Oral Azacitidine for Waldenstrom Macroglobulinemia

Phase-Based Estimates
1
Effectiveness
2
Safety
Trinity Health IHA Medical Group Hematology Oncology - Brighton, Brighton, MI
Waldenstrom Macroglobulinemia+27 More
Oral Azacitidine - Drug
Eligibility
65+
All Sexes
Eligible conditions
Waldenstrom Macroglobulinemia

Study Summary

This study is evaluating whether a combination of chemotherapy and oral azacitidine may help treat lymphoma.

See full description

Eligible Conditions

  • Waldenstrom Macroglobulinemia
  • Lymphoma, Follicular
  • Inflammation
  • Lymphoma, B-Cell
  • Lymphoma
  • Hodgkin Disease
  • Lymphoma, Large B-Cell, Diffuse
  • T-Cell/Histiocyte-Rich Large B-Cell Lymphoma
  • Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation
  • Diffuse Large B-Cell Lymphoma Germinal Center B-Cell Type
  • EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • Nodular Lymphocyte-Predominant Hodgkin's Lymphoma
  • Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type
  • Transformed Follicular Lymphoma to Diffuse Large B Cell Lymphoma
  • Intravascular Large B-Cell Lymphoma
  • High Grade B-Cell Lymphoma, Not Otherwise Specified
  • High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements
  • High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements
  • Lymphoplasmacytic Lymphoma
  • Ann Arbor Stage III Diffuse Large B-Cell Lymphoma
  • Diffuse Large B-Cell Lymphoma Activated B-Cell Type
  • Ann Arbor Stage IV Diffuse Large B-Cell Lymphoma
  • Ann Arbor Stage IIX (Bulky) Diffuse Large B-Cell Lymphoma
  • Transformed Marginal Zone Lymphoma to Diffuse Large B-Cell Lymphoma
  • Lymphoma, Follicular, Grade 3b
  • Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • HHV8-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements

Treatment Effectiveness

Effectiveness Estimate

1 of 3

Study Objectives

This trial is evaluating whether Oral Azacitidine will improve 2 primary outcomes, 3 secondary outcomes, and 3 other outcomes in patients with Waldenstrom Macroglobulinemia. Measurement will happen over the course of Baseline.

Baseline
Frailty status (fit/unfit vs frail) (Integrated Correlative Geriatric Assessments Substudy)
Year 5
Overall survival (Phase III)
Year 1
Progression-free survival (PFS) (Phase II)
Month 24
Changes in function (Integrated Correlative Geriatric Assessments Substudy)
Year 5
Incidence of adverse events
Month 24
Frailty status (Integrated Correlative Geriatric Assessments Substudy)
Up to completion of cycle 6
Excess toxicity as a result of adding oral azacitidine (CC-486) to reduced dose rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-miniCHOP) (Safety run-in)
Up to end of cycle 6 or end of treatment
Metabolic complete response (CR)

Trial Safety

Safety Estimate

2 of 3
This is better than 68% of similar trials

Trial Design

2 Treatment Groups

Arm II (R-miniCHOP)
Arm I (oral azacitidine, R-miniCHOP)

This trial requires 422 total participants across 2 different treatment groups

This trial involves 2 different treatments. Oral Azacitidine is the primary treatment being studied. Participants will all receive the same treatment. There is no placebo group. The treatments being tested are in Phase 2 & 3 and have had some early promising results.

Arm I (oral azacitidine, R-miniCHOP)Patients receive CC-486 PO for 7 days prior to cycle 1. Patients then receive CC-486 PO on days 8-21. Treatment repeats every 21 days for cycles 1-5 in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab IV (or SC for cycles 2-6), cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1, and prednisone PO on days 1-5. Treatment repeats every 21 days for cycles 1-6 (6 cycles total) in the absence of disease progression or unacceptable toxicity.
Arm II (R-miniCHOP)Patients receive rituximab IV (or SC for cycles 2-6), cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1, and prednisone PO on days 1-5. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Rituximab
FDA approved
Cortisone
Not yet FDA approved
Doxorubicin
FDA approved
Cyclophosphamide
FDA approved
Azacitidine
FDA approved
Vincristine
FDA approved

Trial Logistics

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: from date of registration to date of first observation of progressive disease according to the 2014 lugano classification, or death due to any cause, assessed up to 1 year
This trial has the following approximate timeline: 3 weeks for initial screening, variable treatment timelines, and roughly from date of registration to date of first observation of progressive disease according to the 2014 lugano classification, or death due to any cause, assessed up to 1 year for reporting.

Closest Location

Trinity Health IHA Medical Group Hematology Oncology - Brighton - Brighton, MI

Eligibility Criteria

This trial is for patients born any sex aged 65 and older. You must have received newly diagnosed for Waldenstrom Macroglobulinemia or one of the other 27 conditions listed above. There are 10 eligibility criteria to participate in this trial as listed below.

Mark “yes” if the following statements are true for you:
Participants must have histologically or cytologically confirmed diffuse large B-cell lymphoma (DLBCL), Ann Arbor Stage IIX (bulky), III or IV. Participants with DLBCL transformed from follicular lymphoma (FL) or marginal zone lymphoma (MZL, including mucosa-associated lymphoid tissue [MALT] lymphomas), lymphoplasmacytic lymphoma (LPL), or nodular lymphocyte-predominant Hodgkin Lymphoma (NLPHL) are eligible. Participants with Grade IIIB follicular lymphoma (FL) or high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements are also eligible. Participants with DLBCL that arose from prior CLL (Richter's transformation) are not eligible.
DLBCL, not otherwise specified (NOS)
DLBCL, germinal-center B-cell type (GCB)
DLBCL, activated B-cell type (ABC)
T-cell histiocyte-rich B-cell lymphomas (THRBCL)
Primary cutaneous DLBCL, leg type
Intravascular large B cell lymphoma
EBV+ DLBCL, NOS
DLBCL associated with chronic inflammation
HHV8+ DLBCL, NOS

Patient Q&A Section

Please Note: These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

What is the latest research for waldenstrom macroglobulinemia?

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Waldenström macroglobulinemia has many aspects that need to be studied further as knowledge of the disease increases. Results from a recent paper of this study have provided new information about the disease and treatment of waldenstrom macroglobulinemia.

Unverified Answer

Can waldenstrom macroglobulinemia be cured?

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Although the treatment of WM currently lacks a randomized, controlled, or prospective trial to prove its efficacy, we believe this article provides an acceptable rationale for treatment with ASCT or chemotherapy and autologous stem cell transplantation, which offers curative outcomes in carefully selected patients.

Unverified Answer

What are the signs of waldenstrom macroglobulinemia?

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Signs are similar to those shown in the general population and include low levels of platelets, anaemia and abnormal counts of cells. Other features include lytic bone lesions, high levels of cholesterol, low levels of immunoglobulins, and bone marrow hypereosinophilia.

Unverified Answer

Does waldenstrom macroglobulinemia run in families?

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We found no evidence that WM can be caused by a germ-line B-cell mutation. However, we found no evidence supporting either a rare or a sporadic germ-line etiology for WM.

Unverified Answer

What causes waldenstrom macroglobulinemia?

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Waldenström macroglobulinemia is a monoclonal plasma cell disease that most commonly presents with a plasma cell infiltrate in bone marrow that is positive for the kappa light chain. Our case is unusual in that it does not have a clonal IgM component. To our knowledge, this is one of the few cases of monoclonal plasma cell dyscrasia in which the cause of the plasma cell proliferation and bone marrow infiltration is idiopathic. We hypothesize that this plasma cell dyscrasia may represent a unique entity of plasma cell dyscrasia in that the plasma cell proliferation may be associated with a monoclonal IgT secretion to the blood.

Unverified Answer

What is waldenstrom macroglobulinemia?

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Waldenstrom macroglobulinemia, a rare circulating malignancy, is a systemic autoimmune disease causing persistent monoclonal plasma cell proliferation with minimal or mild bone marrow abnormalities. It is characterized by low-density (LD) IgM monoclonal plasma cells in blood and lymphoid tissues and has a unique clinical and pathological appearance.

Unverified Answer

How many people get waldenstrom macroglobulinemia a year in the United States?

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Around 20 to 30 percent of patients diagnosed with Waldenstroms disease in North America have a relapse. Further research as well as development of more effective treatment options would be of utmost importance for patients with Waldenstroms.

Unverified Answer

What are common treatments for waldenstrom macroglobulinemia?

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A variety of treatment options are currently used to treat waldenstrom macroglobulinemia. These options include surgery, radiation therapy to various parts of the body, chemotherapy, and/or targeted therapy with medications to treat the underlying disease. The prognosis for waldenstrom macroglobulinemia depends on the type and severity of the disease and is often determined by the cancer's stage at diagnosis.\n

Unverified Answer

How does oral azacitidine work?

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Toxicity, pharmacodynamics, and pharmacokinetics of oral azacitidine were well-characterized in the clinical trials. Azacitidine resulted in significant improvements in the management of MM. Additional studies with a less toxic dosing schedule and other myeloma therapies are warranted. There is also significant evidence to support the use of azacitidine as a second-line treatment of relapsed MM.

Unverified Answer

What are the common side effects of oral azacitidine?

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The main adverse events of AZA therapy are myelotoxicity, GI disturbances and fever/inflammation. The most common side effects were leukopenia, neutropenia and thrombocytopenia. All but one adverse event were mild.

Unverified Answer

What is the survival rate for waldenstrom macroglobulinemia?

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Survival for WM is very poor, with median survival only 10 years. Though death is often the presenting complaint, death from WM is rare. WM has a mortality rate around 2%.

Unverified Answer

Is oral azacitidine safe for people?

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Ondansetron and diphenhydramine was associated with significant and frequent vomiting. People with MM did not experience more significant vomiting. Azacitidine had no significant effect on QT intervals but a lower tendency towards more ventricular arrhythmias in people with MM. Clinicians prescribing oral azacitidine should be aware of this risk.

Unverified Answer
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