Clinical Trials

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 Dara-CyBorD-based induction treatment ≤84 days prior to registration.
• Patients must have achieved a hematological CR (irrespective of organ response achievement) or hematological VGPR (irrespective of organ response           achievement) or hematological low-dFLC 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.
• ECOG Performance Status (PS) 0, 1, 2 or 3. 
• The following laboratory values obtained ≤28 days prior to registration:
  • Hemoglobin ≥ 8.0 g/dL;
  • Absolute neutrophil count (ANC) ≥1000/mm^3;
  • Platelet count ≥ 50,000/mm^3.
• 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, CT, or PET-CT (bone imaging is not mandatory but based on clinical suspicion);
  • Clonal bone marrow plasma cells ≥ 60%;
  • >1 focal lesion on 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 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) 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 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.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 12/5/23.   Questions regarding updates should be directed to the study team contact.