Recruiting
Phase 2

Daratumumab

Sponsor:

Mayo Clinic

Code:

NCT05898646

Conditions

AL Amyloidosis

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Bone Marrow Aspiration

Daratumumab

Echocardiography Test

Questionnaire Administration

X-Ray Imaging

Study Details

Brief summary:

This phase II trial compares shorter-duration versus longer-duration maintenance therapy with daratumumab for improving survival in patients who have received initial treatment with daratumumab for light chain (AL) amyloidosis. Maintenance therapy is treatment that is given to help keep cancer from coming back after it has disappeared following initial therapy. Daratumumab is in a class of medications called monoclonal antibodies. It binds to a protein called CD38, which is found on some types of immune cells and cancer cells, including myeloma cells. Daratumumab may block CD38 and help the immune system kill cancer cells. Daratumumab is commonly prescribed as initial treatment for patients with AL amyloidosis. However, it is not known what role daratumumab may play in the maintenance therapy period of patients with AL amyloidosis. This phase II trial compares shorter duration maintenance to longer duration maintenance for improving survival in patients with AL amyloidosis.

Conditions

AL Amyloidosis

Study ID

NCT05898646

Start date

Jul 17, 2023

Status verified date

Mar, 2026

Completion date

Nov 30, 2026

Anticipated

Primary completion date

Nov 30, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Age >= 18 years
  • Histological confirmation of AL amyloidosis with adequate typing (mass spectrometry, immunohistochemistry, immunofluorescence, immunogold)
  • AL amyloidosis with organ disease requiring therapy

  • NOTE: Disease requiring therapy is referred to the time of diagnosis. There are no limitations in baseline measurable disease parameters
  • Patients must have monoclonal protein studies (serum free light chain assay, serum immunofixation or serum MASS-FIX) obtained at time of diagnosis before induction therapy initiated and available for review to be enrolled.

  • NOTE: Patients are allowed to participate in this study if urine electrophoresis immunofixation study was not done at time of diagnosis or cannot be obtained
  • Patients must have completed 6 cycles of daratumumab (Dara)-CyBorD-based induction treatment prior to registration or have a plan to complete cycle 6 prior to cycle 1 day 1. NOTE: treatment in the study is allowed only after the completion of 6 cycles of induction
  • Patients must have achieved a hematological complete response (CR) (irrespective of organ response achievement) or hematological very good partial response (VGPR) (irrespective of organ response achievement) or hematological low-difference in involved and uninvolved free light chain (dFLC) partial response (PR) (irrespective of organ response achievement) or hematological PR with at least one organ response after receiving Dara-CyBorD-based induction.

  • NOTE: Patients with baseline dFLC < 5 mg/dL, must have achieved hematological CR, or dFLC < 1 mg/dL or achieved organ response prior to randomization
  • Patients in whom bortezomib and/or cyclophosphamide were omitted from induction due to toxicity concerns or adverse effects are allowed. Patients must receive at least daratumumab and dexamethasone at induction to qualify for the study

  • NOTE: Dexamethasone use does not need to be carried to end of induction for eligibility consideration
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, 2 or 3
  • Hemoglobin >= 8.0 g/dL (obtained =< 28 days prior to registration)
  • Absolute neutrophil count (ANC) >= 1000/mm\^3 (obtained =< 28 days prior to registration)
  • Platelet count >= 50,000/mm\^3 (obtained =< 28 days prior to registration)
  • Negative pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only.

  • NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Provide written informed consent

  • NOTE: Informed consent required =< 90 days prior registration
  • Ability to complete questionnaire(s) by themselves or with assistance
  • Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)

Exclusion Criteria:

  • Any of the following because this study involves an agent that has possible genotoxic, mutagenic and teratogenic effects:

  • Pregnant persons
  • Nursing persons
  • Persons of childbearing potential (and persons able to father a child) who are unwilling to employ adequate contraception
  • Received >1 cycle of daratumumab maintenance after end of induction therapy and prior to registration
  • Multiple myeloma at time of diagnosis as defined by any of the following:

  • Hypercalcemia: Serum calcium > 1 mg/dL higher than upper limit of normal or > 11 mg/dL
  • Renal insufficiency: Creatinine clearance < 40 mL per min or serum creatinine > 2 mg/dL attributed to high circulating light chains (i.e. cast nephropathy) or hypercalcemia
  • Anemia: Hemoglobin > 2 g/dL below lower limit of normal, or < 10 g/dL, attributed to high marrow myeloma infiltration
  • Bone lesions: >= 1 osteolytic lesion on skeletal x-ray, computed tomography (CT), or positron emission tomography (PET)-CT (bone imaging is not mandatory but based on clinical suspicion)
  • Clonal bone marrow plasma cells >= 60%
  • > 1 focal lesion on magnetic resonance imaging (MRI) (MRI is not mandatory but based on clinical suspicion)
  • If bone imaging (CT, MRI, PET-CT) was not done at time of diagnosis it is not needed to be performed at registration to rule out bone disease

  • >= 40% BMPCs irrespective of the above
  • The study will allow patients with involved: uninvolved serum-free light chain (sFLC) ratio >= 100 if this is the only criteria that defines amyloidosis if all the above criteria are not met
  • Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Note: Subjects with resolved infection (i.e., 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) deoxyribonucleic acid (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
  • Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy.

  • NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
  • Uncontrolled intercurrent illness including, but not limited to:

  • Ongoing or active infection
  • Unstable angina pectoris
  • Psychiatric illness/social situations that would limit compliance with study requirements

Study Design

Enrollment

96 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm I (6 cycles of daratumumab)

Patients receive daratumumab subcutaneously (SC) on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity for up to 6 cycles on study. Patients also undergo x-ray imaging at screening and undergo bone marrow aspiration, blood sample collection, and optional bone marrow biopsy throughout the study. Patients with cardiac involvement also undergo echocardiography throughout the trial.

active comparator: Arm II (18 cycles of daratumumab)

Patients receive daratumumab SC on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity for up to 18 cycles on study. Patients also undergo x-ray imaging at screening and undergo bone marrow aspiration, blood sample collection, and optional bone marrow biopsy throughout the study. Patients with cardiac involvement also undergo echocardiography throughout the trial.

Interventions

Bone Marrow Aspiration

Undergo bone marrow aspiration

Daratumumab

Given SC

Echocardiography Test

Undergo echocardiography

Questionnaire Administration

Ancillary studies

X-Ray Imaging

Undergo x-ray imaging

Biospecimen Collection

Undergo blood sample collection

Primary outcome measure

  • Event free survival [ Time Frame: From registration up to 36 months ]

Central Contacts and Locations

Central contacts

Clinical Trials Referral Office

855-776-0015mayocliniccancerstudies@mayo.edu

Locations

Mayo Clinic in Arizona

Recruiting

Scottsdale, Arizona, United States, 85259

Contacts

Clincal Trials Referral Office

855-776-0015mayocliniccancerstudies@mayo.edu

Principal Investigator:

Udit Yadav, MBBS

Mayo Clinic in Rochester

Recruiting

Rochester, Minnesota, United States, 55905

Contacts

Clinical Trials Referral Office

855-776-0015mayocliniccancerstudies@mayo.edu

Principal Investigator:

Taxiarchis Kourelis, MD

More Information

Sponsor

Mayo Clinic

Last update posted

Mar 30, 2026

Last verified

Mar, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Mayo Clinic on 2026-03-30.