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AL AmyloidosisPhase 1NCT04754945

Isatuximab as Upfront Therapy for the Treatment of High Risk AL Amyloidosis

A Phase 1 study testing Bortezomib, Cyclophosphamide and Dexamethasone in people with AL Amyloidosis, run by Emory University at 6 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This phase I trial studies the side effects of isatuximab and to see how well it works in treating patients with high risk immunoglobulin light chain amyloidosis (AL amyloidosis). Isatuximab is a monoclonal antibody that 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
Conditions the study is for
AL Amyloidosis
What is being tested?
Bortezomib, Cyclophosphamide and Dexamethasone
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
6 sitesUnited States
Study dates
28 Apr 2021to 24 Jul 2028
Phase
Phase 1
Are there results?
Not yet: the study is under way

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

  • Histopathological diagnosis of amyloidosis based on detection by immunohistochemistry (IHC) and polarizing light microscopy of green birefringent material in Congo red-stained tissue specimens in an organ other than bone marrow, characteristic electron microscopy appearance, or mass spectrometry. Specifically for male subjects 70 years of age or older who have cardiac involvement only and subjects of African descent, mass spectrometry typing of AL amyloid in a tissue biopsy is recommended to rule out other types of amyloidosis such as age-related amyloidosis or hereditary amyloidosis (ATTR mutation)
  • Must have evidence of high risk AL amyloidosis defined as one of the following any time within the 6 months prior to consent:
  • Biomarker-based indicators of severe disease: NT-proBNP > 8500 ng/L OR hs-cTnT >= 50 ng/L
  • BUMC 2019 stage 3b requiring both TnI > 0.1 ng/mL and BNP > 700 pg/mL
  • Mayo 2012 stage 4 that includes each of the following a) cTnT >= 0.025 ng/mL or hs-cTnT >= 40 ng/mL; b) NT-proBNP >= 1800 pg/mL; and c) dFLC >= 180 mg/L
  • Significant AL amyloid related hypotension (systolic blood pressure [SBP] < 100 mm Hg or symptomatic orthostatic hypotension defined as a decrease in systolic blood pressure upon standing of > 20 mm Hg despite medical management [fludrocortisone, midodrine, etc] in the absence of volume depletion)
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  • Absolute neutrophil count (ANC) >= 1000/uL
  • Platelet count >= 50,000 and platelet transfusion independent for 1 week prior to screening
  • Estimated creatinine clearance >= 20 mL/min/1.73 m^2 as defined by Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI)
  • Total bilirubin < 1.5 x institutional upper limit of normal (IULN) except for patients with Gilbert syndrome in which case total bilirubin =< 2 x IULN
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x IULN
  • Left ventricular ejection fraction >= 30%
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting study medication. The effects of protocol therapy on the developing human fetus are unknown. For this reason, FCBP and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 5 months after completion of protocol therapy. Men must refrain from donating sperm during the same period that they must agree to use contraception. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. A female of childbearing potential (FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months
  • Ability to understand and the willingness to sign a written informed consent document
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

Who cannot join

  • > 1 prior line of therapy
  • Refractory to any proteasome inhibitor
  • Prior CD38 antibody exposure
  • Cardiac exclusions:
  • Subjects with a history of sustained ventricular tachycardia EXCEPT in patients with a pacemaker/implantable cardioverter defibrillator (ICD)
  • Baseline QT interval as corrected by institutional rate correction algorithm (e.g. corrected QT interval by Bazett formula [QTc]B or corrected QT interval by Fridericia formula [QTcF]) > 500 msec EXCEPT in patients with a pacemaker
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  • Grade 2 or greater peripheral sensory neuropathy
  • Received any investigational drug within 14 days or 5 half-lives of the investigational drug, whichever is longer
  • Hypersensitivity or history of intolerance to steroids, mannitol, pregelatinized starch, sodium stearyl fumarate, histidine (as base and hydrochloride salt), arginine hydrochloride, poloxamer 188, sucrose or any of the other components of study therapy that are not amenable to premedication with steroids and H2 blockers or would prohibit further treatment with these agents
  • Human immunodeficiency virus (HIV) positive EXCEPT if the patient meets all the following: CD4 > 350 cells/mm3, undetectable viral load, maintained on modern therapeutic regimen utilizing non CYP interacting agents (e.g. excluding ritonavir), and no untreated acquired immune deficiency syndrome defining opportunistic infections
  • Seropositive for hepatitis B surface antigen [HBsAg]) EXCEPT subjects with resolved infection (i.e., subjects who are positive for antibodies to hepatitis B core antigen [antiHBc] and/or antibodies to hepatitis B surface antigen [antiHBs]) 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. Subjects with serologic findings suggestive of HBV vaccination (antiHBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR
  • Seropositive for hepatitis C EXCEPT in the setting of a sustained virologic response [SVR], defined as without viremia for at least 12 weeks after completion of antiviral therapy
  • Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome, wild type or mutated (ATTR) amyloidosis, and Waldenstrom macroglobulinemia
  • Known allergies, hypersensitivity, or intolerance to monoclonal antibodies, hyaluronidase, human proteins, or their excipients (refer to investigational brochure [IB]), or known sensitivity to mammalian-derived products
  • Patients who have had any plasma cell directed treatment, radiotherapy, plasmapheresis, or major surgery (as defined by the investigator) within 1 week prior to cycle 1 day 1 of the study. Patients may be receiving concomitant therapy with low dose corticosteroids (e.g., prednisone up to but no more than 10 mg by mouth daily or its equivalent) for symptom management and comorbid conditions
  • Concurrent medical condition or disease (e.g., active infection requiring treatment with a parenteral antibiotic, active tuberculosis, etc) that would expose excessive risk to the patient or may interfere with compliance or interpretation of the study results
  • Known or suspected of not being able to comply with the study protocol (e.g. alcoholism, drug dependency, or psychological disorder) or the subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (e.g., compromise their well-being) or that could prevent, limit, or confound the protocol-specified assessments
  • Pregnant women are excluded from this study because protocol therapy has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to protocol treatment of the mother, breastfeeding should be discontinued. Women planning to become pregnant 1 year after discontinuation of cyclophosphamide or 3 months following discontinuation of isatuximab

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Emory University Hospital Midtown

    Atlanta, Georgia, 39322

  • UT Southwestern

    Dallas, Texas, 75390

  • Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Columbia University

    New York, New York, 10032

  • University of California

    Orange, California, 92868

Other trials in United States

About this study

Official title: Slow-Go Strategy for High Risk AL Amyloidosis: Isatuximab for Upfront Therapy

This phase I trial studies the side effects of isatuximab and to see how well it works in treating patients with high risk immunoglobulin light chain amyloidosis (AL amyloidosis). Isatuximab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Test the safety and feasibility of isatuximab-based drug treatment.
  2. Evaluate the preliminary efficacy of a slow-go approach in high risk AL amyloid patients.

STUDY TREATMENT

Each patient starts by receiving increasing intensity of treatment for AL Amyloidosis up to maximum tolerance, and then maintenance Isatuximab thereafter for a specified period.

All patients will receive Isatuximab (weekly x 4 then every other week) plus dexamethasone 4 mg PO/IV days weekly. If tolerating Isatuximab/Dex4 (earliest time to escalate C1D15), add Velcade to 1 mg/m2 SQ weekly. If tolerating Isa/Vel1.0/Dex4 (earliest time to escalate C2D1), increase dexamethasone to 12 mg weekly. If tolerating Isa/Velcade1.0/Dex12 (earliest time to escalate C3D1), increase Velcade to 1.3 mg/m2 SQ. If tolerating Isa/Velcade1.3/Dex12 (earliest time to escalate C4D1), add cyclophosphamide 300 mg IV weekly. If tolerating Isa/Velcade1.3/Cy300/Dex12 (earliest time to escalate C5D1), increase cyclophosphamide to 400 mg IV weekly. If tolerating Isa/Velcade1.3/Cy400/Dex12 (earliest time to escalate C6D1), increase cyclophosphamide to 500 mg IV weekly.

Tolerance determined by the patient not reaching an escalation limiting toxicity AND patient approval to dose escalate.

Patients then receive dexamethasone and isatuximab as maintenance treatment twice per month for 12 months in the absence of disease progression or unacceptable toxicity.

Conditions
AL Amyloidosis
Being tested
Bortezomib, Cyclophosphamide, Dexamethasone, Isatuximab
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.

  • BortezomibDrug

    Also called [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341

    Given SC

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV or PO

  • DexamethasoneDrug

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

    Given IV or PO

  • IsatuximabBiological

    Also called Hu 38SB19, Isatuximab-irfc, SAR 650984, SAR650984

    Given IV

Study groups in NCT04754945
Study groupRoleWhat they receive
Treatment (isatuximab, chemotherapy)ExperimentalAll patients will receive Isatuximab plus dexamethasone 4 mg PO/IV days weekly. Based on tolerance, patients will add to their treatment subcutaneous Velcade (earliest time to add Velcade is cycle 1 day 15) and intravenous cyclophosphamide (earliest time to add cyclophosphamide is cycle 4 day 1) Patients then receive dexamethasone and isatuximab as maintenance treatment twice per month for 12 months in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Bortezomib; Drug: Cyclophosphamide; Drug: Dexamethasone; Biological: Isatuximab

What is being measured

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

  1. Event-free proportion

    An event is defined as going off study due to toxicity, death or progression of disease. The events include off-study due to toxicity, death, or progression. The rate will be calculated with an exact 95% confidence interval using the efficacy evaluable population.

    Measured: At 3 months

Secondary outcomes (1)

  1. Complete hematologic response proportion

    Will be calculated with an exact 95% confidence interval.

    Measured: Up to 19 months

Timeline

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

  1. First posted15 Feb 2021
  2. Study start28 Apr 2021
  3. Primary completion6 May 2027 (estimated)
  4. Study completion24 Jul 2028 (estimated)

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
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04754945
Sponsor's protocol ID
STUDY00001440
Other IDs
NCI-2020-06548, Winship5086-20, P30CA138292
Status last verified
Jul 2026
First submitted
9 Feb 2021
Last updated
14 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Bortezomib, Cyclophosphamide and Dexamethasone in people with AL Amyloidosis, run by Emory University at 6 sites 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 15 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: under way, not looking for participants, as of the sponsor's last update on 14 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 6 sites 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?

This study is still under way. Results are not available in the source record yet.

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?

Event-free proportion (time frame: At 3 months). 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 NCT04754945.

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 14 Jul 2026.

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