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

Institute of Hematology & Blood Diseases Hospital, China

Status

Not yet enrolling

Conditions

AL Amyloidosis

Treatments

Drug: CM-336 BCMA/CD3 bispecific antibody

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT06769555

IIT2024012

Details and patient eligibility

About

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.

Full description

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).

Enrollment

20 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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
Platelet count ≥75,000/µL
Hemoglobin ≥75g/L
Total bilirubin ≤1.5× the upper limit of normal (ULN), except for patients with Gilbert's syndrome (as defined by >80% unconjugated bilirubin and total bilirubin ≤6 mg/dL)
Alkaline phosphatase ≤5× ULN
Alanine aminotransferase or aspartate aminotransferase ≤3× ULN
Calculated creatinine clearance ≥30 mL/min
The woman is not breastfeeding, is not pregnant, and agrees not to be pregnant during the study period and for the following 12 months.
Male patients agreed that their spouse would not become pregnant during the study period and for 12 months thereafter.

Exclusion criteria

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.