Daratumumab and Pomalidomide in Previously Treated Patients With AL Amyloidosis

NCT04895917 | Terminated Phase 2

• 1 other identifier: AC-016-IT
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 3

Brief Summary

This study aims at establishing a new powerful combination of daratumumab and pomalidomide as rescue treatment for patients with R/R AL amyloidosis.

Conditions

AL Amyloidosis

Keywords

AL Amyloidosis; Daratumumab; Pomalidomide; relapsed/refractory AL Amyloidosis

Outcome Measures

Primary Outcomes (1)

• Rate of good quality (i.e. CR+VGPR) hematologic response.

  To assess the rate of good quality (i.e. CR+VGPR) hematologic response at the completion of 6 cycles of Daratumumab plus pomalidomide in patients with relapsed/refractory AL amyloidosis not in VGPR or better after any previous therapy.

  6 months

Secondary Outcomes (9)

• To assess in all patients according to their disease history the overall Hematologic Response Rate (CR, VGPR, LowdFLC partial response and PR) at the completion of 1st and 3rd cycles.

  At the end of Cycle 1 and Cycle 3 (each cycle is 28 days)

• To assess in all patients the overall Hematologic Response Rate including PR at the completion of 6 cycles.

  6 months

• To assess in all patients duration of hematologic response. After treatment discontinuation, follow-up will be made to the patient every 3 months for at least 1 year.

  1 year after treatment discontinuation

• To assess in all patients the rate of organ response (i.e. cardiac response: NT-proBNB measurement; renal response: proteinuria measurement) and organ improvement, according to standard criteria (Palladini et al JCO 2012, Palladini et al Blood 2014).

  6 months

• To assess in all patients the time from the screening to hematologic and organ response.

  6 months

Study Arms (1)

Pomalidomide and daratumumab

EXPERIMENTAL

Drug: daratumumab and pomalidomide

Interventions

daratumumab and pomalidomide DRUG

Patient eligible to enter the study will receive 6 cycles of 28 days of subcutaneous Daratumumab (1800 mg SC) and oral pomalidomide 4 mg from day 1 to day 21. During cycle 1 and 2, Daratumumab will be administered weekly at days 1, 8, 15, and 22 then from cycle 3 to 6, Daratumumab will be administered every other week at days 1 and 15.

Pomalidomide and daratumumab

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologic diagnosis of AL amyloidosis;
• Measurable hematologic disease: difference between involved and uninvolved FLC \> 20 mg/L with an abnormal k/l ratio;
• Symptomatic organ involvement (heart, kidney, liver/GI tract, peripheral nervous system);
• Wash-out period of at least 4 weeks from previous antitumor therapy or any investigational treatment or 5 half-lives from previous antibodies, whichever is longer. Treatment from previous therapy should be in accordance to the local clinical practice in which a 4 weeks period is required for the evaluation of response;
• Adequate bone marrow function prior to 1st drug intake (C1D1), without transfusion or growth factor support within 5 days prior to 1st drug intake, defined as:
• Absolute neutrophils ≥ 1000/mm3,
• Platelets ≥ 50000/mm3,
• Hemoglobin ≥ 9.0 g/dL,
• Adequate organ function defined as:
• Serum SGOT/AST or SGPT/ALT \< 3.0 X Upper Limit of the normal range (ULN),
• Serum total bilirubin level\<1.5x ULN, unless for subjects with Gilbert's syndrome where the direct bilirubin should then be ≤2.0 x ULN.
• Female patients who are postmenopausal for at least 1 year before the screening visit, or are surgically sterile, or if they are of childbearing potential, agree to practice effective methods of contraception from the time of signing the informed consent through 30 days after the last dose of study drug, or agree to completely abstain from intercourse (serum pregnancy test has to be performed for all women of childbearing potential at the beginning of each cycle during the study. In addition, a pregnancy test may be done at any time during the study at the discretion of the investigator if a subject miss a period or has unusual menstrual bleeding);
• Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.

You may not qualify if:

• Presence of non-AL amyloidosis;
• AL amyloidosis with isolated soft tissue involvement;
• Bone marrow plasma cells \>30% and clinically symptomatic multiple myeloma with lytic bone lesions;
• NT-proBNP \>8500 ng/L and hs-troponin I \>100 ng/L (cardiac stage IIIb patients);
• Repetitive ventricular arrhythmias on 24h Holter ECG despite anti-arrhythmic treatment, except if a pacemaker has been implanted;
• Chronic atrial fibrillation with uncontrolled heart rate;
• Supine systolic blood pressure \<100 mmHg;
• Subject is a woman who is pregnant, or breast-feeding, or planning to become pregnant;
• Subjects with known chronic obstructive pulmonary disease or persistent asthma ;
• Previous anti-CD38 or pomalidomide therapy;
• Presence of other active malignancy with the exception of non-melanoma skin cancer, cervical cancer, treated early-stage prostate cancer provided that prostate specific antigen is within normal limit, or any completely resected carcinoma in situ;
• Subjects with known/underlying medical conditions that, in the investigator's opinion would make the administration of the study drug hazardous (ie: uncontrolled diabetes oruncontrolled coronary artery disease);
• Subject is:
• (Known to be) seropositive for human immunodeficiency virus (HIV)
• seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]).Subjects with resolved infection (ie, subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen \[anti-HBc\] and/or antibodies to hepatitis B surface antigen \[anti-HBs\]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti- HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.

Sponsors & Collaborators

• Fondazione IRCCS Policlinico San Matteo di Pavia: lead

Study Sites (3)

Policlinico Universitario "Mater Domini"

Catanzaro, Italy

Location

Foundation IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

Università Campus Biomedico

Rome, Italy

Location

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis

Interventions

daratumumab; pomalidomide

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: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 10, 2021
• First Posted: May 20, 2021
• Study Start: June 23, 2021
• Primary Completion: December 18, 2024
• Study Completion: January 15, 2025
• Last Updated: February 20, 2025

Record last verified: 2025-02

Locations

IT (3)