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Waldenstrom's MacroglobulinemiaPhase 2NCT02400437

Trial of Ixazomib, Dexamethasone and Rituximab in Patients With Untreated Waldenstrom's Macroglobulinemia

A Phase 2 study testing Ixazomib, Dexamethasone and Rituximab in people with Waldenstrom's Macroglobulinemia, run by Dana-Farber Cancer Institute 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 research study is evaluating a drug called ixazomib (also known as MLN9708) in combination with dexamethasone and rituximab (the regimen is called IDR) as a possible treatment for Waldenstrom's Macroglobulinemia (WM). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Waldenstrom's Macroglobulinemia
What is being tested?
Ixazomib, Dexamethasone and Rituximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
1 siteUnited States
Study dates
Apr 2015to Nov 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Male or female patients 18 years or older.
  • Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that the patient may withdraw consent 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, AND
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  • 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.)
  • Clinicopathological diagnosis of WM (Owen 2003), with symptomatic disease meeting criteria for treatment using consensus panel criteria from the Second International Workshop on WM (Kyle 2003), and measurable disease, defined as presence of immunoglobulin M (IgM) paraprotein with a minimum IgM level of >2 times the upper limit of normal.
  • Eastern Cooperative Oncology Group performance status of 0, 1, or 2.
  • Patients must meet the following clinical laboratory criteria
  • Absolute neutrophil count ≥1,000/mm3 and platelet count ≥75,000/mm3. 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 ≥30 mL/min.

Who cannot join

  • Female patients who are lactating or have a positive serum pregnancy test during the screening period.
  • Major surgery within 14 days before enrollment.
  • Central nervous system involvement.
  • Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment.
  • Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
  • Systemic treatment, within 14 days before the first dose, with strong inhibitors of cytochrome P (CYP) 1A2, strong inhibitors of CYP3A, or strong CYP3A inducers, or use of Ginkgo biloba or St. John's wort.
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  • Known hepatitis B or C virus, or HIV infection.
  • 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 non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

Other trials in United States

About this study

Official title: Phase II Trial of Ixazomib, Dexamethasone and Rituximab in Patients With Untreated Waldenstrom's Macroglobulinemia

This research study is evaluating a drug called ixazomib (also known as MLN9708) in combination with dexamethasone and rituximab (the regimen is called IDR) as a possible treatment for Waldenstrom's Macroglobulinemia (WM).

Read the detailed description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational regimen, IDR, to learn whether IDR works in treating a specific cancer. "Investigational" means that IDR is still being studied and that research doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause, and if IDR is effective for treating different types of cancer. It also means that the FDA (the U.S. Food and Drug Administration) has not yet approved IDR for use in participants with your type of cancer.

Ixazomib is a drug that may kill or stop cancer cells from growing by blocking the proteasome within the cell, which is responsible for degrading or breaking down a variety of proteins. This type of drug is called a proteasome inhibitor.

Rituximab is a type of protein called an antibody that attacks the cluster of differentiation 20 (CD20), a protein found on B-cells like WM. Rituximab is approved by the FDA for treating non-Hodgkin lymphoma (NHL). Dexamethasone is a steroid and is similar to the hormones naturally produced by the adrenal glands; it prevents the release of substances that cause inflammation. Rituximab and dexamethasone are often used to treat WM, alone or in combination with other drugs. Combinations with rituximab, dexamethasone and other proteasome inhibitors have shown good response rates in WM participants. Ixazomib is a proteasome inhibitor; thus the investigator swill investigate if the combination of Ixazomib, Rituximab, and Dexamethasone is also active in WM.

In this research study, the investigators are combining a new treatment ixazomib with a standard regimen, rituximab and dexamethasone, to determine whether this combination (IDR) is effective and safe for participants with previously untreated WM.

Being tested
Ixazomib, Dexamethasone, Rituximab
Keywords
Waldenstrom's Macroglobulinemia
Medical subject headings
Waldenstrom Macroglobulinemia

What participants receive

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

  • IxazomibDrug

    Also called MLN9708

    Doses given on Days 1, 8, and 15 in induction and maintenance cycles.

  • DexamethasoneDrug

    Also called Decadron, Dexasone,, Diodex, Hexadrol

    Doses given on Days 1, 8, and 15 in induction and maintenance cycles.

  • RituximabDrug

    Also called Rituxan

    Doses given on Day 1 of induction and maintenance cycles.

Study groups in NCT02400437
Study groupRoleWhat they receive
IDRExperimental- IDR The study treatment will consist on an induction and a maintenance phase. Dose modification will be permitted for toxicity * Induction cycles will be 4 weeks long, Maintenance cycles 8 weeks long. * Ixazomib- administered orally on predetermined days and dosage during Induction and Maintenance Phase * Dexamethasone- administered via IV or orally on predetermined days and dosage during Induction and Maintenance Phase * Rituximab- administered via IV on predetermined days and dosage during Induction and Maintenance Phase
Receives: Drug: Ixazomib; Drug: Dexamethasone; Drug: Rituximab

What is being measured

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

  1. Very Good Partial Response Rate (VGPR) for IDR

    Rate of very good partial response or better in patients treated with IDR. VGPR is defined as a >90% reduction in serum IgM levels from baseline.

    Measured: 76 weeks

Secondary outcomes (6)

  1. Overall Response Rate

    Overall response includes the rate of complete response (CR), partial response (PR), minimal response (MR), stabl disease (SD) and progressive disease (PD). Minor response is >25%-50% reduction in serum IgM from baseline. Partial Response is (>50-90% reduction in serum IgM from baseline. Very Good Partial Response is >90% reduction in serum IgM from baseline. Complete Response is resolution of all symptoms, normalization of serum IgM with disappearance of IgM paraprotein, resolution of any adenopathy or splenomegaly.

    Measured: 2 Years

  2. Progression-free Survival (PFS)

    Duration of time from start of treatment to disease progression. Progressive disease is defined as occurring when a >25% increase in serum IgM and an absolute 500mg/dL increase in IgM level occurs from the lowest attained response value, or progression of clinically significant disease related symptoms.

    Measured: From start of treatment to time of disease progression, assessed up to 4 years after treatment start

  3. Overall Response Rate by MYD88 L265P and CXCR4-WHIM Status

    To evaluate the overall response rate of participants by MYD88 L265P and CXCR4-WHIM mutations in WM. Overall response is defined as achieving at least a minor response, or >25% reduction in serum IgM from baseline.

    Measured: 2 Years

  4. Time to Progression (TTP)

    Duration of time from start of treatment to time of disease progression.

    Measured: From start of treatment to time of disease progression, assessed up to 4 years after treatment start

  5. Duration of Response (DOR)

    The duration of response is measured from the time a participant achieved a response until the date of progression.

    Measured: From the time each participant achieved a response to time of disease progression, assessed up to 4 years after treatment start

  6. Time to Next Therapy (TTNT)

    Duration from start of protocol treatment to time of initiation of new therapy.

    Measured: From start of treatment until the participant begins a new therapy, assessed up to 4 years after treatment start

Timeline

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

  1. First posted27 Mar 2015 (estimated)
  2. Study startApr 2015
  3. Primary completionNov 2019
  4. Study completionNov 2019

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
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02400437
Sponsor's protocol ID
14-559
Status last verified
Aug 2020
First submitted
10 Mar 2015
Last updated
2 Sep 2020
Data monitoring committee
Yes

Publications

  • Castillo JJ, Meid K, Flynn CA, Chen J, Demos MG, Guerrera ML, Kofides A, Liu X, Munshi M, Tsakmaklis N, Patterson CJ, Yang G, Hunter Z, Treon SP. Ixazomib, dexamethasone, and rituximab in treatment-naive patients with Waldenstrom macroglobulinemia: long-term follow-up. Blood Adv. 2020 Aug 25;4(16):3952-3959. doi: 10.1182/bloodadvances.2020001963.

    PubMed 32822482

  • Castillo JJ, Meid K, Gustine JN, Dubeau T, Severns P, Hunter ZR, Yang G, Xu L, Treon SP. Prospective Clinical Trial of Ixazomib, Dexamethasone, and Rituximab as Primary Therapy in Waldenstrom Macroglobulinemia. Clin Cancer Res. 2018 Jul 15;24(14):3247-3252. doi: 10.1158/1078-0432.CCR-18-0152. Epub 2018 Apr 16.

    PubMed 29661775

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ixazomib, Dexamethasone and Rituximab in people with Waldenstrom's Macroglobulinemia, run by Dana-Farber Cancer Institute 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 17 inclusion and 12 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 2 Sep 2020. 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 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?

Yes. Results are posted in the registry (first posted 2 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Very Good Partial Response Rate (VGPR) for IDR (time frame: 76 weeks). 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 NCT02400437, which also lists 2 linked publications.

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 Sep 2020.

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