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

NCT ID: NCT02400437

Last Updated: 2020-09-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2019-11-30

Brief 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).

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.

Conditions

Waldenstrom's Macroglobulinemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IDR

• 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

Group Type: EXPERIMENTAL

Ixazomib

Intervention Type: DRUG

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

Dexamethasone

Intervention Type: DRUG

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

Rituximab

Intervention Type: DRUG

Doses given on Day 1 of induction and maintenance cycles.

Interventions

Ixazomib

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

Intervention Type: DRUG

Dexamethasone

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

Intervention Type: DRUG

Rituximab

Doses given on Day 1 of induction and maintenance cycles.

Intervention Type: DRUG

Other Intervention Names

MLN9708; Decadron; Dexasone,; Diodex; Hexadrol; Maxidex; Rituxan

Eligibility Criteria

Inclusion Criteria

• 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
• 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.

Exclusion Criteria

• 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.
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Jorge J. Castillo, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jorge J. Castillo, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 32822482 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29661775 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

14-559

Identifier Type: -

Identifier Source: org_study_id