Comparing Dara-VCD Chemotherapy Plus Stem Cell Transplant to Dara-VCD Chemotherapy Alone for People Who Have Newly Diagnosed AL Amyloidosis
Start Date
7/1/2024
Completion Date
10/29/2030
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. OUTLINE: INDUCTION: Patients receive daratumumab and hyaluronidase-fihj subcutaneously (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 orally (PO) or intravenously (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 computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography (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. CONSOLIDATION: Patients who achieve an overall response of partial response or better after 3 cycles of Dara-VCD are randomized to 1 of 2 arms. ARM I: 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. ARM II: 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. MAINTENANCE: 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. After completion of study treatment, patients are followed up every 3 or 6 months up to 4 years after registration.
Eligibility Criteria
Age Range: 18 years to No maximum
Interventions
Autologous Hematopoietic Stem Cell Transplantation
Biopsy
Biospecimen Collection
Bone Marrow Aspiration
Bone Marrow Biopsy
Bortezomib
Computed Tomography
Cyclophosphamide
Daratumumab and Hyaluronidase-fihj
Dexamethasone
Echocardiography
Magnetic Resonance Imaging
Melphalan
Positron Emission Tomography
Stem Cell Isolation
Survey Administration
Conditions
Locations
CTCA at Western Regional Medical Center
Goodyear, Arizona 85338
United States
Banner University Medical Center - Tucson
Tucson, Arizona 85719
United States
University of Arizona Cancer Center-North Campus
Tucson, Arizona 85719
United States
City of Hope Comprehensive Cancer Center
Duarte, California 91010
United States
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California 92612
United States
City of Hope at Irvine Lennar
Irvine, California 92618
United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California 92868
United States
Smilow Cancer Hospital-Derby Care Center
Derby, Connecticut 06418
United States
Smilow Cancer Hospital Care Center at Greenwich
Greenwich, Connecticut 06830
United States
Smilow Cancer Hospital Care Center - Guilford
Guilford, Connecticut 06437
United States
Smilow Cancer Hospital Care Center at Saint Francis
Hartford, Connecticut 06105
United States
Yale University
New Haven, Connecticut 06520
United States
Yale-New Haven Hospital North Haven Medical Center
North Haven, Connecticut 06473
United States
Smilow Cancer Hospital Care Center at Long Ridge
Stamford, Connecticut 06902
United States
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut 06611
United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia 20007
United States
UM Sylvester Comprehensive Cancer Center at Aventura
Aventura, Florida 33180
United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida 33146
United States
UM Sylvester Comprehensive Cancer Center at Coral Springs
Coral Springs, Florida 33065
United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida 33442
United States
UM Sylvester Comprehensive Cancer Center at Hollywood
Hollywood, Florida 33021
United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida 33136
United States
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida 33176
United States
University of Miami Sylvester Comprehensive Cancer Center at Sole Mia
North Miami, Florida 33181
United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida 33324
United States
Emory University Hospital Midtown
Atlanta, Georgia 30308
United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia 30322
United States
Rush-Copley Medical Center
Aurora, Illinois 60504
United States
University of Illinois
Chicago, Illinois 60612
United States
Carle at The Riverfront
Danville, Illinois 61832
United States
Carle Physician Group-Effingham
Effingham, Illinois 62401
United States
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois 61938
United States
Loyola University Medical Center
Maywood, Illinois 60153
United States
Carle Cancer Center
Urbana, Illinois 61801
United States
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa 50023
United States
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
Clive, Iowa 50325
United States
Iowa Methodist Medical Center
Des Moines, Iowa 50309
United States
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa 50309
United States
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines, Iowa 50314
United States
UI Health Care Mission Cancer and Blood - Waukee Clinic
Waukee, Iowa 50263
United States
University of Kansas Cancer Center
Kansas City, Kansas 66160
United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas 66205
United States
Walter Reed National Military Medical Center
Bethesda, Maryland 20889-5600
United States
Boston Medical Center
Boston, Massachusetts 02118
United States
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan 48109
United States
Henry Ford Cancer Institute-Downriver
Brownstown, Michigan 48183
United States
Henry Ford Macomb Hospital-Clinton Township
Clinton Township, Michigan 48038
United States
Henry Ford Medical Center-Fairlane
Dearborn, Michigan 48126
United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan 48201
United States
Henry Ford Hospital
Detroit, Michigan 48202
United States
Weisberg Cancer Treatment Center
Farmington Hills, Michigan 48334
United States
Allegiance Health
Jackson, Michigan 49201
United States
Karmanos Cancer Institute at McLaren Greater Lansing
Lansing, Michigan 48910
United States
Henry Ford Medical Center-Columbus
Novi, Michigan 48377
United States
Henry Ford West Bloomfield Hospital
West Bloomfield, Michigan 48322
United States
Henry Ford Wyandotte Hospital
Wyandotte, Michigan 48192
United States
Mercy Hospital
Coon Rapids, Minnesota 55433
United States
Fairview Southdale Hospital
Edina, Minnesota 55435
United States
Abbott-Northwestern Hospital
Minneapolis, Minnesota 55407
United States
Mayo Clinic in Rochester
Rochester, Minnesota 55905
United States
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota 55416
United States
Regions Hospital
Saint Paul, Minnesota 55101
United States
United Hospital
Saint Paul, Minnesota 55102
United States
Baptist Memorial Hospital and Cancer Center-Oxford
Oxford, Mississippi 38655
United States
Baptist Memorial Hospital and Cancer Center-Desoto
Southhaven, Mississippi 38671
United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri 63376
United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri 63141
United States
Washington University School of Medicine
St Louis, Missouri 63110
United States
Siteman Cancer Center-South County
St Louis, Missouri 63129
United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri 63136
United States
Nebraska Medicine-Bellevue
Bellevue, Nebraska 68123
United States
Nebraska Medicine-Village Pointe
Omaha, Nebraska 68118
United States
University of Nebraska Medical Center
Omaha, Nebraska 68198
United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey 07748
United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey 07645
United States
Memorial Sloan Kettering Commack
Commack, New York 11725
United States
Memorial Sloan Kettering Westchester
Harrison, New York 10604
United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York 10032
United States
Memorial Sloan Kettering Cancer Center
New York, New York 10065
United States
University of Rochester
Rochester, New York 14642
United States
Novant Health Presbyterian Medical Center
Charlotte, North Carolina 28204
United States
Duke University Medical Center
Durham, North Carolina 27710
United States
Novant Health Cancer Institute - Huntersville
Huntersville, North Carolina 28078
United States
Novant Health Cancer Institute - Mooresville
Mooresville, North Carolina 28117
United States
Novant Health Forsyth Medical Center
Winston-Salem, North Carolina 27103
United States
Case Western Reserve University
Cleveland, Ohio 44106
United States
Riverside Methodist Hospital
Columbus, Ohio 43214
United States
Providence Newberg Medical Center
Newberg, Oregon 97132
United States
Providence Willamette Falls Medical Center
Oregon City, Oregon 97045
United States
Providence Portland Medical Center
Portland, Oregon 97213
United States
Providence Saint Vincent Medical Center
Portland, Oregon 97225
United States
Oregon Health and Science University
Portland, Oregon 97239
United States
Geisinger Medical Center
Danville, Pennsylvania 17822
United States
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania 19104
United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania 19107
United States
Geisinger Wyoming Valley/Henry Cancer Center
Wilkes-Barre, Pennsylvania 18711
United States
Baptist Memorial Hospital and Cancer Center-Collierville
Collierville, Tennessee 38017
United States
Baptist Memorial Hospital and Cancer Center-Memphis
Memphis, Tennessee 38120
United States
Houston Methodist San Jacinto Hospital
Baytown, Texas 77521
United States
Houston Methodist Cypress Hospital
Cypress, Texas 77429
United States
Houston Methodist Hospital
Houston, Texas 77030
United States
M D Anderson Cancer Center
Houston, Texas 77030
United States
Methodist Willowbrook Hospital
Houston, Texas 77070
United States
Houston Methodist West Hospital
Houston, Texas 77094
United States
Houston Methodist Saint John Hospital
Nassau Bay, Texas 77058
United States
Houston Methodist Sugar Land Hospital
Sugar Land, Texas 77479
United States
Houston Methodist The Woodlands Hospital
The Woodlands, Texas 77385
United States
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin 54301
United States
Saint Vincent Hospital Cancer Center at Saint Mary's
Green Bay, Wisconsin 54303
United States
Gundersen Lutheran Medical Center
La Crosse, Wisconsin 54601
United States
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin 53718
United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin 53792
United States
Medical College of Wisconsin
Milwaukee, Wisconsin 53226
United States
Saint Vincent Hospital Cancer Center at Oconto Falls
Oconto Falls, Wisconsin 54154
United States
Saint Vincent Hospital Cancer Center at Sheboygan
Sheboygan, Wisconsin 53081
United States
Sheboygan Physicians Group
Sheboygan, Wisconsin 53081
United States
Saint Vincent Hospital Cancer Center at Sturgeon Bay
Sturgeon Bay, Wisconsin 54235-1495
United States