Clinical trial NCT06455748: Daratumumab/Daratumumab and Hyaluronidase-fihj in Combination With Pomalidomide and Dexamethasone for the Treatment of Patients With Newly Diagnosed AL Amyloidosis: a Prospective, Multicenter, Single-arm Study
Official title: Daratumumab/Daratumumab and Hyaluronidase-fihj in Combination With Pomalidomide and Dexamethasone for the Treatment of Patients With Newly Diagnosed AL Amyloidosis: a Prospective, Multicenter, Single-arm Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Amyloid Light-chain Amyloidosis
Lead sponsor: First Affiliated Hospital of Wenzhou Medical University
Sponsor class: OTHER
First posted: 2024-06-12
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a prospective and single arm clinical study. The goal of this clinical trial is to observe and evaluate the efficacy and safety of Daratumumab/daratumumab and hyaluronidase-fihj in combination with pomalidomide and dexamethasone in the treatment of patients with newly diagnosed AL amyloidosis.

Detailed description: Primary objective:

Hematologic overall remission rate (ORR) as defined by the criteria in the Chinese Guidelines for the Diagnosis and Treatment of Systemic Light Chain Amyloidosis, 2021 edition.

Secondary objective:

1. organ remission rate as defined by the criteria of the Chinese Guidelines for the Diagnosis and Treatment of Systemic Light-Chain Amyloidosis 2021 Edition, hematologic complete remission (CR) rate, very good partial remission (VGPR) rate, progression free survival (PFS), overall survival (OS), and negative rate of microscopic residual disease (MRD).
2. safety of combination therapy regimens.

Exploratory purpose:

EORTC QLQ-C30.

Eligibility criteria: Inclusion Criteria:

1. Age: 18-80 years old, diagnosed with primary amyloidosis of AL tissue;
2. ECOG PS score 0-2 points;
3. Measurable disease: The difference between affected and unaffected FLC is\>20 mg/L, and the serum immunoglobulin kappa λ FLC ratio is abnormal;
4. Having sufficient organ and bone marrow function, defined as follows:

   1. Blood routine: Absolute neutrophil count ≥ 1.0 x 10 \^ 9/L, platelet count ≥ 50 x 10 \^ 9/L;
   2. Blood biochemistry and electrolytes: ALT and AST both ≤ 3 times the upper limit of normal, total bilirubin ≤ 1.5 times the upper limit of normal, creatinine clearance rate ≥ 30 mL/min, serum corrected calcium ≤ 14.0 mg/dL (≤ 3.5 mmol/L) or free ion calcium ≤ 6.5 mg/dL (≤ 1.6 mmol/L);
5. Women of childbearing age must agree to use contraceptive measures (such as intrauterine devices, contraceptives, or condoms) during the study period and within 3 months after the end of the study; Within 7 days prior to enrollment in the study, the serum or urine pregnancy test was negative and must be a non lactating patient; In addition, if the subject misses their menstrual period or experiences abnormal menstrual bleeding, the researcher can conduct a pregnancy trial at any time during the study period;
6. Men must agree to use contraceptive measures during the study period and within 3 months after the end of the study period;
7. The patient agrees to participate in the clinical trial and signs an informed consent form.

Exclusion Criteria:

1. Non AL amyloidosis;
2. Known to be allergic, hypersensitive or intolerant to monoclonal antibodies or human derived proteins, daretozumab or its excipients, or known to be allergic to mammalian derivatives;
3. Female patients who have tested positive for lactation or serum pregnancy test during the screening period;
4. Received ASCT or had graft-versus-host disease in the past 12 months;
5. Suffering from moderate or severe persistent asthma within 2 years prior to enrollment, or having uncontrolled asthma at the time of enrollment;
6. Evidence of having other malignant tumors within the 3 years prior to enrollment or having been previously diagnosed with another malignant tumor with any residual lesions;
7. Suffering from chronic obstructive pulmonary disease (COPD), the forced expiratory volume (FEV1) in one second is less than 50% of the normal expected value;
8. Clinically significant heart disease, including:

   1. Start studying myocardial infarction or unstable or uncontrollable conditions within 6 months prior to treatment (such as unstable angina, congestive heart failure, New York Heart Association (NYHA) III-IV);
   2. Arrhythmias (NCI CTCAE V5.0 standard ≥ grade 3) or clinically significant electrocardiogram (ECG) abnormalities;
   3. The electrocardiogram shows a baseline corrected QT (QTc) interval\>470 ms;
9. Active infections, including but not limited to HAV, HBV, HCV, HIV;
10. Plasma cell leukemia (circulating plasma cells\>2.0 × 10 \^ 9/L) or Waldenstrom macroglobulinemia (WM) or POEMS syndrome (multiple neuropathies, organ enlargement, endocrine disorders, monoclonal plasma cell disease, and skin changes);
11. Peripheral neuropathy or neuralgia of grade 2 or above (CTCAE 5.0 standard);
12. Underwent major surgery within 14 days prior to enrollment, or did not fully recover from early surgery, or planned surgery during the study period or within 14 days after the last study drug treatment (note: does not include surgery under local anesthesia or kyphoplasty or vertebroplasty);
13. According to the judgment of the investigator, there are concomitant diseases (such as active systemic infection, uncontrolled diabetes, acute diffuse invasive pulmonary disease, neurological or mental disease, etc.) or any other conditions that may confuse the research results or affect the completion of the study;
14. Individuals who are receiving any other experimental drugs or experimental medical devices;
15. The researchers believe that the patient has other circumstances that are not suitable for participation in this study.

Primary outcomes:
measure: Hematologic Overall Remission Rate (ORR)
timeFrame: A follow-up is required 30 days (± 7 days) after the completion of all treatments, followed by a follow-up every 12 weeks (± 7 days) for a period of 1 year.
Secondary outcomes:
measure: Hematologic complete remission (CR) rate
timeFrame: A follow-up is required 30 days (± 7 days) after the completion of all treatments, followed by a follow-up every 12 weeks (± 7 days) for a period of 1 year.
measure: Very good partial remission (VGPR) rate
timeFrame: A follow-up is required 30 days (± 7 days) after the completion of all treatments, followed by a follow-up every 12 weeks (± 7 days) for a period of 1 year.
measure: Overall survival (OS)
timeFrame: A follow-up is required 30 days (± 7 days) after the completion of all treatments, followed by a follow-up every 12 weeks (± 7 days) for a period of 1 year.
measure: Progression free survival （PFS）
timeFrame: A follow-up is required 30 days (± 7 days) after the completion of all treatments, followed by a follow-up every 12 weeks (± 7 days) for a period of 1 year.
measure: Negative rate of microscopic residual disease (MRD)
timeFrame: A follow-up is required 30 days (± 7 days) after the completion of all treatments, followed by a follow-up every 12 weeks (± 7 days) for a period of 1 year.
measure: Time to response (TTR)
timeFrame: A follow-up is required 30 days (± 7 days) after the completion of all treatments, followed by a follow-up every 12 weeks (± 7 days) for a period of 1 year.
measure: Duration of response (DOR)
timeFrame: A follow-up is required 30 days (± 7 days) after the completion of all treatments, followed by a follow-up every 12 weeks (± 7 days) for a period of 1 year.
Other outcomes:
measure: Adverse event
timeFrame: A follow-up is required 30 days (± 7 days) after the completion of all treatments, followed by a follow-up every 12 weeks (± 7 days) for a period of 1 year.
measure: EORTC QLQ-C30
timeFrame: A follow-up is required 30 days (± 7 days) after the completion of all treatments, followed by a follow-up every 12 weeks (± 7 days) for a period of 1 year.
Locations:
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
affiliation: First Affiliated Hospital of Wenzhou Medical University
name: Yongyong Ma, MD
role: PRINCIPAL_INVESTIGATOR
References: