Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Dermatologic Agents

Anti-Infective Agents

Dexamethasone

Lenalidomide

Bortezomib

Daratumumab

Dexamethasone acetate

BB 1101

Ichthammol

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

HIV Protease Inhibitors

Protease Inhibitors

Enzyme Inhibitors

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

INDUCTION: All patients receive standard induction therapy comprising the following: daratumumab subcutaneously (SC) on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7-9, lenalidomide orally (PO) daily on days 1-21, and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 9 cycles in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: Patients receive bortezomib SC on days 1, 8, and 15, daratumumab SC on day 1, lenalidomide PO daily on days 1-21, and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 9 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive lenalidomide PO daily on days 1-21 and daratumumab SC on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: Patients receive daratumumab SC on day 1, lenalidomide PO daily on days 1-21, and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 9 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive lenalidomide PO daily on days 1-21, and daratumumab SC on day 1. Cycles repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Daratumumab and Hyaluronidase-fihj

Quality-of-Life Assessment

Site Public Contact

Alison K. Conlin

Richard L. Deming

Muhammad Husnain

Jay W. Carlson

Sabrina Browning

Gregory A. Masters

Elie G. Dib

Alexander W. Brown

John M. Schallenkamp

Priyank P. Patel

Bryan A. Faller

Patrick A. Hagen

Pritesh Patel

Robert M. Eisner

Shaji K Kumar

This phase III trial compares the combination of four drugs (daratumumab, bortezomib, lenalidomide and dexamethasone) to the use of a three drug combination (daratumumab, lenalidomide and dexamethasone). Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as lenalidomide, 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. Daratumumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Anti-inflammatory drugs, such as dexamethasone lower the body's immune response and are used with other drugs in the treatment of some types of cancer. Adding bortezomib to daratumumab, lenalidomide, and dexamethasone may be more effective in shrinking the cancer or preventing it from returning, compared to continuing on daratumumab, lenalidomide, and dexamethasone.

PRIMARY OBJECTIVE:

I. To determine if bortezomib, daratumumab and hyaluronidase-fihj (daratumumab), lenalidomide and dexamethasone (Btz-DRd) consolidation followed by daratumumab and lenalidomide (DR) maintenance after standard induction therapy with daratumumab, lenalidomide and dexamethasone (DRd) results in superior overall survival compared to DRd consolidation followed by DR maintenance, in minimal residual disease (MRD) positive patients.

SECONDARY OBJECTIVES:

I. To determine if Btz-DRd consolidation followed by DR maintenance after standard induction therapy with DRd results in superior overall survival compared to DRd consolidation followed by DR maintenance in MRD negative patients.

II. To determine if Btz-DRd consolidation followed by DR maintenance after standard induction therapy with DRd results in superior progression-free survival compared to DRd consolidation followed by DR maintenance in both MRD positive and MRD negative patients.

III. To describe and compare the incidence of toxicities during consolidation between Btz-DRd and DRd arms.

IV. To assess the improvement in MRD negative rate with consolidation among patients who are MRD positive after induction.

V. To assess the sustained MRD negative rate among patients who are MRD negative after induction.

PATIENT REPORTED OUTCOMES (PRO) OBJECTIVES:

I. To quantify the extent to which the addition of bortezomib to DRd over consolidation treatment contributes to neuropathy and associated physical and functional impairments. (Primary PRO Objective) II. To evaluate the rate of resolution of neurotoxicity and associated physical and functional impairments following completion of consolidation therapy. (Secondary PRO Objective) III. To investigate the relationship between MRD status and patient reported health-related quality of life outcomes. (Exploratory PRO Objective) IV. To evaluate attributes of select patient reported treatment-emergent symptomatic adverse events (PRO- Common Terminology Criteria for Adverse Events \[CTCAE\]) longitudinally and compare responses with provider-reported adverse events. (Exploratory PRO Objective) V. To tabulate PRO compliance and completion rates. (Exploratory PRO Objective)

IMAGING OBJECTIVES:

I. To evaluate the association between post-induction fludeoxyglucose F-18 (18F-FDG) positron emission tomography (PET)/computed tomography (CT) and patient outcomes (overall survival \[OS\] and progression-free survival \[PFS\]). (Primary Imaging Objective) II. To evaluate the association between baseline 18F-FDG PET/CT and patient outcomes (PFS and OS). (Secondary Imaging Objective) III. To compare overall survival with the addition of Bortezomib to consolidation DRd therapy among 18F-FDG PET/CT-positive and 18F-FDG PET/CT-negative subgroups. (Secondary Imaging Objective) IV. To evaluate the ability of baseline 18F-FDG PET/CT to predict post-induction depth of response as measured by MRD assessment. (Secondary Imaging Objective) V. To evaluate the ability of post-induction 18F-FDG PET/CT to predict MRD conversion post-consolidation. (Secondary Imaging Objective) VI. To utilize 18F-FDG PET/CT, standard risk factors and clinical data to identify distinct subgroups with differing patient outcomes (PFS and OS). (Exploratory Imaging Objective) VII. To compare the various qualitative 18F-FDG PET/CT criteria to determine which criteria yields superior risk stratification. (Exploratory Imaging Objective)

OUTLINE:

ARM A (INDUCTION): All patients receive standard induction therapy comprising the following: daratumumab subcutaneously (SC) on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7-9, lenalidomide orally (PO) daily on days 1-21, and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 9 cycles in the absence of disease progression or unacceptable toxicity.

After completion of standard induction therapy, patients are randomized to 1 of 2 arms.

ARM B:

CONSOLIDATION: Patients receive bortezomib SC on days 1, 8, and 15, daratumumab SC on day 1, lenalidomide PO daily on days 1-21, and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 9 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive lenalidomide PO daily on days 1-21 and daratumumab SC on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM C:

CONSOLIDATION: Patients receive daratumumab SC on day 1, lenalidomide PO daily on days 1-21, and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 9 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive lenalidomide PO daily on days 1-21, and daratumumab SC on day 1. Cycles repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months if less than 2 years from study entry, every 6 months if 2-5 years from study entry, then annually for up to 15 years from study entry.

Testing the Use of Combination Therapy in Adult Patients With Newly Diagnosed Multiple Myeloma, the EQUATE Trial

Effective Quadruplet Utilization After Treatment Evaluation (EQUATE): A Randomized Phase 3 Trial for Newly Diagnosed Multiple Myeloma Not Intended for Early Autologous Transplantation

Calculated as the difference after completion of 9 cycles of consolidation therapy from end of induction. Scores can range from a minimum of 0 and a maximum of 44. A higher score on this assessment means a worse outcome.

The FACT-G is a single outcome measure made up of the PWB and FWB components. Scores range from a minimum of 0 and a maximum of 56. For this assessment, a higher score means a better outcome.

Presence, frequency, interference, amount and/or severity of select PRO-CTCAEs tabulated at each measurement.

Defined as the proportion of patients who submit the given PRO instrument among those eligible at each time point which excludes those missing by design (due to death or disease progression, early treatment discontinuation).

Defined as the proportion of patients who complete given PRO instrument based on the instrument's scoring system among those eligible at each time point.

Will be estimated using the Kaplan-Meier (KM) method and compared using a stratified log-rank test. Stratified cox proportional hazards regression will produce treatment hazard ratio (bortezomib, daratumumab and hyaluronidase-fihj (daratumumab), lenalidomide and dexamethasone \[Btz-DRd\] then daratumumab, lenalidomide and dexamethasone \[DRd\] then daratumumab and lenalidomide \[DR\]).

Patients alive without disease progression will be censored at date of last disease evaluation. Only deaths that occur within 3 months of the last disease evaluation are considered events.

Defined as the proportion of patients with the FACT-Ntx TOI score returning to baseline level reached at consolidation randomization after experiencing a MID decrease while on up to 1 year of maintenance.

National Cancer Institute (NCI)

ECOG-ACRIN Cancer Research Group

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Digestive System Diseases

Skin and Connective Tissue Diseases

Gland and Hormone Related Diseases

Symptoms and General Pathology

Lung Neoplasms

Carcinoma

Prostatic Neoplasms

Adenocarcinoma

Stomach Neoplasms

Breast Neoplasms

Esophageal Neoplasms

Pancreatic Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Lymphoma

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Urinary Bladder Neoplasms

Melanoma

Thyroid Neoplasms

Thyroid Diseases

Carcinoma, Renal Cell

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Sarcoma

Kidney Neoplasms

Colorectal Neoplasms

Lymphatic Diseases

Neoplasms, Glandular and Epithelial

Breast Diseases

Skin Diseases

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Gonadal Disorders

Stomach Diseases

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Urologic Neoplasms

Urinary Bladder Diseases

Urologic Diseases

Head and Neck Neoplasms

Esophageal Diseases

Myeloproliferative Disorders

Bone Marrow Diseases

Kidney Diseases

Stomach Cancer

Esophageal Cancer

Pancreatic Cancer

Myeloid Leukemia

Acute Myeloid Leukemia

Ovarian Cancer

Ovarian Epithelial Cancer

Lymphosarcoma

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Renal Cell Carcinoma

Acute Non Lymphoblastic Leukemia

Chronic Lymphocytic Leukemia

Participants complete a questionnaire at baseline. Participants undergo collection of blood samples at registration and at 12 months after registration. Patients with a cancer diagnosis may undergo collection of tissue samples at registration and 12 months after registration.

Questionnaire Administration

Undergo collection of tissue and blood samples

Biospecimen Collection

Marie Wood, MD

Nicholas DiBella

John A. Ellerton

Shahzad Siddique

Luis Mariscal

Lisa Bailey

Mark E. Reeves

Pankaj Gupta

Constantin A. Dasanu

Tyler Y. Kang

Gigi Q. Chen

Jessica D. McDermott

Marie E. Wood

Talib Dosani

Lucile L. Adams-Campbell

Vijaya K. Gadiyaram

Alan Bruce Grosset

Christopher M. Reynolds

Wayne B. Harris

William E. Burak

This study collects blood and tissue samples from patients with cancer and without cancer to evaluate tests for early cancer detection. Collecting and storing samples of blood and tissue from patients with and without cancer to study in the laboratory may help researchers develop tests for the early detection of cancers.

PRIMARY OBJECTIVE:

I. To provide a blinded reference set of cancer versus (vs.) non-cancer blood samples that will be used to validate assays for inclusion in a prospective clinical trial focused on utility of blood-based multi-cancer early detection.

SECONDARY OBJECTIVES:

I. Evaluate test performance at the time of initial cancer diagnosis by tumor type.

II. Evaluate test performance at the time of initial cancer diagnosis by clinical stage.

OUTLINE:

Participants complete a questionnaire at baseline. Participants undergo collection of blood samples at registration and at 12 months after registration. Patients with a cancer diagnosis may undergo collection of tissue samples at registration and 12 months after registration.

After completion of study, participants are followed up at 1 year.

Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection

Blinded Reference Set for Multicancer Early Detection Blood Tests

Diagnostic ability will be assessed across the entire cohort of 2000 subjects by estimating the sensitivity and specificity with 95% confidence intervals.

Diagnostic ability is assessed within each cancer type and within each cancer type and stage combination by estimating the sensitivity and specificity with 95% confidence intervals. The width of these confidence intervals will vary by sample size and the sensitivity and specificity rates.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Testing the Use of Combination Therapy in Adult Patients With Newly Diagnosed Multiple Myeloma, the EQUATE Trial	NCT04566328	Plasma Cell Mye... RISS Stage I Pl... RISS Stage II P...	Bortezomib Daratumumab and... Dexamethasone Lenalidomide Quality-of-Life...	18 Years -	Eastern Cooperative Oncology Group
Testing the Use of Combination Therapy in Adult Patients With Newly Diagnosed Multiple Myeloma, the EQUATE Trial	NCT04566328	Plasma Cell Mye... RISS Stage I Pl... RISS Stage II P...	Bortezomib Daratumumab and... Dexamethasone Lenalidomide Quality-of-Life...	18 Years -	Eastern Cooperative Oncology Group
Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection	NCT05334069	Acute Lymphobla... Acute Myeloid L... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Chronic Lymphoc... Chronic Myeloid... Gastroesophagea... Head and Neck C... Hematopoietic a... Invasive Breast... Kidney Carcinom... Malignant Hepat... Malignant Solid... Melanoma Muscle-Invasive... RISS Stage I Pl... RISS Stage II P... RISS Stage III ... Sarcoma Stage I Bladder... Stage I Breast ... Stage I Colorec... Stage I Esophag... Stage I Gastric... Stage I Lung Ca... Stage I Ovarian... Stage I Pancrea... Stage I Prostat... Stage I Uterine... Stage II Bladde... Stage II Breast... Stage II Colore... Stage II Esopha... Stage II Gastri... Stage II Lung C... Stage II Ovaria... Stage II Pancre... Stage II Prosta... Stage II Uterin... Stage III Bladd... Stage III Breas... Stage III Color... Stage III Esoph... Stage III Gastr... Stage III Lung ... Stage III Ovari... Stage III Pancr... Stage III Prost... Stage III Uteri... Stage IV Bladde... Stage IV Breast... Stage IV Colore... Stage IV Esopha... Stage IV Gastri... Stage IV Lung C... Stage IV Ovaria... Stage IV Pancre... Stage IV Prosta... Stage IV Uterin... Thyroid Gland C...	Questionnaire A... Biospecimen Col...	40 Years - 75 Years	Alliance for Clinical Trials in Oncology

Spots Global Cancer Trial Database for riss stage ii plasma cell myeloma