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

NCT02400437 | Completed Phase 2 Results DMC

• 1 other identifier: 14-559
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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).

Conditions

Waldenstrom's Macroglobulinemia

Keywords

Waldenstrom's Macroglobulinemia

Outcome Measures

Primary Outcomes (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.

  76 weeks

Secondary Outcomes (6)

• Overall Response Rate

  2 Years

• Progression-free Survival (PFS)

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

• Overall Response Rate by MYD88 L265P and CXCR4-WHIM Status

  2 Years

• Time to Progression (TTP)

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

• Duration of Response (DOR)

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

Study Arms (1)

IDR

EXPERIMENTAL

\- 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

Drug: Ixazomib; Drug: Dexamethasone; Drug: Rituximab

Interventions

Ixazomib DRUG

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

Also known as: MLN9708

IDR

Dexamethasone DRUG

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

Also known as: Decadron, Dexasone,, Diodex, Hexadrol, Maxidex

IDR

Rituximab DRUG

Doses given on Day 1 of induction and maintenance cycles.

Also known as: Rituxan

IDR

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (2)

• 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.

  PMID: 32822482 DERIVED

• 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.

  PMID: 29661775 DERIVED

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

ixazomib; Dexamethasone; Calcium Dobesilate; Rituximab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Jorge Castillo
• Organization: Dana-Farber Cancer Institute

jorgej_castillo@dfci.harvard.edu

617-632-2681

Study Officials

• Jorge J. Castillo, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 10, 2015
• First Posted: March 27, 2015
• Study Start: April 1, 2015
• Primary Completion: November 1, 2019
• Study Completion: November 1, 2019
• Last Updated: September 2, 2020
• Results First Posted: September 2, 2020

Record last verified: 2020-08

Locations

US (1)