- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03283917
Daratumumab, Ixazomib, and Dexamethasone in AL Amyloidosis
A Safety Study of Daratumumab, Ixazomib, and Dexamethasone in AL Amyloidosis
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. To confirm the safety and tolerability of daratumumab, ixazomib, and dexamethasone (DId) in patients with amyloid light chain (AL) amyloidosis.
II. To determine the recommended phase 2 dose (RP2D) of daratumumab, ixazomib, and dexamethasone in subjects with AL amyloidosis.
SECONDARY OBJECTIVES:
I. To determine the hematologic response rate of daratumumab, ixazomib, and dexamethasone in patients with AL amyloidosis.
II. To determine cardiac and renal organ response rate of daratumumab, ixazomib, and dexamethasone in patients with AL amyloidosis.
III. To determine time to next therapy. IV. To determine the time to response. V. To determine the duration of response. VI. To determine progression free survival (PFS). VII. To determine overall survival (OS).
OUTLINE: This is a dose-escalation study of dexamethasone.
Participants receive daratumumab intravenously (IV) over 3.5-6.5 hours on days 1, 8, 15, and 22 of courses 1-2, on days 1 and 15 of courses 3-6, and on day 1 of courses 7-12. Participants also receive ixazomib orally (PO) on days 1, 8, and 15, and dexamethasone IV over 15 minutes or PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unaccepted toxicity.
After completion of study treatment, participants are followed up at 30 days and then every 90 days for 24 months.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Hans C. Lee, MD
- Phone Number: 713-792-2860
- Email: hclee@mdanderson.org
Study Locations
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Texas
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Houston, Texas, United States, 77030
- M D Anderson Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Diagnosis of primary systemic AL amyloidosis of tissue as determined by: a. Congo red staining of tissue showing apple green birefringence AND b. Clonal plasma cell disorder as determined by: i. Immunohistochemistry, in situ hybridization (ISH) or flow cytometry demonstrating kappa or lambda light chain restriction on bone marrow biopsy AND/OR ii. Monoclonal protein on serum or urine electrophoresis/immunofixation OR abnormal free light chain ratio
- Newly diagnosed OR relapsed and/or refractory AL amyloidosis. Newly diagnosed patients must be treatment naive without previous plasma cell-directed therapy with the exception of a maximum of 160 mg dexamethasone or equivalent prior to dosing on protocol. Relapsed and/or refractory is defined as follows: a. Clonal relapse after at least one previous line of therapy or high-dose chemotherapy and autologous stem cell transplantation OR b. Refractory disease to prior therapy defined as less than a hematologic very good partial response (VGPR). If previous therapy was autologous stem cell transplant (SCT), must be >= 3 months after SCT
- Measurable disease defined by: a. Monoclonal protein in the serum or urine by immunofixation OR plasmacytosis of bone marrow with monoclonal staining for kappa or lambda light-chain isotype b. dFLC >= 50 mg/L (dFLC=difference in involved and uninvolved serum free light-chain levels)
- Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care
Female patients who:
- Are postmenopausal for at least 1 year before the screening visit, OR
- Are surgically sterile, OR
- If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, OR
- Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)
Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following:
- Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR
- Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)
- Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2
- Absolute neutrophil count (ANC) >= 1,000/mm^3
- Platelet count >= 75,000/mm^3. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment
- Total bilirubin =< 1.5 x the upper limit of the normal range (ULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN
- Calculated creatinine clearance >= 10 mL/min
Exclusion Criteria:
- Non-AL amyloidosis
- Clinically overt myeloma a.) Lytic bone lesions or biopsy proven plasmacytoma b.) Hypercalcemia (corrected for albumin) > 11 mg/dL unexplained by other causes
- Clinically significant cardiac disease defined by any of the following criteria: a.) New York Heart Association (NYHA) class IV heart failure b.) N-terminal prohormone of brain natriuretic peptide (NT-ProBNP) > 8500 ng/L c.) Symptomatic orthostatic hypotension with supine systolic blood pressure < 90 mm Hg d.) Unstable cardiac arrhythmia e.) Unstable angina f.) Myocardial infarction within the past 6 months
- Severe obstructive airway disease defined by forced expiratory volume at one second (FEV1) < 50%
- Female patients who are lactating or have a positive serum pregnancy test during the screening period
- Failure to have fully recovered (ie, =< grade 1 toxicity) from the reversible effects of prior chemotherapy
- Major surgery within 14 days before enrollment
- Radiotherapy within 14 days before enrollment. If the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the ixazomib
- Infection requiring systemic intravenous antibiotic therapy or other serious infection within 14 days before study enrollment
- Systemic treatment, within 14 days before the first dose of and dexamethasone (DId), with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort
- Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive
- Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
- Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
- Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing
- Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
- Patient has >= grade 3 peripheral neuropathy, or grade 2 with pain on clinical examination during the screening period
- Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial
- Patients that have previously been treated with daratumumab or ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (daratumumab, ixazomib, dexamethasone)
Participants receive daratumumab IV over 3.5-6.5 hours on days 1, 8, 15, and 22 of courses 1-2, on days 1 and 15 of courses 3-6, and on day 1 of courses 7-12.
Participants also receive ixazomib PO on days 1, 8, and 15, and dexamethasone IV over 15 minutes or PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unaccepted toxicity.
|
Given IV
Other Names:
Given IV or PO
Other Names:
Given PO
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Dose limiting toxicity rate
Time Frame: Up to 28 days
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Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.
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Up to 28 days
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Recommended phase 2 dose of daratumumab, ixazomib, and dexamethasone
Time Frame: Up to 24 months
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Up to 24 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Overall hematologic response rate
Time Frame: Up to 24 months
|
Up to 24 months
|
Time to response
Time Frame: Up to 24 months
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Up to 24 months
|
Duration of response
Time Frame: Up to 24 months
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Up to 24 months
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Time to next therapy
Time Frame: Up to 24 months
|
Up to 24 months
|
Progression free survival
Time Frame: Up to 24 months
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Up to 24 months
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Overall survival
Time Frame: Up to 24 months
|
Up to 24 months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Hans C Lee, M.D. Anderson Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Paraproteinemias
- Proteostasis Deficiencies
- Neoplasms, Plasma Cell
- Immunoglobulin Light-chain Amyloidosis
- Amyloidosis
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Protease Inhibitors
- Dermatologic Agents
- Glycine Agents
- Dexamethasone
- Dexamethasone acetate
- BB 1101
- Daratumumab
- Ixazomib
- Glycine
- Ichthammol
Other Study ID Numbers
- 2017-0243 (Other Identifier: M D Anderson Cancer Center)
- NCI-2018-01044 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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