A Study of Daratumumab-Based Therapies in Participants With Amyloid Light Chain (AL) Amyloidosis (AQUARIUS)
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| ClinicalTrials.gov Identifier: NCT05250973 |
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Recruitment Status :
Recruiting
First Posted : February 22, 2022
Last Update Posted : May 3, 2023
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Sponsor:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Janssen Research & Development, LLC
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Brief Summary:
The purpose of this study is to characterize cardiac safety of Daratumumab, Cyclophosphamide, Bortezomib, and Dexamethasone (D-VCd) treatment regimens (Arm A: immediate daratumumab + VCd treatment and Arm B: daratumumab + deferred VCd) in newly diagnosed systemic amyloid light chain (AL) amyloidosis with cardiac involvement and to identify potential mitigation strategies for cardiac toxicity (cohort 1); to characterize the pharmacokinetics of subcutaneous (SC) daratumumab, among racial and ethnic minorities, including Black or African American, with newly diagnosed AL amyloidosis treated with D-VCd (cohort 2).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Amyloidosis | Drug: Daratumumab Drug: Cyclophosphamide Drug: Bortezomib Drug: Dexamethasone | Phase 2 |
Expanded Access : Janssen Research & Development, LLC has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.
AL amyloidosis is a rare disorder caused by clonal plasma cells that secrete immunoglobulin light chains that misfold into insoluble amyloid. The insoluble amyloid gets deposited in vital organs which results in serious and life-threatening organ dysfunction. Daratumumab is a human immunoglobulin (IgG1K) monoclonal antibody (mAb) that binds with high affinity to a unique epitope on cluster of differentiation 38 (CD38), a transmembrane glycoprotein. It is a targeted immunotherapy directed towards tumor cells that overexpress CD38. Participants will be enrolled into 2 cohorts based on cardiac involvement at baseline for cohort 1 and racial or ethnic minority with at least one organ involved for cohort 2. This study aims to generate data on risk factors for cardiac toxicity and to evaluate the cardiac safety of the proposed treatment regimens and identify potential mitigation strategies for cardiac toxicity such as deferred VCd treatment, The study will consist of screening phase (up to 28 days) and treatment phase with up to 24 treatment cycles (each cycle is 28 days). Safety assessment will include adverse events (AEs), serious adverse events (SAEs), physical examinations, Eastern Cooperative Oncology Group (ECOG) criteria for performance status, laboratory tests and vital signs. The overall duration of the study will be up to 3 years and 8 months.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 150 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 2, Multicohort Study of Daratumumab-Based Therapies in Participants With Amyloid Light Chain (AL) Amyloidosis |
| Actual Study Start Date : | March 1, 2022 |
| Estimated Primary Completion Date : | November 29, 2024 |
| Estimated Study Completion Date : | November 18, 2025 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Amyloidosis
Drug Information available for:
Daratumumab
| Arm | Intervention/treatment |
|---|---|
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Experimental: Cohort1 (Arm A): Immediate Daratumumab + Cyclophosphamide, Bortezomib and Dexamethasone (VCd)
Participants with newly diagnosed systemic amyloid light chain (AL) amyloidosis with Mayo Cardiac Stage II and IIIa cardiac involvement will receive daratumumab 1800 milligrams (mg) subcutaneously (SC) starting on Day 1 once weekly (q1w) up to Day 22 for cycles 1-2, on Days 1 and 15 for cycles 3-6, and on Day 1 for cycles 7-24 of a 28-day cycle. Participants will also receive VCd (cyclophosphamide 300 milligrams per meter square [mg/m^2] either orally or intravenously [IV], bortezomib 1.3 mg/m^2 SC, dexamethasone 40 mg weekly either orally or IV) weekly starting at Cycle 1 Day 1 up to Day 22 in every 28-day cycle for a maximum of 6 cycles (Cycle 6 Day 22).
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Drug: Daratumumab
Daratumumab will be administered subcutaneously.
Other Name: JNJ-54767414 Drug: Cyclophosphamide Cyclophosphamide will be administered either orally or IV. Drug: Bortezomib Bortezomib will be administered by SC injection. Drug: Dexamethasone Dexamethasone will be administered orally or IV. |
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Experimental: Cohort1 (Arm B): Daratumumab + Deferred VCd
Participants with newly diagnosed systemic AL amyloidosis with Mayo Cardiac Stage II and IIIa cardiac involvement will receive SC daratumumab 1800mg on Day 1 once weekly (q1w) up to Day 22 for cycles 1-2, on Days 1 and 15 for cycles 3-6, and on Day 1 for cycles 7-24 of a 28-day cycle. Participants will also receive VCd (Cyclophosphamide 300 mg/m^2 either orally or IV, Bortezomib 1.3 mg/m^2 SC, Dexamethasone 40 mg weekly either orally or IV) starting at Cycle 4 Day 1, weekly (Days 1, 8, 15, 22) in every 28-day cycle for a maximum of 6 cycles (Cycle 9 Day 22).
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Drug: Daratumumab
Daratumumab will be administered subcutaneously.
Other Name: JNJ-54767414 Drug: Cyclophosphamide Cyclophosphamide will be administered either orally or IV. Drug: Bortezomib Bortezomib will be administered by SC injection. Drug: Dexamethasone Dexamethasone will be administered orally or IV. |
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Experimental: Cohort 2: Daratumumab + VCd
Participants with racial and ethnic minorities, including Black or African American participants, with newly diagnosed AL amyloidosis will receive SC injection of daratumumab 1800 mg SC on Day 1 once weekly (q1w) up to Day 22 for cycles 1-2, on Days 1 and 15 for cycles 3-6, and on Day 1 for cycles 7-24 of a 28-day cycle. Participants will also receive VCd (cyclophosphamide 300 milligrams per meter square [mg/m^2] either orally or intravenously [IV], bortezomib 1.3 mg/m^2 SC, dexamethasone 40 mg weekly either orally or IV) weekly starting at Cycle 1 Day 1 up to Day 22 in every 28-day cycle for a maximum of 6 cycles (Cycle 6 Day 22).
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Drug: Daratumumab
Daratumumab will be administered subcutaneously.
Other Name: JNJ-54767414 Drug: Cyclophosphamide Cyclophosphamide will be administered either orally or IV. Drug: Bortezomib Bortezomib will be administered by SC injection. Drug: Dexamethasone Dexamethasone will be administered orally or IV. |
Primary Outcome Measures :
- Number of Participants with Cardiac Events of Any Toxicity Grade [ Time Frame: Up to 12 months ]Number of participants with cardiac events of any toxicity grade will be reported.
- Observed Concentration Immediately Prior to the Next Study Treatment Administration (Ctrough) [ Time Frame: Cycle 3 Day 1 predose (each cycle is of 28 days) ]Ctrough is defined as the observed concentration immediately prior to the next study treatment administration.
Secondary Outcome Measures :
- Overall Complete Hematologic Response (HemCR) Rate [ Time Frame: Up to 3 years ]Overall HemCR rate is defined as percentage of participants who achieve HemCR during or after the study treatment.
- HemCR Rate [ Time Frame: At 6 months ]HemCR rate at 6 month is defined as percentage of participants who achieve HemCR at 6 month during or after the study treatment.
- Very Good Partial Response (VGPR) or Better Rate [ Time Frame: Up to 3 Years ]Hematologic greater than or equal to (>=) VGPR rate is defined as percentage of participants who achieve hematologic response of VGPR or better.
- Time to HemCR or (VGPR or Better) [ Time Frame: Up to 3 years ]For participants who achieve HemCR (or >=VGPR), time to HemCR (or >=VGPR) is defined as the time between the date of randomization (Cohort1)/first treatment (Cohort 2) and the first efficacy evaluation at which the participant has met all criteria for hematologic complete response (CR) (or >=VGPR).
- Duration of Response (HemCR and VGPR or Better) [ Time Frame: Up to 3 years ]For participants who achieve HemCR (or >=VGPR), duration of HemCR (or >=VGPR) is defined as the time between the date of initial documentation of HemCR (or >=VGPR) to the date of first documented evidence of hematologic progressive disease or death, whichever comes first.
- Organ Response Rate (OrRR) [ Time Frame: Up to 3 years ]Organ response rate is defined as the percentage of participants who achieve organ response in each corresponding organ (kidney, heart, liver).
- Overall Survival (OS) [ Time Frame: Up to 3 years ]OS is measured from the date of randomization (Cohort 1)/first treatment (Cohort 2) to the date of the participant's death.
- Time to Next Treatment (TNT) [ Time Frame: Up to 3 Years ]TNT for amyloid light chain (AL) amyloidosis is defined as the time from the date of randomization (Cohort1)/first treatment (Cohort 2) to the start date of subsequent AL amyloidosis (non-protocol) treatment.
- Number of Participants with Adverse Events (AEs) by Severity [ Time Frame: Up to 3 Years ]Number of participants with AEs by severity will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study.
- Serum Concentration of Daratumumab [ Time Frame: Up to 3 Years ]Serum samples will be analyzed to determine concentrations of daratumumab.
- Number of Participants with Antibodies to Daratumumab [ Time Frame: Up to 3 years ]Number of participants with antibodies to daratumumab will be reported.
- Number of Participants with Antibodies to Recombinant Human Hyaluronidase PH20 Enzyme (rHuPH20) [ Time Frame: Up to 3 years ]Number of participants with antibodies to rHuPH20 will be reported.
- Change from Baseline in Clinical Signs and Symptoms Score of Cardiac AL Amyloidosis [ Time Frame: Baseline up to 3 Years ]Change from baseline in clinical signs and symptoms score of cardiac AL amyloidosis will be reported.
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Cohort 1: Cardiac involvement (amyloid light chain [AL] amyloidosis Mayo Cardiac Stage II and Stage IIIa) with or without other organ(s) involved; Cohort 2: One or more organs impacted by systemic AL amyloidosis according to consensus guidelines
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1 or 2
- A female participant of childbearing potential must have a negative serum or urine test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study
- A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 6 months after receiving the last dose of cyclophosphamide or 100 days after discontinuation of daratumumab, whichever is longer
- Cohort 2 only: self-identified racial and ethnic minorities, including Black or African American
Exclusion Criteria:
- Prior therapy for systemic AL amyloidosis or multiple myeloma including medications that target cluster of differentiation 38 (CD38), with the exception of 160 milligrams(mg) dexamethasone or equivalent corticosteroid maximum exposure prior to randomization/enrollment
- Previous or current diagnosis of symptomatic multiple myeloma per International Myeloma Working Group (IMWG) Criteria
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Participant received any of the following therapies:
- treatment with an investigational drug or used an invasive investigational medical device within 14 days or at least 5 half-lives, whichever is less;
- vaccinated with an investigational vaccine (except for COVID-19) live, attenuated or replicating viral vector vaccines less than (<) 4 weeks prior to randomization/enrollment. Participants who are taking strong Cytochrome P450 3A4(CYP3A4) inducers must discontinue their use at least 5 half-lives prior to the first dose of bortezomib
- Stem cell transplantation -Planned stem cell transplant during the first 9 cycles of protocol therapy are excluded. Stem cell collection during the first 9 cycles of protocol therapy is permitted
- Grade 2 sensory or Grade 1 painful peripheral neuropathy
Information from the National Library of Medicine
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): NCT05250973
Contacts
| Contact: Study Contact | 844-434-4210 | Participate-In-This-Study@its.jnj.com |
Locations
Show 37 study locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
| Study Director: | Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC |
| Responsible Party: | Janssen Research & Development, LLC |
| ClinicalTrials.gov Identifier: | NCT05250973 |
| Other Study ID Numbers: |
CR109160 2021-002639-48 ( EudraCT Number ) 54767414AMY2009 ( Other Identifier: Janssen Research & Development, LLC ) |
| First Posted: | February 22, 2022 Key Record Dates |
| Last Update Posted: | May 3, 2023 |
| Last Verified: | May 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu |
| URL: | https://www.janssen.com/clinical-trials/transparency |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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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 |