Trial Summary
What is the purpose of this trial?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
Do I have to stop taking my current medications to join the trial?The trial protocol does not specify if you must stop taking your current medications. However, you cannot take medications that are moderate or strong inhibitors or inducers of CYP3A within 7 days before the first dose of the study drug, and you cannot use a proton pump inhibitor daily. You may switch to H2-receptor antagonists or antacids instead.
Is the drug Acalabrutinib and Rituximab promising for treating peripheral neuropathy?Rituximab, one of the drugs in the treatment, has shown promise in treating peripheral neuropathy, especially in cases related to certain antibodies and conditions. It has been effective in reducing symptoms and improving the quality of life for patients with these types of neuropathy. This suggests that the combination with Acalabrutinib could be promising as well.23579
What safety data exists for Acalabrutinib and Rituximab in treating peripheral neuropathy?The safety data for Rituximab in treating neuropathy, particularly anti-MAG neuropathy, suggests it is generally well tolerated. Studies indicate that Rituximab can reduce B-cells and IgM levels, leading to clinical improvements in some patients. However, results are mixed, and larger controlled studies are needed to confirm its safety and efficacy. There is no specific safety data for Acalabrutinib in this context from the provided research.14789
What data supports the idea that Acalabrutinib + Rituximab for Peripheral Neuropathy is an effective drug?The available research shows that Rituximab, one of the drugs in the combination, has been effective in treating peripheral neuropathy associated with certain antibodies. For example, in one study, 62% of patients showed improvement in sensory and muscle strength scores after Rituximab treatment. Another study highlighted that Rituximab led to clinical improvement in patients with specific types of neuropathy. While there is no direct data on the combination of Acalabrutinib and Rituximab for peripheral neuropathy, Rituximab alone has shown promise in improving symptoms and reducing antibody levels in related conditions.23467
Eligibility Criteria
This trial is for people with IgM MGUS or Waldenström macroglobulinemia who have peripheral neuropathy. They must have good organ function, agree to use effective contraception, and be able to follow the study plan. Excluded are those with high serum IgM levels, prior chemotherapy/BTK inhibitors (except certain treatments over 90 days ago), other active cancers within 2 years (with some exceptions), uncontrolled diseases like heart failure or infections, and inability to take oral medication.Inclusion Criteria
I am using effective birth control or abstaining from sex.
I have been diagnosed with IgM MGUS or Waldenström macroglobulinemia.
Exclusion Criteria
I have not had major surgery in the last 4 weeks.
I do not have an active Hepatitis B or C infection.
My liver is severely impaired (Child-Pugh class C).
I am currently taking proton pump inhibitors every day.
I have nerve damage not caused by IgM-mediated neuropathy.
I do not have any severe illnesses or social situations that would stop me from following the study's requirements.
I plan to try for a child during or within 3 months after the study.
I have a current bleeding issue or a history of bleeding problems.
I do not have a serious infection currently.
I am on blood thinners like warfarin.
My heart condition severely limits my daily activities.
I have not received a live vaccine in the last 4 weeks.
I haven't taken drugs that strongly affect liver enzymes within the last week.
I have had symptoms of nerve damage for more than 5 years.
I cannot take medications by mouth due to a digestive condition.
I cannot swallow pills.
I have Waldenström macroglobulinemia and need treatment, but I don't have nerve pain in my hands or feet.
I do not have MZL, CLL, MCL, IgM Myeloma, or AL amyloidosis.
I do not have uncontrolled AIHA or ITP.
I have been diagnosed with lymphoma in my brain or spinal cord.
Treatment Details
The trial tests a combination of acalabrutinib (a new treatment) and rituximab (or similar CD20 antibody) against neuropathies related to IgM MGUS or Waldenström macroglobulinemia. It aims to find out if this drug duo is safe and more effective compared to current standard therapies.
1Treatment groups
Experimental Treatment
Group I: ACALABRUTINIB + RITUXIMAB/BIOSIMILARExperimental Treatment2 Interventions
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
Acalabrutinib is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Calquence for:
- Mantle cell lymphoma
- Chronic lymphocytic leukemia
- Small lymphocytic lymphoma
🇪🇺 Approved in European Union as Calquence for:
- Chronic lymphocytic leukemia
- Small lymphocytic lymphoma
- Mantle cell lymphoma
Find a clinic near you
Research locations nearbySelect from list below to view details:
Massachusetts General HospitalBoston, MA
Dana Farber Cancer InstituteBoston, MA
Loading ...
Who is running the clinical trial?
Shayna Sarosiek, MDLead Sponsor
Jorge J. Castillo, MDLead Sponsor
AstraZenecaIndustry Sponsor
References
Rituximab in the treatment of polyneuropathy associated with anti-MAG antibodies. [2015]No causative or curative therapy exists for the polyneuropathy associated with antibodies to myelin-associated glycoprotein (anti-MAG). Rituximab is a mouse-human chimeric antibody that specifically eliminates B-cells and B-cell precursors. Preliminary results suggest a beneficial effect on antibody-dependent autoimmune diseases. Nine patients with an anti-MAG-associated IgM polyneuropathy received rituximab once weekly for 4 weeks. In all patients, the number of B-cells in the peripheral blood declined below levels of detection, and the IgM levels decreased between 35% and 82% (median, 58%). In eight patients, lowering of the anti-MAG antibody titers of more than 52% was observed. Clinical status improved in six patients, remained stable in two, and worsened in one. The motor nerve conduction velocity improved by at least 10% in one ulnar nerve in seven patients and worsened in two. Rituximab was well tolerated and is a promising new drug in the treatment of patients with anti-MAG-associated polyneuropathy.
Rituximab treatment of an IgM monoclonal autonomic and sensory neuropathy. [2015]Rituximab, a monoclonal antibody against B-cell membrane marker CD-20, is an effective treatment for immunoglobulin M (IgM) monoclonal anti-myelin-associated glycoprotein (MAG) neuropathies. We report a patient with an autonomic and painful sensory neuropathy associated with an IgM lambda monoclonal gammopathy, responsive to rituximab. Treatment resulted in a decline in total IgM and improvement in the patient's painful neuropathy and dysautonomia. Rituximab may be an effective and tolerable treatment for autonomic and sensory neuropathy associated with IgM monoclonal gammopathy.
Rituximab in the treatment of peripheral neuropathy associated with monoclonal gammopathy. [2015]Peripheral neuropathy associated with immunoglobulin (Ig)M gammopathy and anti-myelin-associated glycoprotein antibodies is frequently treatment-resistant and different treatment regimens carry substantial toxicity and side effects. More recently, the chimeric anti-CD20 monoclonal antibody rituximab has shown benefits in the treatment of peripheral neuropathy associated with IgM gammopathy with a favorable side-effect profile. There are no published reports of its use in the treatment of neuropathy associated with IgG and IgA gammopathies. Rituximab is usually given at 375 mg/m(2) intravenously with four weekly doses that may be repeated after 6-12 months. Large controlled studies are still pending but rituximab is an exciting and promising treatment offering another option in the treatment of peripheral neuropathy associated with IgM monoclonal gammopathy.
Predictors of response to rituximab in patients with neuropathy and anti-myelin associated glycoprotein immunoglobulin M. [2015]We evaluated the efficacy and safety of rituximab in an open-label, uncontrolled study of 13 patients with polyneuropathy associated with antibodies to myelin-associated glycoprotein (MAG) and correlated the response to therapy with clinical and laboratory features. One year after rituximab therapy, anti-MAG immunoglobulin M (IgM) titers were significantly reduced. At that time, eight patients (62%) had improved in both the inflammatory neuropathy cause and treatment (INCAT) sensory sumscore and the Medical Research Council sumscore for muscle strength and seven of them also in the INCAT disability score. The improvement in the mean INCAT sensory sumscore was significant at 12 months and correlated with lower anti-MAG antibody at entry and at follow-up. This study suggests that rituximab may be efficacious in patients with anti-MAG associated neuropathy and particularly on sensory impairment and in those with moderately elevated antibody titers. These findings suggest that antibody reduction below a critical level may be necessary to achieve clinical improvement.
Rituximab in cryoglobulinemic peripheral neuropathy. [2021]Type II mixed cryoglobulinemia is sustained by an oligoclonal production of IgM sharing rheumatoid activity and can be associated with renal, cutaneous, rheumatologic or neurological manifestations. Peripheral neuropathy is a major cause of morbidity in hepatitis C virus-associated mixed cryoglobulinemia and is often refractory to any treatment. Rituximab induces a selective depletion of IgM-producing B cells, and both case reports on monoclonal IgM-related polyneuropathy as well as studies on small series of patients with interferon alpha-resistant mixed cryoglobulinemia have suggested that it may be beneficial. Thirteen patients affected by type II mixed cryoglobulinemia with polyneuropathy were treated. Rituximab was administered intravenously at a dose of 375 mg/m(2) on days 1, 8, 15 and 22. Two more doses were given 1 and 2 months later. No other immunosuppressive drugs were added. Response was evaluated by assessing the changes in the clinical neurological condition, in electromyographic indices and in laboratory parameters (including cryocrit, viral load, complement levels and rheumatoid factor) over at least 12 months. Sensory symptoms disappeared or improved following treatment. A significant improvement in the clinical neuropathy disability score was observed. Electromyography examination revealed that the amplitude of compound motor action potential had increased. Viral load did not significantly change. Side effects were negligible. In this open prospective study, rituximab appeared to be effective and safe in the treatment of patients with type II cryoglobulinemia-associated neuropathy.
Neurophysiological and clinical responses to rituximab in patients with anti-MAG polyneuropathy. [2015]Rituximab treatment has shown clinical improvement in anti-myelin associated glycoprotein (MAG) polyneuropathy. We analyzed scores of clinical scales and the most sensitive electrophysiological parameters before and after immunomodulating treatment with rituximab in a group of patients affected by anti-MAG demyelinating polyneuropathy.
Placebo-controlled trial of rituximab in IgM anti-myelin-associated glycoprotein neuropathy. [2021]To determine whether rituximab 375 mg/m(2) was efficacious in patients with immunoglobulin M (IgM) anti-myelin-associated glycoprotein antibody demyelinating neuropathy (IgM anti-MAG demyelinating neuropathy).
Beneficial effects of Rituximab in patients with anti-MAG (myelin-associated glycoprotein) neuropathy: case reports. [2015]Anti-myelin-associated glycoprotein (MAG) neuropathy is a primary demyelinating sensorimotor polyneuropathy that can be very debilitating and is known to be resistant to treatment. There are only a few conflicting reports on the effect of Rituximab in anti-MAG neuropathy. We present three patients who improved remarkably with Rituximab infusions. Until the safety and efficacy of this drug are determined in larger controlled studies, use of Rituximab should be limited to patients with significant neurologic deficits.
Obinutuzumab, a new anti-CD20 antibody, and chlorambucil are active and effective in anti-myelin-associated glycoprotein antibody polyneuropathy. [2019]Rituximab, a chimeric anti-CD20 monoclonal antibody, has been used in polyneuropathy associated with anti-myelin-associated glycoprotein (anti-MAG) antibody polyneuropathy with controversial results. Herein, two patients with anti-MAG antibody neuropathy and concurrent chronic lymphocytic leukemia (CLL) are reported, who dramatically responded to obinutuzumab, a novel glycoengineered humanized anti-CD20 monoclonal antibody.