BCMA/CD3 BiTE for RRAL or NDAL Amyloidosis With Insufficient Depth of Hematologic Response After Induction Therapy

NCT06769555 | Withdrawn

• 1 other identifier: IIT2024012
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to evaluate the effectiveness and safety of CM-336, which is a BCMA/CD3 BiTE, in patients with relapsed/refractory AL amyloidosis or newly diagnosed AL amyloidosis with insufficient depth of hematologic response after induction therapy.

Conditions

AL Amyloidosis

Keywords

AL Amyloidosis; BCMA/CD3 BiTE; CM-336

Outcome Measures

Primary Outcomes (2)

• Hematologic response VGPR or better rate after four cycles

  Hematologic response VGPR or better rate based on central laboratory results and the 2010 International Society of Amyloidosis (ISA) Consensus Criteria as evaluated by an Adjudication Committee (AC)

  Four months

• Adverse events and serious adverse events

  Adverse events (AEs), serious adverse events (SAEs), according to Common Terminology Criteria for Adverse Events (CTCAE) 5.0

  Up to 2 year

Secondary Outcomes (8)

• Time to hematologic response

  Up to 2 year

• Hematologic best response

  Up to 2 year

• Duration of hematologic response

  Up to 2 year

• Hematologic response rate

  Up to 2 year

• Overall survival

  Up to 5 year

Study Arms (1)

BCMA/CD3 BiTE

EXPERIMENTAL

Drug: CM-336 BCMA/CD3 bispecific antibody

Interventions

CM-336 BCMA/CD3 bispecific antibody DRUG

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. For patients achieve hematological PR or better after 2 cycles, and hematological VGPR or better after 4 cycles, the treatment regimen will change to 160mg once every 2 weeks (Q2W).

BCMA/CD3 BiTE

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged 18 years or older
• Biopsy-proven diagnosis of AL amyloidosis, according to the following standard criteria:
• Histochemical diagnosis of amyloidosis, as based on tissue specimens with Congo red staining with exhibition of an apple-green birefringence
• If clinical and laboratory parameters are insufficient to establish AL amyloidosis, or in cases of doubt, amyloid typing may be necessary
• Provide informed consent form
• Measurable disease, as defined by serum differential free light-chain concentration (dFLC; defined as the difference between amyloid forming \[involved\] and nonamyloid forming \[uninvolved\] free light-chain \[FLC\]) ≥50 mg/L)
• Received at least one prior line of therapy
• Must have been exposed to CD38 mAb
• Relapsed/refractory AL amyloidosis or newly diagnosed AL amyloidosis with insufficient depth of hematologic response after induction therapy
• Relapsed is defined as documented progressive disease \>60 days after the last dose of prior therapy
• Refractory is defined as the documented absence of a hematologic response or hematologic progression on or within 60 days after the last dose of prior therapy
• Insufficient depth of hematologic response is defined as less than hematological PR by 2 cycles or less than hematologic VGPR by 4 cycles
• Eastern Cooperative Oncology Group performance status ≤3
• Clinical laboratory values:
• Absolute neutrophil count ≥1000/µL

You may not qualify if:

• Non-AL amyloidosis, including hereditary amyloidosis
• Diagnosed with multiple myeloma, according to the International Myeloma Working Group criteria
• Have been exposed to BCMA-targeted treatment
• Known intolerance, hypersensitivity, or contraindication to BCMA BiTE cellular products
• Patients with peripheral neuropathy greater than grade 2 or peripheral neuropathy greater than grade 2 with pain at baseline, regardless of whether they were currently receiving medical therapy, after excluding AL amyloidosis-related peripheral neuropathy
• Medically documented cardiac syncope, myocardial infarction within the previous 6 months, unstable angina pectoris, clinically significant repetitive ventricular arrhythmias despite antiarrhythmic treatment, or severe orthostatic hypotension or clinically important autonomic disease
• Ongoing or active infection, known HIV-positive status, or active hepatitis B or C infection
• Women who are pregnant or breastfeeding
• Subjects had major surgery within 2 weeks before randomization (for example, general anesthesia), or have not fully recovered from the surgery, or surgery is arranged during the study period
• Received live attenuated vaccine within 4 weeks prior to study treatment
• According to the researcher's judgment, any condition including but not limited to serious mental illness, medical illness, or other symptoms/conditions that may affect study treatment, compliance, or the capability of providing informed consent.
• Necessary medication or supportive therapy is contraindicated with study treatment.
• Any diseases or complications that may interfere with the study. Patients are not willing to or cannot comply with study scheme.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead
• Keymed Biosciences Co.Ltd: collaborator

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A single-arm multi-center trial

Study Record Dates

• First Submitted: December 10, 2024
• First Posted: January 10, 2025
• Study Start: January 1, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2028
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share