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

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

ClinicalTrials.gov ID: NCT06022939
Sponsor: SWOG Cancer Research Network
Information provided by: SWOG Cancer Research Network (Responsible Party)
Last Update Posted: 2023-09-05

Brief Summary:
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.

Detailed Description:
PRIMARY OBJECTIVE:
I. To compare major organ deterioration progression-free survival between participants randomized to the autologous stem cell transplant (ASCT) and non-ASCT arms of this study.

SECONDARY OBJECTIVES:
I. To compare overall survival (OS) between participants randomized to the ASCT and non-ASCT arms of this study.

II. To compare rates of cardiac and renal organ responses between participants randomized to the ASCT and non-ASCT arms of this study.

III. To compare rates of cardiac and renal organ progression between participants randomized to the ASCT and non-ASCT arms of the study.

IV. To compare the frequency and severity of toxicities between participants randomized to the ASCT and non-ASCT arms of this study.

V. To compare minimal residual disease (MRD) negativity rates between participants randomized to the ASCT and non-ACST arms of this study.

ADDITIONAL OBJECTIVES:
I. To compare the best overall hematologic response rates between participants randomized to the ASCT and non-ASCT arms of this study.

II. To compare rates of hematologic complete response (CR) and very good partial response, following completion of consolidation therapy between participants randomized to the ASCT and non-ASCT arms of this study, post-consolidation.

III. To compare hematologic progression-free survival between participants randomized to the ASCT and non-ASCT arms of this study.

IV. To compare time to next treatment between participants randomized to the ASCT and non-ASCT arms of the study.

V. To evaluate utilization of delayed ASCT in participants randomized to the non-ASCT arm of the study.

TRANSLATIONAL MEDICINE PRIMARY OBJECTIVES:
I. To compare MRD negativity rates from bone marrow aspirates via next generation flow cytometry (NGF) between the ASCT and non-ASCT arms of this study post-consolidation.

II. To bank specimens for future use.

TRANSLATIONAL MEDICINE EXPLORATORY OBJECTIVES:
I. To evaluate MRD negativity rates at post-induction, and compare MRD negativity rates at 12 months post-consolidation from bone marrow aspirates via NGF between participants randomized to the ASCT and non-ASCT arms of this study.

II. To investigate the association of achieving MRD negativity at any point (post-induction, post-consolidation, or 12 months post-consolidation) via NGF from bone marrow aspirates with major organ deterioration-progression free survival (MOD-PFS).

III. To investigate the association of achieving sustained MRD negativity (MRD negative at two consecutive measurements -- post-induction, post-consolidation, and 12 months post-consolidation) via NGF from bone marrow aspirates with MOD-PFS.

QUALITY OF LIFE (QOL) PRIMARY OBJECTIVE:
I. To compare patient-reported physical function following consolidation treatment between participants randomized to the ASCT and non-ASCT arms using the Patient Reported Outcomes Measurement Information System (PROMIS)-29+2 Profile version (v) 2.1 physical function sub-scale.

QOL SECONDARY OBJECTIVES:
I. To compare patient-reported fatigue following consolidation treatment between participants randomized to the ASCT and non-ASCT arms using the PROMIS-29 fatigue subscale.

II. To compare longitudinal changes in physical function using the PROMS-29+2 between participants randomized to the ASCT and non-ASCT arms.

QOL EXPLORATORY OBJECTIVES:
I. To assess baseline symptom burden in AL amyloidosis patients prior to induction therapy using the PROMIS-29+2.

II. To compare mean scores of symptom scales using the PROMIS-29+2 following consolidation treatment, and at 6 months and 12 months from step 3 registration between treatment arms.

III. To compare mean scores of functional scales using the PROMIS-29+2, following consolidation treatment, and at 6 months and 12 months from step 3 registration between treatment arms.

IV. To explore whether longitudinal changes in symptoms, functioning, and overall heath related quality of life (HRQoL) as assessed by the PROMIS-29 +2 (version 2.1) differ according to treatment group and, separately, according to baseline cardiac or renal involvement using interaction tests between participants randomized to the ASCT and non-ASCT arms.

V. To compare health utility indices using the PROMIS preference score (PROPr) between patients randomized to the ASCT and non-ASCT arms.

PATIENT REPORTED OUTCOME (PRO)-COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS (CTCAE) PRIMARY OBJECTIVE:
I. To compare patient reported symptoms regarding treatment emergent adverse events of interest using the Patient Reported Outcome CTCAE (PRO-CTCAE) Measurement System between patients randomized to the ASCT and non-ASCT arms of this study.

OFFICIAL TITLE
A Phase III, Randomized Study of Daratumumab, Cyclophosphamide, Bortezomib and Dexamethasone (Dara-VCD) Induction Followed by Autologous Stem Cell Transplant or Dara-VCD Consolidation and Daratumumab Maintenance in Patients With Newly Diagnosed AL Amyloidosis

INTERVENTION / TREATMENT
Procedure: Autologous Hematopoietic Stem Cell Transplantation
Procedure: Biopsy
Procedure: Biospecimen Collection
Procedure: Bone Marrow Aspiration
Procedure: Bone Marrow Biopsy
Drug: Bortezomib
Procedure: Computed Tomography
Drug: Cyclophosphamide
Drug: Daratumumab and Hyaluronidase-fihj
Drug: Dexamethasone
Procedure: Echocardiography
Procedure: Magnetic Resonance Imaging
Drug: Melphalan
Procedure: Positron Emission Tomography
Procedure: Stem Cell Isolation
Other: Survey Administration

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