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

NCT06455748 | Recruiting DMC

• 1 other identifier: Poma-DD-AL-01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Amyloid Light-chain Amyloidosis

Outcome Measures

Primary Outcomes (1)

• Hematologic Overall Remission Rate (ORR)

  ORR was defined as the proportion of subjects who achieved partial remission (PR) or better partial remission (VGPR) and complete response (CR) by Guideline 2021 Edition criteria.

  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 (7)

• Hematologic complete remission (CR) rate

  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.

• Very good partial remission (VGPR) rate

  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.

• Overall survival (OS)

  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.

• Progression free survival （PFS）

  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.

• Negative rate of microscopic residual disease (MRD)

  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 (2)

• Adverse event

  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.

• EORTC QLQ-C30

  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.

Study Arms (1)

Daratumumab/daratumumab and hyaluronidase-fihj in combination with pomalidomide, dexamethasone (DPd)

EXPERIMENTAL

Observed patients meeting the screening criteria were treated with Daratumumab/daratumumab and hyaluronidase-fihj + pomalidomide + dexamethasone regimen as appropriate. Combined regimen of the above until disease progression or up to 2 years.

Drug: Daratumumab/daratumumab and hyaluronidase-fihj; Drug: Pomalidomide; Drug: Dexamethasone

Interventions

Daratumumab/daratumumab and hyaluronidase-fihj DRUG

Daratumumab/daratumumab and hyaluronidase-fihj: Dara SC 1800mg subcutaneous (IH) or Dara 16mg/kg intravenously (IV) administered weekly (qwk) x 4 every 2 weeks X 3 doses per month starting C7.

Also known as: Dara

Daratumumab/daratumumab and hyaluronidase-fihj in combination with pomalidomide, dexamethasone (DPd)

Pomalidomide DRUG

Pomalidomide: pom 2-4mg PO day (D) 1-21/28 (adjust dose for renal function).

Also known as: pom

Daratumumab/daratumumab and hyaluronidase-fihj in combination with pomalidomide, dexamethasone (DPd)

Dexamethasone DRUG

Dexamethasone: dex C1: 20mg IV D1/8, 20mg PO D2/9 and 40mg PO C1D15 weekly up to C6, then 20mg IV monthly starting C7D1 and 20mg PO D8, 15, 22.

Also known as: dex

Daratumumab/daratumumab and hyaluronidase-fihj in combination with pomalidomide, dexamethasone (DPd)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 18-80 years old, diagnosed with primary amyloidosis of AL tissue;
• ECOG PS score 0-2 points;
• Measurable disease: The difference between affected and unaffected FLC is\>20 mg/L, and the serum immunoglobulin kappa λ FLC ratio is abnormal;
• Having sufficient organ and bone marrow function, defined as follows:
• Blood routine: Absolute neutrophil count ≥ 1.0 x 10 \^ 9/L, platelet count ≥ 50 x 10 \^ 9/L;
• 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);
• 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;
• Men must agree to use contraceptive measures during the study period and within 3 months after the end of the study period;
• The patient agrees to participate in the clinical trial and signs an informed consent form.

You may not qualify if:

• Non AL amyloidosis;
• 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;
• Female patients who have tested positive for lactation or serum pregnancy test during the screening period;
• Received ASCT or had graft-versus-host disease in the past 12 months;
• Suffering from moderate or severe persistent asthma within 2 years prior to enrollment, or having uncontrolled asthma at the time of enrollment;
• 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;
• Suffering from chronic obstructive pulmonary disease (COPD), the forced expiratory volume (FEV1) in one second is less than 50% of the normal expected value;
• Clinically significant heart disease, including:
• 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);
• Arrhythmias (NCI CTCAE V5.0 standard ≥ grade 3) or clinically significant electrocardiogram (ECG) abnormalities;
• The electrocardiogram shows a baseline corrected QT (QTc) interval\>470 ms;
• Active infections, including but not limited to HAV, HBV, HCV, HIV;
• 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);
• Peripheral neuropathy or neuralgia of grade 2 or above (CTCAE 5.0 standard);
• 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);

Sponsors & Collaborators

• Yongyong MA: lead

Study Sites (1)

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, 325000, China

RECRUITING

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis

Interventions

daratumumab; darlin protein, Dictyostelium; pomalidomide; Dexamethasone

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

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Yongyong Ma, MD

  First Affiliated Hospital of Wenzhou Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yongyong Ma, MD

CONTACT

+86-13566281793; mayy@wmu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Physician of Hematology Department

Study Record Dates

• First Submitted: June 6, 2024
• First Posted: June 12, 2024
• Study Start: March 1, 2024
• Primary Completion: January 1, 2025
• Study Completion: March 1, 2025
• Last Updated: June 12, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)