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Newly Diagnosed Primary AmyloidosisPhase 1NCT03283917

Daratumumab, Ixazomib, and Dexamethasone in AL Amyloidosis

A Phase 1 study testing Daratumumab, Dexamethasone and Ixazomib in people with Newly Diagnosed Primary Amyloidosis and Recurrent Primary Amyloidosis, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase I trial studies the side effects and best dose of daratumumab, ixazomib, and dexamethasone in treating participants with amyloid light chain amyloidosis. Monoclonal antibodies, such as daratumumab, may interfere with the ability of tumor cells to grow and spread. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Daratumumab, Dexamethasone and Ixazomib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
1 siteUnited States
Study dates
7 Feb 2018to 17 Jun 2026
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Safety Study of Daratumumab, Ixazomib, and Dexamethasone in AL Amyloidosis

This phase I trial studies the side effects and best dose of daratumumab, ixazomib, and dexamethasone in treating participants with amyloid light chain amyloidosis. Monoclonal antibodies, such as daratumumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as ixazomib and dexamethasone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving daratumumab, ixazomib, and dexamethasone may be effective in treating participants with light chain amyloidosis.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
Daratumumab, Dexamethasone, Ixazomib
Medical subject headings
Immunoglobulin Light-chain Amyloidosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DaratumumabBiological

    Also called Anti-CD38 Monoclonal Antibody, Darzalex, HuMax-CD38, JNJ-54767414

    Given IV

  • DexamethasoneDrug

    Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex

    Given IV or PO

  • IxazomibDrug

    Also called MLN-2238, MLN2238

    Given PO

Study groups in NCT03283917
Study groupRoleWhat they receive
Treatment (daratumumab, ixazomib, dexamethasone)ExperimentalParticipants 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.
Receives: Biological: Daratumumab; Drug: Dexamethasone; Drug: Ixazomib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose limiting toxicity rate

    Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.

    Measured: Up to 28 days

  2. Recommended phase 2 dose of daratumumab, ixazomib, and dexamethasone

    Measured: Up to 24 months

Secondary outcomes (6)

  1. Overall hematologic response rate

    Measured: Up to 24 months

  2. Time to response

    Measured: Up to 24 months

  3. Duration of response

    Measured: Up to 24 months

  4. Time to next therapy

    Measured: Up to 24 months

  5. Progression free survival

    Measured: Up to 24 months

  6. Overall survival

    Measured: Up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Sep 2017
  2. Study start7 Feb 2018
  3. Primary completion17 Jun 2026
  4. Study completion17 Jun 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03283917
Sponsor's protocol ID
2017-0243
Other IDs
NCI-2018-01044, 2017-0243
Status last verified
Jul 2026
First submitted
13 Sep 2017
Last updated
9 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Lee HC, Becnel MR, Feng L, Pasvolsky O, Murga A, Johnson RJ, Thomas SK, Bashir Q, Qazilbash MH, Steiner R, Iyer SP, Weber DM, Patel KK, Kaufman GP, Manasanch EE, Orlowski RZ. A Phase 1 Study of Daratumumab, Ixazomib, and Dexamethasone in AL Amyloidosis. Am J Hematol. 2026 Jun;101(6):1187-1191. doi: 10.1002/ajh.70239. Epub 2026 Feb 19. No abstract available.

    PubMed 41714853

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Daratumumab, Dexamethasone and Ixazomib in people with Newly Diagnosed Primary Amyloidosis and Recurrent Primary Amyloidosis, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose limiting toxicity rate (time frame: Up to 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03283917, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2026.

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