeks before enrollment began, or will not fully recover from surgery, or have surgery scheduled during the time they plan to participate in the study. Kyphoplasty or spondyloplasty is not considered major surgery. Note: Patients who plan to perform surgery under local anesthesia may participate in the study.
- 14) Received live attenuated vaccine within 4 weeks prior to administration of the first investigational drug.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences
Tianjin
Gang An, MD&PhD, +86-022-23909171, angang@ihcams.ac.cn
About this study
Official title: A Prospective, Multi-center, Single-arm Clinical Trial of BCMA/CD3 BsAb in the Treatment of High-risk Smoldering Multiple Myeloma
The purpose of this study is to evaluate the safety and efficacy of CM-336, which is a BCMA/CD3 BiTE, in the treatment of high risk smoldering multiple myeloma.
Read the detailed description
The purpose of this study is to evaluate the safety and efficacy of CM-336, which is a BCMA/CD3 BiTE, in the treatment of high risk smoldering multiple myeloma.
High-risk SMM has a high risk of transforming to MM, and there is no unified treatment plan in clinical practice at present. Studies have proved that early treatment can help prevent end organ damage caused by disease progression and improve patient prognosis. The treatment of high-risk SMM needs to be further explored. BCMA/CD3 BITE in the treatment of RRMM shows a high remission rate and low toxicity and side effects, and it is expected to become a potential treatment choice for high-risk SMM patients
- Conditions
- High Risk Smoldering Multiple Myeloma
- Being tested
- CM336
- Keywords
- high risk smoldering multiple myeloma, BCMA/CD3 BiTE, CM-336
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CM336Drug
Patients received subcutaneous CM-336 80 mg once weekly in 28-d cycles after two step-up priming doses of 3 mg and 20 mg given on day 1 and day 4 of cycle 1 and cycle2. Then patients will be given 160mg every 2 weeks from cycle 3 to cycle 6. The dosing interval is adjusted according to the evaluation of efficacy every 6 cycles from cycle 7 to cycle 24.
| Study group | Role | What they receive |
|---|---|---|
| CM-336( BCMA/CD3 bispecific antibody) | Experimental | Patients enrolled in the trial will receive CM336 subcutaneously, which is an BCMA/CD3 bispecific antibody therapy. Receives: Drug: CM336 |
What is being measured
The primary outcome is the main question the study is designed to answer.
minimal residual disease netativity(MRD negativity)
The proportion of abnormal plasma cells occupying nuclear cells in the samples
Measured: baseline, 28 days per cycle, cycle 6 day 28, cycle 12 day 28, cycle 18 day 28, cycle 24 day 28, 1 year and 2 year after end of treatment.
Secondary outcomes (6)
time to response
Time from randomization to first documentation of hematologic response
Measured: up to 2 years
Hematologic response rate
Overall hematologic (CR + VGPR + PR) response rate based on central laboratory results based on 2016 IMWG response criteria.
Measured: up to 2 years
Adverse events and serious adverse events
Adverse events (AEs), serious adverse events (SAEs), and assessments of clinical laboratory values
Measured: up to 2 years
progression free survival(PFS)
progression free survival defined as time from randomization to date of hematologic progression or documented disease progression (PD). Patients without documentation of death at the time of analysis were censored at the date last known to be alive
Measured: up to 2 years after end of therapy
overall survival(OS)
Time from randomization to date of death. Patients without documentation of death at the time of analysis were censored at the date last known to be alive
Measured: up to 2 years after end of therapy.
duration of response(DOR)
DOR is defined as the time from initiation of first response to first documentation of disease progression or death whichever occurs first. Patients without documentation progressed or died are censored at the date last known progression-free.
Measured: up to 2 years after end of therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2024
- Study start30 Dec 2024
- Primary completion1 Aug 2027 (estimated)
- Study completion1 Aug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for High Risk Smoldering Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Institute of Hematology & Blood Diseases Hospital, ChinaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- A single-arm multi-center trial
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Keymed Biosciences Co.Ltd
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06745687
- Sponsor's protocol ID
- IIT2024009
- Status last verified
- Jul 2026
- First submitted
- 10 Dec 2024
- Last updated
- 23 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Multi-center, Single-arm Clinical Trial of BCMA/CD3 BsAb in the Treatment of High-risk Smoldering Multiple Myeloma
- ClinicalTrials.gov ID
- NCT06745687
- Acronym / sponsor ID
- IIT2024009
- Conditions
- High Risk Smoldering Multiple Myeloma
- Keywords
- high risk smoldering multiple myeloma, BCMA/CD3 BiTE, CM-336
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Institute of Hematology & Blood Diseases Hospital, ChinaUniversity, hospital or other
- Collaborators
- Keymed Biosciences Co.Ltd
- Study start
- 30 Dec 2024 (actual)
- Primary completion
- 1 Aug 2027 (estimated)
- Study completion
- 1 Aug 2029 (estimated)
- First posted
- 20 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety and efficacy of CM-336, which is a BCMA/CD3 BiTE, in the treatment of high risk smoldering multiple myeloma.
Detailed description
The purpose of this study is to evaluate the safety and efficacy of CM-336, which is a BCMA/CD3 BiTE, in the treatment of high risk smoldering multiple myeloma.
High-risk SMM has a high risk of transforming to MM, and there is no unified treatment plan in clinical practice at present. Studies have proved that early treatment can help prevent end organ damage caused by disease progression and improve patient prognosis. The treatment of high-risk SMM needs to be further explored. BCMA/CD3 BITE in the treatment of RRMM shows a high remission rate and low toxicity and side effects, and it is expected to become a potential treatment choice for high-risk SMM patients
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- A single-arm multi-center trial
| Arm | Type | Receives |
|---|---|---|
| CM-336( BCMA/CD3 bispecific antibody) | Experimental | Drug: CM336Patients enrolled in the trial will receive CM336 subcutaneously, which is an BCMA/CD3 bispecific antibody therapy. |
Who may qualify
- Ages
- 18 to 78 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- Know and voluntarily sign an informed consent form (ICF).
- Age ≥18 years.
- Definite diagnosis of SMM: According to IMWG Criteria 10, the patient must have histologically or cytologically confirmed smoldering multiple myeloma (SMM), including:
- High-risk SMM are defined as meeting one or more of the three criteria in the following part: (i) Mayo 2018, (ii) IMWG 2020 and (iii) evolving pattern.
- (i)Mayo 2018
Key exclusion criteria (18 listed)
- Diagnosis of symptomatic multiple myeloma: refer to the Chinese Guidelines for Diagnosis and Treatment of multiple myeloma (revised in 2022);
- Along with other tumors that must be treated.
- Previously received immunotherapy against BCMA targets.
- The researchers judged that BCMA/CD 3 dual antibody therapy is not suitable, such as severe cardiopulmonary disease and other conditions that are not suitable for BCMA/CD 3 dual antibody therapy.
- Received SMM treatment within six months.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CM336Patients received subcutaneous CM-336 80 mg once weekly in 28-d cycles after two step-up priming doses of 3 mg and 20 mg given on day 1 and day 4 of cycle 1 and cycle2. Then patients will be given 160mg every 2 weeks from cycle 3 to cycle 6. The dosing interval is adjusted according to the evaluation of efficacy every 6 cycles from cycle 7 to cycle 24. | Drug | CM-336( BCMA/CD3 bispecific antibody) |
Primary outcome
minimal residual disease netativity(MRD negativity)
Time frame: baseline, 28 days per cycle, cycle 6 day 28, cycle 12 day 28, cycle 18 day 28, cycle 24 day 28, 1 year and 2 year after end of treatment.
The proportion of abnormal plasma cells occupying nuclear cells in the samples
6 secondary outcomes
time to response
Time frame: up to 2 years
Hematologic response rate
Time frame: up to 2 years
Adverse events and serious adverse events
Time frame: up to 2 years
progression free survival(PFS)
Time frame: up to 2 years after end of therapy
overall survival(OS)
Time frame: up to 2 years after end of therapy.
duration of response(DOR)
Time frame: up to 2 years after end of therapy
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2026.
Related trials for High Risk Smoldering Multiple Myeloma
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RecruitingPhase 2
Isatuximab and Iberdomide as Immunotherapy for High Risk in Smouldering Myeloma
Smouldering Myeloma
Active, not recruitingPhase 2
Isatuximab With or Without Lenalidomide in Patients With High Risk Smoldering Multiple Myeloma (ISAMAR)
Smoldering Plasma Cell Myeloma
Active, not recruitingPhase 3
Lenalidomide or Observation in Treating Patients With Asymptomatic High-Risk Smoldering Multiple Myeloma
Light Chain Deposition Disease, Smoldering Multiple Myeloma
RecruitingPhase 1
A Study of JNJ-79635322 in Combination With Daratumumab With or Without Lenalidomide for Multiple Myeloma, Newly Diagnosed AL Amyloidosis, and High-risk Smoldering Multiple Myeloma or JNJ-79635322 in Combination With Pomalidomide for Multiple Myeloma
Multiple Myeloma, Smoldering Multiple Myeloma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CM336 in people with High Risk Smoldering Multiple Myeloma, run by Institute of Hematology & Blood Diseases Hospital, China at 1 site in China.
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 29 inclusion and 18 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: looking for participants now, as of the sponsor's last update on 23 Jul 2026. 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 China. 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.
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?
Contact Gang An, MD, PhD (+86 022-23909171, angang@ihcams.ac.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
minimal residual disease netativity(MRD negativity) (time frame: baseline, 28 days per cycle, cycle 6 day 28, cycle 12 day 28, cycle 18 day 28, cycle 24 day 28, 1 year and 2 year after end of treatment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Jul 2026.