IgM MGUSPhase 2NCT05065554
ACALA-R In Predominantly Demyelinating IgM Mediated Neuropathy
A Phase 2 study testing Acalabrutinib and Rituximab in people with IgM MGUS and Waldenstrom Macroglobulinemia, run by Shayna Sarosiek, MD at 2 sites in United States.
Trial summary
In this research study, is combining a new treatment acalabrutinib with a standard treatment, rituximab or other CD20 antibody, to determine whether this combination is safe and effective for participants with Immunoglobulin (Ig) M monoclonal gammopathy of undetermined significance ( IgM MGUS) or Waldenström… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- IgM MGUS, Waldenstrom Macroglobulinemia, Neuropathy;Peripheral
- What is being tested?
- Acalabrutinib and Rituximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 2 sitesUnited States
- Study dates
- 16 Nov 2021to 1 Oct 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Participants must meet the following criteria on screening examination to be eligible to participate. Screening evaluations including consent, physical exam, and laboratory assessments will be done within 30 days prior to Cycle 1 Day 1. Bone marrow biopsy \&aspirate, skin (fat) biopsy, EMG, and CT C/A/P will be done within 90 days prior to Cycle1 Day 1.
- Presence of an IgM monoclonal paraprotein on serum immunofixation electrophoresis
- Diagnosis of IgM MGUS or Waldenstrӧm macroglobulinemia using the criteria from Owen RG, Treon SP, Al-Katib A, Fonseca R, Greipp PR, McMaster ML, et al.Clinicopathological definition of Waldenstrom's macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia. Semin Oncol. 2003. 30(2): 110-5.
- WM diagnostic criteria
- IgM monoclonal gammopathy of any concentration
- Bone marrow infiltration by small lymphocytes showing plasmacytoid/plasma cell differentiation
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- Intertrabecular pattern of bone marrow infiltration
- Surface IgM+, CD5 +/-, CD10-, CD19+, CD20+, CD22+, CD23-, CD25+, CD27+, FMC7+, CD103-, CD138- immunophenotype* --- Variations from this immunophenotypic profile can occur. However, care should be taken to satisfactorily exclude other lymphoproliferative disorders. This is most relevant in CD5+ cases, for which chronic lymphocytic leukemia and mantle cell lymphoma require specific exclusion before a diagnosis of WM can be made.
- IgM MGUS diagnostic criteria
- IgM monoclonal gammopathy of any concentration
- No bone marrow infiltration
- Presence of predominantly sensory neuropathy with predominant demyelinating features on nerve conduction studies.
- Modified Rankin Scale score of ≥1 with progressing symptoms or a score ≥2
- ECOG ≤2
- Age > 18 years
- Participants may not be on any active therapy for other malignancies with the exception of topical therapies for basal cell or squamous cell cancers of the skin
- At the time of screening, participants must have acceptable organ and marrow function as defined below:
- Absolute neutrophil count≥1,000/uL (no growth factor permitted within previous 7 days)
- Platelets ≥100,000/uL (no platelet transfusions permitted within previous 7 days); patients may enroll below this threshold if not attributable to IgM MGUS or WM after consultation with Sponsor-Investigator.
- For participants with platelets <100,000 uL deemed to be attributable to other causes than IgM MGUS or WM, platelets must be ≥50,000 uL (no platelet transfusions permitted)
- Hemoglobin ≥ 10 g/dL (transfusions permitted); patients may enroll below this threshold if not attributable to IgM MGUS or WM after consultation with Sponsor-Investigator.
- -- For participants with hemoglobin <10 g/dL deemed to be attributable to other causes than IgM MGUS or WM, hemoglobin must be ≥7 g/dL(transfusions permitted)
- Total bilirubin < 1.5 x institutional ULN
- AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN
- Estimated GFR ≥30 mL/min
- International normalized ratio (INR) ≤ 2 x ULN and activated partial thromboplastin time (aPTT) ≤ 2 x ULN. Patients with INR and/or aPTT >2 x ULN who have lupus anticoagulant may be enrolled.
- Females of childbearing potential (FCBP) must use highly effective contraception (see Appendix D) or have complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) while participating in the study; and 2) for at least 1 week after last dose of acalabrutinib and 12 months from last dose of rituximab/biosimilar. FCBP must be referred to a qualified provider of contraceptive methods if needed. FCBP must have a negative serum pregnancy test at screening.
- Men must agree to use a latex condom during treatment and for up to 1 week after the last dose of acalabrutinib and 12 months after the last dose of rituximab during sexual contact with a FCBP
- Ability to adhere to the study visit schedule and other protocol requirements
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study:
- Serum IgM ≥4,000 mg/dL
- Waldenstrӧm macroglobulinemia meeting criteria for treatment using consensus panel criteria from the Second International Workshop on WM besides symptomatic peripheral neuropathy.
- Prior exposure to chemotherapy, BTK inhibitors or other therapies used for WM treatment, except steroids, IVIG, or anti-CD20 antibodies that were administered >90 days prior to first dose of study drug
- Concurrent participation in another therapeutic clinical trial.
- Participants with marginal zone lymphoma (MZL), chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), IgM Myeloma or AL amyloidosis are excluded (Diagnosis based on WHO Classification of Tumours of Hematopoietic and Lymphoid Tissues, S.H. Swerdlow, et al., Editors. 2017, IARC)
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- Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP)
- Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months prior to screening
- Prior hypersensitivity, anaphylaxis, or intolerance to rituximab/biosimilar and ofatumumab, or acalabrutinib, including active product or excipient components
- Vaccination with a live vaccine within 4 weeks prior to first dose of rituximab.
- Prior or concurrent active malignancy within the past 2 years, except for curatively treated basal or squamous cell skin cancer, carcinoma in situ of the cervix or breast, or localized prostate cancer.
- Any condition, including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study
- Known history of neuropathy attributed to an etiology other than IgM-mediated neuropathy
- Concurrent administration of medications that are moderate or strong inhibitors or inducers of CYP3A within 7 days prior to first dose of study drug
- Current, ongoing daily use of a proton pump inhibitor. Participants who switch to H2- receptor antagonists or antacids are eligible.
- Participants with chronic liver disease and hepatic impairment meeting Child-Pugh class C
- Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists
- Peripheral neuropathy symptoms that have been present for >5 years
- Known central nervous system lymphoma
- Active bleeding or history of bleeding diathesis (e.g., congenital von Willebrand's disease or hemophilia)
- History of significant cerebrovascular disease/event, including stroke or intracranial hemorrhage, within 6 months prior to the first dose of study drug
- Major surgery within 4 weeks of first dose of study drug
- Malabsorption syndrome or other condition that precludes enteral route of administration
- Female participants who are pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 1 week of last dose of study drug acalabrutinib, or 12 months of last dose of rituximab/biosimilar.
- Male participants who plan to father a child while enrolled in this study or within 90 days after the last dose of study drug
- Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening
- New York Heart Association classification III or IV heart failure
- No active Human Immunodeficiency Virus (HIV) infection
- Active infection with Hepatitis B virus (HBV) or viral hepatitis C (HCV) as follows:
- Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Note: Patients with presence of HBcAb, but absence of HBsAg, are eligible if HBV DNA is undetectable and if they are willing to undergo monitoring for HBV reactivation throughout the study.
- Patients with presence of HCV antibody are eligible if HCV RNA is undetectable and if they are willing to undergo monitoring for HCV reactivation.
- No significant infection (eg bacterial, viral, or fungal) at study entry
- Inability to swallow pills
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Unwillingness or inability to comply with the protocol
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital
Boston, Massachusetts, 02214
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
About this study
Official title: Phase II Study on Acalabrutinib and Anti-CD20 Antibody in Patients With Predominantly Demyelinating Neuropathy With or Without Anti-MAG
In this research study, is combining a new treatment acalabrutinib with a standard treatment, rituximab or other CD20 antibody, to determine whether this combination is safe and effective for participants with Immunoglobulin (Ig) M monoclonal gammopathy of undetermined significance ( IgM MGUS) or Waldenström macroglobulinemia WM related neuropathies.
The names of the study drugs involved in this study are/is:
- Acalabrutinib
- Rituximab or similar CD20 antibody
Read the detailed description
This research study involves an experimental drug combination of a targeted therapy and a CD20 antibody.
The names of the study drugs involved in this study are/is:
- Acalabrutinib
- Rituximab or similar CD20 antibody
The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.
The study treatment for up to 4 years and will be followed for 2 years after completion of study treatment.
It is expected that about 33 people will take part in this research study.
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.
The U.S. Food and Drug Administration (FDA) has not approved acalabrutinib for this specific disease but it has been approved for other uses.
The U.S. Food and Drug Administration (FDA) has not approved rituximab or similar CD20 antibody for this specific disease but it has been approved for other uses.
- Acalabrutinib is a targeted therapy that blocks a type of protein called Bruton Tyrosine Kinase (BTK) that helps cells live and grow. By blocking BTK, acalabrutinib may kill abnormal cells or stop them from growing. It has been FDA approved for mantle cell lymphoma (MCL).
- Rituximab, or biosimilar, is a type of therapy called an antibody that attacks CD20, a protein found on B-cells. Rituximab is approved by the FDA for treating non-Hodgkin lymphoma (NHL). Rituximab is often used to treat WM and IgM MGUS neuropathies. Biosimilars are FDA approved drugs that have been determined to be interchangeable with the original drug.
- Being tested
- Acalabrutinib, Rituximab
- Keywords
- IgM MGUS, Waldenstrom Macroglobulinemia
- Medical subject headings
- Waldenstrom Macroglobulinemia, Neuritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcalabrutinibDrug
Also called Calquence
Dose per protocol, oral twice daily per cycle
RituximabDrug
Also called Rituxan
Premedications (including acetaminophen, an antihistamine, and a steroid) will be given per institutional guideline Dosage determined per protocol and cycle timepoint, Route IV or SQ per protocol and cycle timepoint, schedule per protocol and cycle timepoint
| Study group | Role | What they receive |
|---|---|---|
| ACALABRUTINIB + RITUXIMAB/BIOSIMILAR | Experimental | Acalabrutinib and rituximab (or biosimilar) with be contained in the treatment regimen.
Acalabrutinib will be administered twice daily, with 28 consecutive days defined as a treatment cycle. Acalabrutinib will be administered for 48 cycles or until disease progression or unacceptable toxicity.
Rituximab will be administered on Days 1, 8, 15, and 22 of Cycles 1 and 4. Participants will have study visits every cycle for cycles 1-6, then every 3 cycles, with the next visit at Cycle 9, then C12, C15, etc.
Participants will continue acalabrutinib until disease progression or intolerable adverse effect develops. They will be followed for up to 2 years after completion of 48 cycles of treatment or until death Receives: Drug: Acalabrutinib; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall hematologic response rate
defined as ≥25% reduction in serum IgM) during treatment compared to baseline in patients with IgM mediated symptomatic neuropathy treated with the combination acalabrutinib + rituximab (or biosimilar
Measured: baseline to 6 years
Secondary outcomes (18)
Progression Free Survival
Time from initiation of Acalabrutinib + rituximab therapy until disease progression (>25% increase in serum IgM and 500 mg/dL absolute increase).
Measured: Duration of time from start of treatment to time of objective disease progression (including initiation of new therapy or death) up to 6 years
Time to next treatment
Time from initiation of Acalabrutinib + rituximab therapy until initiation of new line of therapy
Measured: Duration of time from start of treatment to next therapy or last follow-up up to 72 months
Overall Survival
Time from initiation of therapy until death
Measured: Duration of time from start of treatment to time of death or last follow-up up to 72 months
Complete Response Rate
Proportion of patients with a complete response. Complete response (CR) is defined as having resolution of WM related symptoms, normalization of serum IgM levels with complete disappearance of IgM paraprotein by immunofixation, and resolution of any adenopathy or splenomegaly. A complete response requires reconfirmation demonstrating normal serum IgM levels, and absence of IgM paraprotein by immunofixation by a measurement repeated at least 2 weeks later.
Measured: Duration of time from start of treatment to last follow-up up to 72 months.
Bone marrow response
Absolute change in bone marrow burden of disease from baseline in patients who have involvement at baseline.
Measured: Cycle 12, yearly up to 4 years
Number of Participants to Treatment Related Adverse Events
NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Measured: Throughout the study and for 30 days after the last dose, up 4 years
Very Good Partial Response (VGPR):
Proportion of patients with a very good partial response (VGPR) defined as >90% reduction in serum IgM levels, or normalization of serum IgM levels with persistent IgM monoclonal spike in SPEP or immunofixation.
Measured: Duration of time from start of treatment to last follow-up up to 72 months.
Partial Response (PR):
Proportion of patients with a Partial response (PR) is defined as achieving a >50% reduction in serum IgM levels.
Measured: Duration of time from start of treatment to last follow-up up to 72 months.
Minor Response (MR):
Proportion of patients with a minor response (MR) is defined 25-49% reduction in serum IgM levels.
Measured: Duration of time from start of treatment to last follow-up up to 72 months.
Rate of neuropathy response by INCAT-ISS
The proportion of patients with improvement or stability in neuropathy based on INCAT-ISS
Measured: Cycles 3, 6, 9, 12 (each cycle is 28 days), and then yearly for the duration of the study up to 6 Years
Rate of neuropathy response by INCAT disability score
The proportion of patients with improvement or stability in neuropathy based on INCAT disability score
Measured: Cycles 3, 6, 9, 12 (each cycle is 28 days), and then yearly for the duration of the study up to 6 Years
Rate of neuropathy response by MRC distal sum score
The proportion of patients with improvement or stability in neuropathy based on MRC distal sum score
Measured: Cycles 3, 6, 9, 12 (each cycle is 28 days), and then yearly for the duration of the study up to 6 Years
Rate of neuropathy response by 10-meter walk time
The proportion of patients with improvement or stability in neuropathy based on 10-meter walk time changes.
Measured: Cycles 3, 6, 9, 12 (each cycle is 28 days), and then yearly for the duration of the study up to 6 Years
Rate of neuropathy response by 9-hole peg test
The proportion of patients with improvement or stability in neuropathy based on 9-hole peg test.
Measured: Cycles 3, 6, 9, 12 (each cycle is 28 days), and then yearly for the duration of the study up to 6 Years
Rate of neuropathy response by VAS
The proportion of patients with improvement or stability in neuropathy based on Visual Analogue Scale.
Measured: Cycles 3, 6, 9, 12 (each cycle is 28 days), and then yearly for the duration of the study up to 6 Years
Rate of neuropathy response by I-RODS functional score
The proportion of patients with improvement or stability in neuropathy based on I-RODS functional score
Measured: Cycles 3, 6, 9, 12 (each cycle is 28 days), and then yearly for the duration of the study up to 6 Years
Rate of neuropathy response by Rausch built FSS
The proportion of patients with improvement or stability in neuropathy based on Rausch built Fatigue Severity Score
Measured: Cycles 3, 6, 9, 12 (each cycle is 28 days), and then yearly for the duration of the study up to 6 Years
Rate of neuropathy response by IN-QOL tool
The proportion of patients with improvement or stability in neuropathy based on IN-QOL tool
Measured: Cycles 3, 6, 9, 12 (each cycle is 28 days), and then yearly for the duration of the study up to 6 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2021
- Study start16 Nov 2021
- Primary completion1 Dec 2026 (estimated)
- Study completion1 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for IgM MGUSStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shayna Sarosiek, MD
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor-investigator, Shayna Sarosiek, MD, Dana-Farber Cancer Institute
- Investigators
- Shayna R. Sarosiek, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05065554
- Sponsor's protocol ID
- 21-439
- Status last verified
- Dec 2025
- First submitted
- 20 Sep 2021
- Last updated
- 5 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Publications
Nardin J, Dittus C, Traub R. Clinical and Electrodiagnostic Findings in Anti-myelin-Associated Glycoprotein Antibody Polyneuropathy: A Single Center Review. J Clin Neuromuscul Dis. 2025 Jun 2;26(4):200-205. doi: 10.1097/CND.0000000000000525.
PubMed 40513035
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study on Acalabrutinib and Anti-CD20 Antibody in Patients With Predominantly Demyelinating Neuropathy With or Without Anti-MAG
- ClinicalTrials.gov ID
- NCT05065554
- Acronym / sponsor ID
- 21-439
- Keywords
- IgM MGUS, Waldenstrom Macroglobulinemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Shayna Sarosiek, MDUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- 16 Nov 2021 (actual)
- Primary completion
- 1 Dec 2026 (estimated)
- Study completion
- 1 Oct 2028 (estimated)
- First posted
- 4 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this research study, is combining a new treatment acalabrutinib with a standard treatment, rituximab or other CD20 antibody, to determine whether this combination is safe and effective for participants with Immunoglobulin (Ig) M monoclonal gammopathy of undetermined significance ( IgM MGUS) or Waldenström macroglobulinemia WM related neuropathies.
The names of the study drugs involved in this study are/is:
- Acalabrutinib
- Rituximab or similar CD20 antibody
Detailed description
This research study involves an experimental drug combination of a targeted therapy and a CD20 antibody.
The names of the study drugs involved in this study are/is:
- Acalabrutinib
- Rituximab or similar CD20 antibody
The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.
The study treatment for up to 4 years and will be followed for 2 years after completion of study treatment.
It is expected that about 33 people will take part in this research study.
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.
The U.S. Food and Drug Administration (FDA) has not approved acalabrutinib for this specific disease but it has been approved for other uses.
The U.S. Food and Drug Administration (FDA) has not approved rituximab or similar CD20 antibody for this specific disease but it has been approved for other uses.
- Acalabrutinib is a targeted therapy that blocks a type of protein called Bruton Tyrosine Kinase (BTK) that helps cells live and grow. By blocking BTK, acalabrutinib may kill abnormal cells or stop them from growing. It has been FDA approved for mantle cell lymphoma (MCL).
- Rituximab, or biosimilar, is a type of therapy called an antibody that attacks CD20, a protein found on B-cells. Rituximab is approved by the FDA for treating non-Hodgkin lymphoma (NHL). Rituximab is often used to treat WM and IgM MGUS neuropathies. Biosimilars are FDA approved drugs that have been determined to be interchangeable with the original drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ACALABRUTINIB + RITUXIMAB/BIOSIMILAR | Experimental | Drug: Acalabrutinib, Drug: RituximabAcalabrutinib and rituximab (or biosimilar) with be contained in the treatment regimen. Acalabrutinib will be administered twice daily, with 28 consecutive days defined as a treatment cycle. Acalabrutinib will be administered for 48 cycles or until disease progression or unacceptable toxicity. Rituximab will be administered on Days 1, 8, 15, and 22 of Cycles 1 and 4. Participants will have study visits every cycle for cycles 1-6, then every 3 cycles, with the next visit at Cycle 9, then C12, C15, etc. Participants will continue acalabrutinib until disease progression or intolerable adverse effect develops. They will be followed for up to 2 years after completion of 48 cycles of treatment or until death |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- Participants must meet the following criteria on screening examination to be eligible to participate. Screening evaluations including consent, physical exam, and laboratory assessments will be done within 30 days prior to Cycle 1 Day 1. Bone marrow biopsy \&aspirate, skin (fat) biopsy, EMG, and CT C/A/P will be done within 90 days prior to Cycle1 Day 1.
- Presence of an IgM monoclonal paraprotein on serum immunofixation electrophoresis
- Diagnosis of IgM MGUS or Waldenstrӧm macroglobulinemia using the criteria from Owen RG, Treon SP, Al-Katib A, Fonseca R, Greipp PR, McMaster ML, et al.Clinicopathological definition of Waldenstrom's macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia. Semin Oncol. 2003. 30(2): 110-5.
- IgM MGUS diagnostic criteria
- Presence of predominantly sensory neuropathy with predominant demyelinating features on nerve conduction studies.
Key exclusion criteria (35 listed)
- Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study:
- Serum IgM ≥4,000 mg/dL
- Waldenstrӧm macroglobulinemia meeting criteria for treatment using consensus panel criteria from the Second International Workshop on WM besides symptomatic peripheral neuropathy.
- Prior exposure to chemotherapy, BTK inhibitors or other therapies used for WM treatment, except steroids, IVIG, or anti-CD20 antibodies that were administered >90 days prior to first dose of study drug
- Concurrent participation in another therapeutic clinical trial.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AcalabrutinibAlso: CalquenceDose per protocol, oral twice daily per cycle | Drug | ACALABRUTINIB + RITUXIMAB/BIOSIMILAR |
| RituximabAlso: RituxanPremedications (including acetaminophen, an antihistamine, and a steroid) will be given per institutional guideline Dosage determined per protocol and cycle timepoint, Route IV or SQ per protocol and cycle timepoint, schedule per protocol and cycle timepoint | Drug | ACALABRUTINIB + RITUXIMAB/BIOSIMILAR |
Primary outcome
Overall hematologic response rate
Time frame: baseline to 6 years
defined as ≥25% reduction in serum IgM) during treatment compared to baseline in patients with IgM mediated symptomatic neuropathy treated with the combination acalabrutinib + rituximab (or biosimilar
18 secondary outcomes
Progression Free Survival
Time frame: Duration of time from start of treatment to time of objective disease progression (including initiation of new therapy or death) up to 6 years
Time to next treatment
Time frame: Duration of time from start of treatment to next therapy or last follow-up up to 72 months
Overall Survival
Time frame: Duration of time from start of treatment to time of death or last follow-up up to 72 months
Complete Response Rate
Time frame: Duration of time from start of treatment to last follow-up up to 72 months.
Bone marrow response
Time frame: Cycle 12, yearly up to 4 years
Number of Participants to Treatment Related Adverse Events
Time frame: Throughout the study and for 30 days after the last dose, up 4 years
Very Good Partial Response (VGPR):
Time frame: Duration of time from start of treatment to last follow-up up to 72 months.
Partial Response (PR):
Time frame: Duration of time from start of treatment to last follow-up up to 72 months.
Minor Response (MR):
Time frame: Duration of time from start of treatment to last follow-up up to 72 months.
Rate of neuropathy response by INCAT-ISS
Time frame: Cycles 3, 6, 9, 12 (each cycle is 28 days), and then yearly for the duration of the study up to 6 Years
Rate of neuropathy response by INCAT disability score
Time frame: Cycles 3, 6, 9, 12 (each cycle is 28 days), and then yearly for the duration of the study up to 6 Years
Rate of neuropathy response by MRC distal sum score
Time frame: Cycles 3, 6, 9, 12 (each cycle is 28 days), and then yearly for the duration of the study up to 6 Years
Rate of neuropathy response by 10-meter walk time
Time frame: Cycles 3, 6, 9, 12 (each cycle is 28 days), and then yearly for the duration of the study up to 6 Years
Rate of neuropathy response by 9-hole peg test
Time frame: Cycles 3, 6, 9, 12 (each cycle is 28 days), and then yearly for the duration of the study up to 6 Years
Rate of neuropathy response by VAS
Time frame: Cycles 3, 6, 9, 12 (each cycle is 28 days), and then yearly for the duration of the study up to 6 Years
Rate of neuropathy response by I-RODS functional score
Time frame: Cycles 3, 6, 9, 12 (each cycle is 28 days), and then yearly for the duration of the study up to 6 Years
Rate of neuropathy response by Rausch built FSS
Time frame: Cycles 3, 6, 9, 12 (each cycle is 28 days), and then yearly for the duration of the study up to 6 Years
Rate of neuropathy response by IN-QOL tool
Time frame: Cycles 3, 6, 9, 12 (each cycle is 28 days), and then yearly for the duration of the study up to 6 Years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2025.
- Derived from this study: PubMed 40513035Nardin J, Dittus C, Traub R. Clinical and Electrodiagnostic Findings in Anti-myelin-Associated Glycoprotein Antibody Polyneuropathy: A Single Center Review. J Clin Neuromuscul Dis. 2025 Jun 2;26(4):200-205. doi: 10.1097/CND.0000000000000525.
- Individual participant dataSharing planned: Yes. The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
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Monoclonal Gammopathy of Undetermined Significance (MGUS), Smoldering Multiple Myeloma (SMM)
Active, not recruitingPhase 2
Zanubrutinib Treatment in Patients With IgM Monoclonal Gammopathy and Antri-MAG Related Polyneuropathy
Monoclonal Gammopathy of Uncertain Significance
RecruitingObservational study
Spanish Registry of Patients With IgM Monoclonal Gammopathies
Waldenstrom Macroglobulinemia
Enrolling by invitationObservational study
A Study of Carbon 13-based Deep Labelling of Bone Marrow Cells
Monoclonal Gammopathy of Undetermined Significance (MGUS), Non-IgM Monoclonal Gammopathy of Undetermined Significance
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shayna R. Sarosiek, MD principal investigator
Dana-Farber Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Acalabrutinib and Rituximab in people with IgM MGUS and Waldenstrom Macroglobulinemia, run by Shayna Sarosiek, MD at 2 sites 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 30 inclusion and 35 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: under way, not looking for participants, as of the sponsor's last update on 5 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
This study is still under way. Results are not available in the source record yet.
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?
Overall hematologic response rate (time frame: baseline to 6 years). 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 NCT05065554, which also lists 1 linked publication.
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 5 Dec 2025.