Comparing Dara-VCD Chemotherapy Plus Stem Cell Transplant to Dara-VCD Chemotherapy Alone for People Who Have Newly Diagnosed AL Amyloidosis

Conditions

• AL Amyloidosis

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Autologous Hematopoietic Stem Cell Transplantation — PROCEDURE
  Given IV
• Biopsy — PROCEDURE
  Undergo fat pad biopsy
• Biospecimen Collection — PROCEDURE
  Undergo blood and urine specimen collection
• Bone Marrow Aspiration — PROCEDURE
  Undergo bone marrow aspiration
• Bone Marrow Biopsy — PROCEDURE
  Undergo bone marrow biopsy
• Bortezomib — DRUG
  Given SC
• Computed Tomography — PROCEDURE
  Undergo CT scan
• Cyclophosphamide — DRUG
  Given PO or IV
• Daratumumab and Hyaluronidase-fihj — DRUG
  Given SC
• Dexamethasone — DRUG
  Given PO or IV
• Echocardiography — PROCEDURE
  Undergo echocardiography
• Magnetic Resonance Imaging — PROCEDURE
  Undergo MRI
• Melphalan — DRUG
  Given IV
• Positron Emission Tomography — PROCEDURE
  Undergo PET-CT
• Stem Cell Isolation — PROCEDURE
  Undergo stem cell collection
• Survey Administration — OTHER
  Ancillary study

Study Details

This phase III trial compares the effect of adding a stem cell transplant with melphalan after completing chemotherapy with daratumumab, cyclophosphamide, bortezomib and dexamethasone (Dara-VCD) versus chemotherapy with Dara-VCD alone for treating patients with newly diagnosed amyloid light chain (AL) amyloidosis. Melphalan is a chemotherapy given prior to a stem cell transplant. Giving chemotherapy before a peripheral blood stem cell transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. The stem cells are then returned to the patients to replace the blood forming cells that were destroyed by the chemotherapy. 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. Chemotherapy drugs, such as cyclophosphamide and bortezomib, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Dexamethasone is in a class of medications called corticosteroids. It is used to lower the body's immune response to help stop the growth of cancer cells. Giving a stem cell transplant with melphalan after Dara-VCD may kill more cancer cells in patients with newly diagnosed AL amyloidosis.

Key Dates

Start date

Jul 1, 2024

Status verified

Sep 2025

Primary completion

Jul 29, 2030

Completion

Oct 29, 2030

Study Design

Enrollment

338 participants (estimated)

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Active Comparator: Consolidation Arm I (Chemotherapy)
  Patients receive daratumumab and hyaluronidase-fihj SC over 3-5 minutes on days 1 and 15 as well as bortezomib SC over 3-5 minutes, cyclophosphamide PO or IV, and dexamethasone PO or IV on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography at screening and at progression. Patients undergo bone marrow aspiration and biopsy within14-28 days post consolidation treatment and at progression. Patients undergo blood and urine sample collection at screening, at the start of each cycle, and the end of treatment and during follow up or at progression.
• Experimental: Consolidation Arm II (Chemotherapy, ASCT)
  Patients undergo collection of peripheral blood stem cells. Patients receive melphalan IV for 1 cycle and then 2 days later receive the stem cell transplant IV in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography at screening and at progression. Patients undergo bone marrow aspiration and biopsy within 60-90 days post initiation of stem cell transplant. Patients undergo blood and urine sample collection at screening, during treatment, and the end of treatment and during follow up or at progression.
• Experimental: Induction (Chemotherapy)
  Patients receive daratumumab and hyaluronidase-fihj SC over 3-5 minutes on days 1, 8, 15 and 22 for 2 cycles and then days 1 and 15 for cycle 3. Patients receive bortezomib SC over 3-5 minutes, cyclophosphamide PO or IV, and dexamethasone PO or IV on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI or PET-CT and fat pad aspiration at screening. Patients undergo echocardiography at screening, the completion of induction, and at progression. Patients undergo bone marrow aspiration and biopsy at screening, post induction treatment and at progression. Patients undergo blood and urine sample collection at screening, at the start of each cycle, and the end of treatment and during follow up or at progression.
• Experimental: Maintenance (daratumumab and hyaluronidase-fihj)
  Patients receive maintenance daratumumab and hyaluronidase-fihj SC over 3-5 minutes on day 1 of each cycle. Cycles repeat every 28 days for up 18 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography at screening, 12 months post consolidation treatment and at progression. Patients undergo bone marrow aspiration and biopsy 12 months post consolidation treatment and at progression. Patients undergo blood and urine sample collection at screening, during treatment, 12 months post consolidation treatment and during follow up or at progression.

Primary Outcome Measure

Major organ deterioration progression-free survival (PFS) [ Time Frame: From date of randomization (Step 2 registration) to date of first documentation of hematologic progression, cardiac organ progression, renal organ progression, or death due to any cause, assessed up to 4 years ]

Locations (117)

Find similar trials in Goodyear, AZ

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