XEMBIFY® for Chronic Lymphocytic Leukemia

Recruiting in Palo Alto (17 mi)

+67 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Grifols Therapeutics LLC

Must not be taking: Immunoglobulin, Anticoagulants

Disqualifiers: Stem cell transplant, Active infections, Second malignancies, Primary immunodeficiency, others

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial is testing if adding XEMBIFY® to usual care can reduce serious bacterial infections in patients with low antibody levels due to a type of leukemia. XEMBIFY® helps by giving extra antibodies to boost the immune system. The goal is to see if this combination works better than usual care alone. XEMBIFY® is used to prevent bacterial infections in patients with chronic lymphocytic leukemia.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, certain supportive treatments for infections are allowed, and some medications might be recommended based on guidelines for your condition.

What data supports the effectiveness of the drug XEMBIFY® for treating chronic lymphocytic leukemia?

Research suggests that subcutaneous immunoglobulin (SCIG) replacement therapy, like XEMBIFY®, is effective and safe in preventing infections in patients with chronic lymphocytic leukemia who have low levels of antibodies (hypogammaglobulinemia). This makes it a valuable option for managing infection risks in these patients. ^{1 2 3 4 5}

How is the drug Xembify unique for treating chronic lymphocytic leukemia?

Xembify is unique because it is a high concentration immunoglobulin product administered subcutaneously (under the skin), which allows for a smaller volume and potentially better tolerability compared to intravenous options. It is used to address hypogammaglobulinemia (low levels of antibodies) in CLL patients, helping to reduce the risk of infections. ^{3 5 6 7 8}

Research Team

Eligibility Criteria

Adults over 18 with B-cell chronic lymphocytic leukemia and low immunoglobulin G levels who've had severe or repeated bacterial infections. Not for those with short life expectancy, certain diseases, on anticoagulants, high blood pressure, recent other trials, kidney disease, current infection treatments (except specific prophylactics), prior immunoglobulin therapy within 6 months, liver issues, skin disorders contraindicating subcutaneous therapy, drug abuse history within a year, active second cancers or known primary immunodeficiency.

Inclusion Criteria

My cancer is classified as intermediate or high risk.

My IgG levels are below 4 g/L.

My diagnosis is B-cell CLL, confirmed by international standards.

Exclusion Criteria

My liver enzyme levels are more than three times the normal limit.

I have been diagnosed with Selective IgA Deficiency.

I do not have any major health issues that could affect my participation in the trial.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive XEMBIFY® or placebo plus Standard Medical Treatment. Initial loading dose for 5 consecutive days followed by biweekly infusions for one year.

52 weeks

Biweekly visits for infusions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo (Other)
• Xembify (Monoclonal Antibodies)

Trial Overview The trial tests if XEMBIFY® plus Standard Medical Treatment reduces major bacterial infections in patients with hypogammaglobulinemia from B-cell CLL compared to a placebo group. It's administered weekly for one year to see the difference in infection rates between the two groups.

Participant Groups

Group I: XEMBIFY + Standard Medical Treatment (SMT) Experimental Treatment 1 Intervention

Participants will receive a loading dose of 150 milligrams per kilograms per day (mg/kg/day) (Week 1, Days 1 to 5) subcutaneously (SC) for 5 consecutive daily doses followed by biweekly infusions of 300 mg/kg/2-week starting Week 3 (Day 15) through Week 51 (end of Treatment Phase). The SMT will include the active treatments and the other supportive treatments that the participants will need during their participation.

Group II: Placebo + SMT Placebo Group 1 Intervention

Participants will receive sterile 0.9 percent Sodium Chloride Injection (commercially available in the corresponding country) starting at Week 1 (Days 1 to 5) SC for 5 consecutive daily doses followed by biweekly infusions starting at Week 3 (Day 15) through Week 51. The SMT will include the active treatments and the other supportive treatments that the participants will need during their participation.

Who Is Running the Clinical Trial?

Grifols Therapeutics LLC

Lead Sponsor

Trials

59

Recruited

6,000+

Findings from Research

Subcutaneous alemtuzumab is effective in treating residual disease in chronic lymphocytic leukemia (CLL), with 23 out of 29 evaluable patients responding positively to the treatment after self-administration.

Higher plasma levels of alemtuzumab at the end of treatment were associated with longer response durations, highlighting the importance of monitoring drug levels and minimal residual disease in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Self-administered, subcutaneous alemtuzumab to treat residual disease in patients with chronic lymphocytic leukemia. Wierda, WG., Kipps, TJ., Keating, MJ., et al.[2021]

A phase 2 clinical trial evaluated the effectiveness of rituximab maintenance therapy in patients with chronic lymphocytic leukemia (CLL) who had previously received a combination treatment of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM).

The study aimed to assess the outcomes of continuing rituximab therapy after initial treatment, which could provide insights into improving long-term management of CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance in CLL. Robak, T.[2021]

In a study of 15 patients with chronic lymphocytic leukemia (CLL) who had serum IgG levels above 400 mg/dL, 93.3% showed humoral immunodeficiency, indicating that high IgG levels do not guarantee adequate immune function.

Treatment with subcutaneous immunoglobulin (SCIG) significantly increased serum IgG levels and specific immunity to Streptococcus pneumoniae, while also reducing non-neutropenic infections from 14 to 5 during the 24-week treatment period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous immunoglobulin replacement for treatment of humoral immune dysfunction in patients with chronic lymphocytic leukemia. Mustafa, SS., Jamshed, S., Vadamalai, K., et al.[2021]

Chronic lymphocytic leukaemia (CLL) primarily affects older adults, particularly men, and asymptomatic patients can expect a life expectancy similar to the general population, often requiring only monitoring.

Chlorambucil is the standard treatment for symptomatic CLL, while fludarabine is used if chlorambucil is ineffective; however, combination therapies do not show improved outcomes compared to these single-agent treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic lymphocytic leukaemia: only treat when symptomatic. [2013]

Intravenous and subcutaneous immunoglobulin replacement therapy (IgRT) is effective and safe for preventing infections in patients with chronic lymphocytic leukemia (CLL) and hypogammaglobulinemia, making it an important management tool.

Subcutaneous immunoglobulin (SCIg) formulations are recommended over intravenous immunoglobulin (IVIg) due to their similar efficacy, better cost-effectiveness, and improved tolerability for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Should treatment of hypogammaglobulinemia with immunoglobulin replacement therapy (IgRT) become standard of care in patients with chronic lymphocytic leukemia? Noto, A., Cassin, R., Mattiello, V., et al.[2023]

The new IGSC-C 20% formulation of immune globulin is designed for subcutaneous administration, providing a higher protein concentration (20%) compared to the previous 10% formulation, which allows for smaller injection volumes.

IGSC-C 20% maintains the same quality, purity, and neutralizing activity as the 10% version, ensuring its safety and efficacy for patients requiring immunoglobulin therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune globulin subcutaneous, human 20% solution (Xembify®), a new high concentration immunoglobulin product for subcutaneous administration. Alonso, W., Vandeberg, P., Lang, J., et al.[2020]

In a study involving 228 previously untreated CLL patients, high dose chlorambucil (HD-CLB) demonstrated a significantly higher overall response rate of 89.5% compared to 75% for the CHOP regimen, indicating its superior efficacy in treating advanced CLL.

Patients receiving HD-CLB also experienced longer median survival (68 months) compared to those on CHOP (47 months), with both treatments showing comparable and acceptable toxicity levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High dose chlorambucil versus Binet's modified cyclophosphamide, doxorubicin, vincristine, and prednisone regimen in the treatment of patients with advanced B-cell chronic lymphocytic leukemia. Results of an international multicenter randomized trial. International Society for Chemo-Immunotherapy, Vienna. Jaksic, B., Brugiatelli, M., Krc, I., et al.[2015]

Chlorambucil, an oral chemotherapy drug, was administered to eight patients with various hematological malignancies, resulting in partial remission in several cases, particularly in chronic lymphocytic leukemia (CLL) and certain types of lymphoma.

The treatment was generally well-tolerated, allowing for longer use without severe toxicity, although some patients experienced myelosuppression, particularly leukopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phase II study of chlorambucil in patients with hematological malignancies]. Inoue, K., Ogawa, M., Horikoshi, N., et al.[2013]

References

1. United States pubmed.ncbi.nlm.nih.gov

Self-administered, subcutaneous alemtuzumab to treat residual disease in patients with chronic lymphocytic leukemia. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Maintenance in CLL. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Subcutaneous immunoglobulin replacement for treatment of humoral immune dysfunction in patients with chronic lymphocytic leukemia. [2021]

4. France pubmed.ncbi.nlm.nih.gov

Chronic lymphocytic leukaemia: only treat when symptomatic. [2013]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Should treatment of hypogammaglobulinemia with immunoglobulin replacement therapy (IgRT) become standard of care in patients with chronic lymphocytic leukemia? [2023]

6. England pubmed.ncbi.nlm.nih.gov

Immune globulin subcutaneous, human 20% solution (Xembify®), a new high concentration immunoglobulin product for subcutaneous administration. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

High dose chlorambucil versus Binet's modified cyclophosphamide, doxorubicin, vincristine, and prednisone regimen in the treatment of patients with advanced B-cell chronic lymphocytic leukemia. Results of an international multicenter randomized trial. International Society for Chemo-Immunotherapy, Vienna. [2015]

8. Japan pubmed.ncbi.nlm.nih.gov

[Phase II study of chlorambucil in patients with hematological malignancies]. [2013]