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AmyloidosisPhase 2NCT03130348

Ibrutinib With or Without Bortezomib and Dexamethasone in Treating Patients With Relapsed or Refractory Immunoglobulin Light Chain Amyloidosis

A Phase 2 study testing Bortezomib, Dexamethasone and Ibrutinib in people with Amyloidosis and Immunoglobulin Light Chain Deposition, run by Mayo Clinic.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This phase II trial studies how well ibrutinib with or without bortezomib and dexamethasone works in treating patients with immunoglobulin light chain amyloidosis that has come back after a period of improvement or that does not respond to treatment. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Bortezomib, Dexamethasone and Ibrutinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
15 Mar 2018to Apr 2022
Phase
Phase 2
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

  • Histological diagnosis of AL amyloidosis as based on detection by polarizing microscopy of green birefringent material in Congo red-stained tissue specimens; the type must have been confirmed unequivocally
  • Must have had one prior line of systemic therapy for AL; Note: patients who do not achieve at least a PR to frontline therapy in 3 months may be eligible after discussion with study chair
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
  • Absolute neutrophil count (ANC) >= 1000/mm^3
  • Platelet count >= 100,000/mm^3 or >= 50,000/mm^3 if bone marrow involvement independent of transfusion support in either situation
  • Hemoglobin >= 8.0 g/dL
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  • Total bilirubin =< 1.5 x upper limit of normal (ULN) unless due to Gilbert's syndrome or of non-hepatic origin
  • Aspartate transaminase (AST) =< 3 x upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) =< 3 x ULN
  • Creatinine =< 3 mg/dL and creatinine clearance (CrCL) >= 25 ml/min
  • Negative serum pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only
  • Ability to complete questionnaire(s) by themselves or with assistance
  • Ability to provide written informed consent
  • Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
  • Willing to provide bone marrow and blood samples for correlative research purposes

Who cannot join

  • Any of the following:
  • Pregnant persons
  • Nursing persons
  • Persons of childbearing potential who are unwilling to employ adequate contraception; Note: persons of childbearing potential and persons able to father a child who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials; subjects must agree to not donate sperm during and after the study; for persons of childbearing potential, these restrictions apply for 1 month after the last dose of study drug; for persons able to father a child, these restrictions apply for 3 months after the last dose of study drug
  • Concomitant high dose corticosteroids (concurrent use of corticosteroids) while on single agent ibrutinib; EXCEPTION: patients may be on chronic steroids (maximum dose 20 mg/day prednisone equivalent) if they are being given for disorders other than amyloid, (i.e., adrenal insufficiency, rheumatoid arthritis, etc)
  • Active malignancy =< 3 years prior to registration; EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix; Note: if there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer
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  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Known history of human immunodeficiency virus (HIV) or active hepatitis C virus or active hepatitis B virus infection or any uncontrolled active systemic infection
  • Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk
  • Receiving any other investigational agent which would be considered as a treatment for AL amyloidosis
  • Vaccinated with live, attenuated vaccines =< 4 weeks prior to registration
  • Clinically overt multiple myeloma (i.e. original hypercalcemia, renal failure, anemia, bone lesions [CRAB] criteria); Note: extent of marrow plasmacytosis is not prohibitive
  • Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction =< 6 months prior to registration, or any class 3 (moderate) or class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
  • NT-ProBNP > 8,500 pg/mL
  • Use of strong and moderate CYP3A inhibitors and inducers =< 7 days prior to registration
  • Anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon); Note: use of low molecular weight heparin (or any anticoagulation agent) is allowed provided there is no history of bleeding (minor or major) =< 12 months prior to registration; the treating physician should discuss the case with the study chair
  • History of stroke or intracranial hemorrhage =< 6 months prior to registration
  • Known central nervous system metastasis
  • Major surgery or a wound that has not fully healed =< 4 weeks prior to registration
  • Surgery or invasive procedure requiring sutures or staples for closure =< 7 days prior to registration
  • Minor procedures (such as a central line placement, needle biopsy, thoracentesis, or paracentesis) =< 3 days prior to registration

About this study

Official title: Phase II Study of Ibrutinib With or Without Bortezomib and Dexamethasone for the Treatment of Patients With Relapsed/Refractory Immunoglobulin Light Chain Amyloidosis

This phase II trial studies how well ibrutinib with or without bortezomib and dexamethasone works in treating patients with immunoglobulin light chain amyloidosis that has come back after a period of improvement or that does not respond to treatment. Ibrutinib and bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ibrutinib with or without bortezomib and dexamethasone may work better in treating patients with relapsed or refractory immunoglobulin light chain amyloidosis.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the overall hematologic response rate (stringent complete response [sCR] + amyloid complete response [ACR]+ very good partial response [VGPR] + partial response [PR]) during the first 6 cycles for ibrutinib with bortezomib and dexamethasone added for lack of response in patients with amyloid light chain (AL).

SECONDARY OBJECTIVES:

  1. To evaluate overall hematologic response rate (sCR+ACR+VGPR+PR) of single agent ibrutinib in patients with AL.

II. To evaluate overall hematologic response rate (sCR+ACR+VGPR+PR) to ibrutinib + bortezomib and dexamethasone (Vd) in subjects with progressive disease after initial response to single agent ibrutinib.

III. To describe the toxicities associated with ibrutinib, alone and in combination with Vd, in patients with AL.

IV. To determine the organ response in AL patients treated with ibrutinib alone and in combination with Vd.

  1. To determine 3 year progression free survival of AL patients on the study.

TERTIARY OBJECTIVES:

  1. To characterize health related quality of life of patients. II. To determine the caregiver and patient disease burden. III. To determine the correlation between cardiac biomarkers and hematologic response to therapy.

IV. To evaluate the effect of ibrutinib on AL microenvironment. V. To characterize BTK expression in neoplastic plasma cells. VI. To evaluate the characterization of CD38 expression on neoplastic plasma cells.

OUTLINE:

Patients receive ibrutinib orally (PO) daily (QD) on days 1-28. After 3 courses, patients who achieve partial response repeat treatment every 28 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. Patients who do not achieve partial response after 3 courses continue receiving ibrutinib PO QD on days 1-28. Beginning at course 4, patients who do not achieve partial response also receive bortezomib subcutaneously (SC) and dexamethasone PO on days 1, 8, and 15. Treatment repeats every 28 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year, and then every 6 months for 2 years.

Being tested
Bortezomib, Dexamethasone, Ibrutinib, Laboratory Biomarker Analysis
Medical subject headings
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

  • DexamethasoneDrug

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

    Given PO

  • IbrutinibDrug

    Also called BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT03130348
Study groupRoleWhat they receive
Treatment (ibrutinib, bortezomib, dexamethasone)ExperimentalPatients receive ibrutinib PO QD on days 1-28. After 3 courses, patients who achieve partial response repeat treatment every 28 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. Patients who do not achieve partial response after 3 courses continue receiving ibrutinib PO QD on days 1-28. Beginning at course 4, patients who do not achieve partial response also receive bortezomib SC and dexamethasone PO on days 1, 8, and 15. Treatment repeats every 28 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Bortezomib; Drug: Dexamethasone; Drug: Ibrutinib; Other: Laboratory Biomarker Analysis

What is being measured

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

  1. Overall hematologic response rate during the first 6 courses for patients treated with ibrutinib, bortezomib, and dexamethasone

    Will include a confirmed stringent complete response, amyloid complete response, very good partial response, and partial response. Confirmation will be defined as a response that is maintained on two consecutive evaluations at least 2 weeks apart. Progression will be defined as either hematologic or organ progression. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.

    Measured: Up to 6 months

Secondary outcomes (4)

  1. Incidence of adverse events

    The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. Adverse events will be summarized separately for single agent Ibrutinib and combination therapy.

    Measured: Up to 3 years

  2. Organ response rate

    Will be estimated by the total number of patients who have an organ response divided by the total number of evaluable patients who had involvement in that organ at baseline. Exact binomial 95% confidence intervals for the true organ Up to response rate will be calculated.

    Measured: Up to 3 years

  3. Overall hematologic response rate for single agent ibrutinib

    Will be estimated by the total number of patients who achieve a partial response, very good partial response, stringent complete response, or amyloid complete response while receiving single agent ibrutinib divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true overall hematologic response rate will be calculated.

    Measured: Up to 6 months

  4. Progression-free survival

    Will be estimated using the method of Kaplan-Meier.

    Measured: From registration to the earliest date of documentation of disease progression (on single agent or combination therapy) or death due to any cause, assessed up to 3 years

Timeline

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

  1. First posted26 Apr 2017
  2. Study start15 Mar 2018 (estimated)
  3. Primary completionApr 2022 (estimated)
  4. Study completionApr 2022 (estimated)

Why it stopped: Study was dropped at site before participation

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03130348
Sponsor's protocol ID
MC1687
Other IDs
NCI-2017-00660, MC1687, P30CA015083
Status last verified
Feb 2018
First submitted
21 Apr 2017
Last updated
2 Mar 2018
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 2 study testing Bortezomib, Dexamethasone and Ibrutinib in people with Amyloidosis and Immunoglobulin Light Chain Deposition, run by Mayo Clinic.

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 21 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: withdrawn, as of the sponsor's last update on 2 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.

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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 was withdrawn before enrolling participants, so there are no results.

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?

Overall hematologic response rate during the first 6 courses for patients treated with ibrutinib, bortezomib, and dexamethasone (time frame: Up to 6 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 NCT03130348.

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 2 Mar 2018.

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