Zanubrutinib, Ixazomib and Dexamethasone in Patients With Treatment Naive Waldenstrom's Macroglobulinemia

NCT04463953 | Completed Phase 2 DMC

• 1 other identifier: IIT2020002
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate the efficacy of BTK inhibitor Zanubrutinib combined with Ixazomib and Dexamethasone (ZID) for the newly diagnosed Waldenstrom Macroglobulinemia. This ZID regimen will be given up to 24 months and stopped for observation. We propose this combination will improve the deep remission (≥VGPR) compared to single Zanubrutinib or IRD regimen and can be a time-limited regimen which will reduce the life-time therapy and benefit the patients.

Conditions

Waldenström Macroglobulinemia

Keywords

Waldenström Macroglobulinemia; Zanubrutinib; Ixazomib; Dexamethasone

Outcome Measures

Primary Outcomes (1)

• Deep remission response rate

  ≥VGPR after 6 cycles introduction

  up to 5 years

Secondary Outcomes (6)

• Complete response (CR)

  up to 12 months

• Progress-free survival (PFS)

  up to 5 years

• Duration of response (DoR)

  up to 5 years

• Overall survival (OS)

  up to 36 months

• Time to next treatment (TTNT)

  up to 5 years

Study Arms (1)

ZID regimen

EXPERIMENTAL

Zanubrutinib, 160mg orally, twice a day; Ixazomib, 4 mg orally, day 1, 8, 15; Dexamethasone, 20mg orally, days 1, 8, 15.

Drug: Zanubrutinib,Ixazomib and Dexamethasone

Interventions

Zanubrutinib,Ixazomib and Dexamethasone DRUG

Zanubrutinib, 160mg orally, twice a day; Ixazomib, 4 mg orally, day 1, 8, 15; Dexamethasone, 20mg orally, days 1, 8, 15；Ixazomib and dexamethasone every 4 weeks of a cycle, with induction of 6 cycles, and then maintain every 12 weeks, up to 6 cycles (96 cycles in total). Zanubrutinib is taken orally twice a day for up to 96 cycles, with a reduction in the last ID cycle. ZID regimen will continue 6 cycles after reaching the maximum response after introduction section.

ZID regimen

Eligibility Criteria

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

You may qualify if:

• The gender of the patient is not limited, and the age is ≥18 years old;
• Must meet WM's diagnostic standards;
• The patient is an untreated or patient who has not undergone standard treatment. The specific conditions are as follows:
• No combined chemotherapy with BR, RCD, VRD, CHOP and COP
• No treatment regimen containing fludarabine
• Chlorambucil or cyclophosphamide for less than 4 weeks (alone or in combination with adrenal glucocorticoids)
• The above treatment did not reach the treatment response (MR)
• If the above treatment has been applied, the treatment needs to be stopped for 2 weeks before entering the group to start treatment
• The indications for the treatment of indolent lymphoma mainly include (at least one of the following conditions):
• Symptomatic hyperviscosity;
• symptomatic peripheral neuropathy;
• Amyloidosis;
• Cold agglutinin disease; cryoglobulinemia;
• Disease-related cytopenia (Hb\<100 g/L, PLT\<100×10\^9/L);
• giant lymph nodes;

You may not qualify if:

• Malignant tumors (including active central nervous system lymphoma) other than B-NHL have been diagnosed or treated within the past year;
• There is clinical evidence that large cell lymphoma transformation has occurred;
• Non-lymphoma-related liver and kidney damage: alanine aminotransferase (ALT)\> 3 times the upper limit of normal value, aspartate aminotransferase (AST)\> 3 times the upper limit of normal value, total bilirubin (TBIL)\> upper limit of normal value 2 Times, serum creatinine clearance rate \<30ml/min;
• Other serious medical conditions will affect the study (such as uncontrolled diabetes, gastric ulcers, other serious cardiopulmonary diseases, etc.). The decision-making power belongs to the researcher;
• Known history of infection with human immunodeficiency virus (HIV) or active hepatitis B virus (HBV) infection, or any uncontrolled active systemic infection requiring intravenous antibiotics.
• Central nervous system dysfunction with clinical manifestations or central invasion (Bing-Neel syndrome);
• Patients who have undergone major surgery (not including lymph node biopsy) within the past 14 days or expected major surgery during treatment;
• Inability to swallow capsules or suffer from malabsorption syndrome, diseases that significantly affect gastrointestinal function, have undergone gastric or small bowel resection, symptomatic inflammatory bowel disease or ulcerative colitis, partial or complete intestinal obstruction.
• Need to receive strong cytochrome P450 (CYP) 3A inhibitor treatment.
• Women who are pregnant or breastfeeding, women of childbearing age who have not taken contraception;
• Allergy to the drugs used.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital

Tianjin, Tianjin Municipality, 300020, China

Location

Related Publications (3)

• Treon SP, Xu L, Guerrera ML, Jimenez C, Hunter ZR, Liu X, Demos M, Gustine J, Chan G, Munshi M, Tsakmaklis N, Chen JG, Kofides A, Sklavenitis-Pistofidis R, Bustoros M, Keezer A, Meid K, Patterson CJ, Sacco A, Roccaro A, Branagan AR, Yang G, Ghobrial IM, Castillo JJ. Genomic Landscape of Waldenstrom Macroglobulinemia and Its Impact on Treatment Strategies. J Clin Oncol. 2020 Apr 10;38(11):1198-1208. doi: 10.1200/JCO.19.02314. Epub 2020 Feb 21.

  PMID: 32083995 BACKGROUND

• Treon SP, Xu L, Hunter Z. MYD88 Mutations and Response to Ibrutinib in Waldenstrom's Macroglobulinemia. N Engl J Med. 2015 Aug 6;373(6):584-6. doi: 10.1056/NEJMc1506192. No abstract available.

  PMID: 26244327 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

zanubrutinib; ixazomib; Dexamethasone

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

Study Officials

• Shuhua Yi

  Chinese Academy of Medical Sciences and Peking Union Medical College

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Zanubrutinib, 160mg orally, twice a day; Ixazomib, 4 mg orally, day 1, 8, 15; Dexamethasone, 20mg orally, days 1, 8, 15.

Study Record Dates

• First Submitted: July 4, 2020
• First Posted: July 9, 2020
• Study Start: June 1, 2020
• Primary Completion: December 6, 2022
• Study Completion: December 6, 2022
• Last Updated: February 11, 2026

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)