A Study to Evaluate the Efficacy and Safety of Daratumumab in Combination With Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) Compared to CyBorD Alone in Newly Diagnosed Systemic Amyloid Light-chain (AL) Amyloidosis
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT03201965 |
Recruitment Status :
Active, not recruiting
First Posted : June 28, 2017
Results First Posted : March 4, 2021
Last Update Posted : March 27, 2023
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Amyloidosis | Drug: Cyclophosphamide Drug: Bortezomib Drug: Dexamethasone, 40 mg Drug: Daratumumab | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 416 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Randomized Phase 3 Study to Evaluate the Efficacy and Safety of Daratumumab in Combination With Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) Compared to CyBorD Alone in Newly Diagnosed Systemic AL Amyloidosis |
Actual Study Start Date : | October 5, 2017 |
Actual Primary Completion Date : | February 14, 2020 |
Estimated Study Completion Date : | August 16, 2024 |

Arm | Intervention/treatment |
---|---|
Active Comparator: CyBorD alone (cyclophosphamide/bortezomib/dexamethasone)
Participants will receive dexamethasone (40 milligrams [mg] orally or intravenous [IV] dose), followed by cyclophosphamide (300 milligram per meter square [mg/m^2] orally or IV dose), then bortezomib (1.3 mg/m^2 subcutaneous injection) weekly on Days 1, 8, 15, 22 in every 28-day cycle for a maximum of 6 cycles.
|
Drug: Cyclophosphamide
Participants will receive 300 mg/m^2 of cyclophosphamide as an oral or IV dose. Drug: Bortezomib Participants will receive 1.3 mg/m^2 of bortezomib as an subcutaneous (SC) injection. Drug: Dexamethasone, 40 mg Participants of CyBorD alone arm will receive 40 mg dexamethasone orally or IV dose. Participants of CyBorD plus daratumumab arm will receive dexamethasone 20 mg orally or IV dose as premedication and 20 mg on the day after daratumumab dosing to make a total of 40 mg. |
Experimental: CyBorD plus Daratumumab
Participants will receive dexamethasone (20 mg orally or IV dose as premedication and 20 mg on the day after daratumumab dosing) followed by 1800 mg of daratumumab subcutaneously followed by cyclophosphamide (300 mg/m^2 orally or IV dose weekly) and bortezomib (1.3 mg/m^2 subcutaneous injection weekly) on Days 1, 8, 15, 22 in every 28-day cycle for a maximum of 6 cycles. Daratumumab will be administered weekly for the first 8 weeks (2 cycles), then every 2 weeks for 4 cycles (cycles 3-6), and then every 4 weeks until progression of disease or subsequent therapy for a maximum of 2 years.
|
Drug: Daratumumab
Participants will receive 1800 mg of daratumumab subcutaneously. |
- Percentage of Participants With Overall Complete Hematologic Response (CHR) [ Time Frame: Up to 2.4 years ]Overall CHR rate was defined as percentage of participants who achieved CHR, according to the International Amyloidosis Consensus Criteria. CHR: normalization of free light chain levels and ratio, negative serum, and urine immunofixation. If involved free light chain (iFLC) is less than (<) upper limit of normal (ULN) and serum and urine Immunofixation electrophoresis (IFE) are negative, then neither a normal uninvolved free light chain (uFLC) level nor a normal free light chain (FLC) ratio are required for complete response (CR).

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Histopathological diagnosis of amyloidosis based on detection by immunohistochemistry and polarizing light microscopy of green bi-refringent material in congo red stained tissue specimens (in an organ other than bone marrow) or characteristic electron microscopy appearance
-
Measurable disease of amyloid light-chain (AL) amyloidosis as defined by at least one of the following:
- serum monoclonal (M)-protein greater than or equal (>=) 0.5 grams/deciliter (g/dL) by protein electrophoresis (routine serum protein electrophoresis and immunofixation [IFE] performed at a central laboratory)
- serum free light chain greater than or equal to (>=) 50 milligram/Liter (mg/L) with an abnormal kappa:lambda ratio or the difference between involved and uninvolved free light chains (dFLC) >= 50 mg/L
- One or more organs impacted by AL amyloidosis according to consensus guidelines
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1 or 2
Exclusion Criteria:
- Prior therapy for AL amyloidosis or multiple myeloma including medications that target CD38, with the exception of 160 mg dexamethasone (or equivalent corticosteroid) maximum exposure prior to randomization
- Previous or current diagnosis of symptomatic multiple myeloma, including the presence of lytic bone disease, plasmacytomas, >= 60 percent (%) plasma cells in the bone marrow, or hypercalcemia
-
Evidence of significant cardiovascular conditions as specified below:
- NT-ProBNP > 8500 nanogram per liter (ng/L)
- New York Heart Association (NYHA) classification IIIB or IV heart failure
- Heart failure that in the opinion of the investigator is on the basis of ischemic heart disease (eg, prior myocardial infarction with documented history of cardiac enzyme elevation and electrocardiogram [ECG] changes) or uncorrected valvular disease and not primarily due to AL amyloid cardiomyopathy
- Inpatient admission to a hospital for unstable angina or myocardial infarction within the last 6 months prior to first dose or percutaneous cardiac intervention with recent stent within 6 months or coronary artery bypass grafting within 6 months
- For participants with congestive heart failure, cardiovascular-related hospitalizations within 4 weeks prior to randomization
- Participants with a history of sustained ventricular tachycardia or aborted ventricular fibrillation or with a history of atrioventricular (AV) nodal or sinoatrial (SA) nodal dysfunction for which a pacemaker/implantable cardioverter-defibrillators [ICD] is indicated but not placed (participants who do have a pacemaker/ICD are allowed on study)
- Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) > 500 milliseconds (msec). Participants who have a pacemaker may be included regardless of calculated QTc interval
- Supine systolic blood pressure < 90 millimeter of mercury (mmHg), or symptomatic orthostatic hypotension, defined as a decrease in systolic blood pressure upon standing of > 20 mmHg despite medical management (eg, midodrine, fludrocortisones) in the absence of volume depletion
- Planned stem cell transplant during the first 6 cycles of protocol therapy are excluded. Stem cell collection during the first 6 cycles of protocol therapy is permitted
- Known to be seropositive for human immunodeficiency virus (HIV)
-
Any one of the following:
- Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Participants with resolved infection (ie, participants 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) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded
- Known to be seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy)
- Grade 2 sensory or Grade 1 painful peripheral neuropathy

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03201965

Study Director: | Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC |
Documents provided by Janssen Research & Development, LLC:
Responsible Party: | Janssen Research & Development, LLC |
ClinicalTrials.gov Identifier: | NCT03201965 |
Other Study ID Numbers: |
CR108193 2016-001737-27 ( EudraCT Number ) 54767414AMY3001 ( Other Identifier: Janssen Research & Development, LLC ) |
First Posted: | June 28, 2017 Key Record Dates |
Results First Posted: | March 4, 2021 |
Last Update Posted: | March 27, 2023 |
Last Verified: | March 2023 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Amyloidosis Proteostasis Deficiencies Metabolic Diseases Dexamethasone Cyclophosphamide Bortezomib Daratumumab Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents |
Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal |