XEMBIFY® for Chronic Lymphocytic Leukemia

Recruiting at 98 trial locations

Overseen By Marina Acosta Enslen

Age: 18+

Sex: Any

Trial Phase: Phase 3

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) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

386 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether XEMBIFY® (an immune globulin therapy), administered every two weeks alongside standard medical care, can reduce serious bacterial infections in individuals with certain blood cancers, such as chronic lymphocytic leukemia (CLL), multiple myeloma (MM), or non-Hodgkin's lymphoma (NHL), who have low antibody levels (hypogammaglobulinemia). The trial compares this treatment to a placebo group receiving standard care. It seeks participants who have experienced at least one serious infection or multiple infections in the past year and have been diagnosed with one of these cancers. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Xembify is generally safe for people. In earlier studies, most side effects were mild or moderate. For example, headaches occurred in about 1 out of 49 people, while side effects affecting the whole body were reported in 7 out of 49 people. This indicates that while some side effects can occur, they are uncommon and usually not serious.

Additionally, the FDA has approved Xembify for treating primary humoral immunodeficiency, a condition where the immune system doesn't produce enough antibodies. This approval for another condition provides extra confidence about its safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Xembify® is unique because it offers a new approach for treating Chronic Lymphocytic Leukemia (CLL) by being administered subcutaneously, which is less invasive compared to the intravenous methods that are typical for CLL treatments like chemotherapy. Most current treatments for CLL involve drugs like ibrutinib or venetoclax, which target different pathways in cancer cells. However, Xembify® is an immunoglobulin therapy that can potentially enhance the immune system's ability to fight cancer cells. Researchers are excited about Xembify® because it might improve patient comfort and convenience with its biweekly infusion schedule, potentially reducing the frequency of hospital visits while still delivering effective treatment.

What evidence suggests that XEMBIFY® might be an effective treatment for chronic lymphocytic leukemia?

In this trial, participants will receive either Xembify or a placebo, both combined with Standard Medical Treatment (SMT). Studies have shown that Xembify, a type of immune globulin, effectively treats primary immunodeficiency by strengthening the immune system. This treatment raises antibody levels, which are proteins that fight infections, in the blood. This is crucial for patients with weakened immune systems, such as those with chronic lymphocytic leukemia (CLL). Research suggests that Xembify can be used alongside other CLL treatments, potentially improving overall results. One study found that Xembify kept immunoglobulin levels stable when administered every two weeks, which is promising for reducing infections. This makes Xembify a hopeful option for boosting the immune system in people with CLL and similar conditions. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Xembify

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.

How Is the Trial Designed?

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.

Xembify is already approved in United States for the following indications:

Approved in United States as Xembify for:

• Primary Humoral Immunodeficiency (PI) in patients 2 years of age and older

Who Is Running the Clinical Trial?

Grifols Therapeutics LLC

Lead Sponsor

Trials

59

Recruited

6,000+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. fda.gov fda.gov/media/182094/download

Clinical and Clinical Pharmacology Review STN: 125683/ ... Established Name Immune Globulin Subcutaneous, Human-klhw,. 20% (IGSC 20%). Trade Name XEMBIFY. Pharmacologic Class Biologic. Formulation(s) ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10117948/

An updated perspective on immunoglobulin replacement in ... This review aims to discuss the mechanisms by which CLL-targeted therapy may exert a synergistic therapeutic effect with immunoglobulin replacement therapy.

3. grifols.com grifols.com/en/view-news/-/news/grifols-achieves-positive-topline-results-from-phase-4-study-of-xembify-immune-globulin-subcutaneous-human-klhw-evaluating-biweekly-dosing-option-for-patients

Grifols achieves positive topline results from phase 4 study ... Clinical trial met primary endpoint demonstrating comparable total immunoglobulin (Ig) levels when administering XEMBIFY® (Grifols' ...

4. aetna.com aetna.com/products/rxnonmedicare/data/2025/SCIG_SGM_2043-A_P2024_R.html?ref=counterforcehealth.org

SCIG SGM 2043-A P2024_R Xembify (Immune Globulin Subcutaneous [Human} – klhw, 20% Solution). Xembify is indicated for treatment of primary humoral immunodeficiency (PI) in patients ...

5. aetnabetterhealth.com aetnabetterhealth.com/content/dam/aetna/medicaid/pdfs/formulary/guidelines/Subcutaneous-Immune-Globulins-Aetna-PENN-CHIP_FLHK_NJ_VA-Medicaid-Policy-ua.pdf

Coverage Policy/Guideline Xembify (Immune Globulin Subcutaneous [Human} – klhw, 20% Solution). Xembify is indicated for treatment of primary humoral immunodeficiency (PI) in patients ...

6. grifols.com grifols.com/en/view-news/-/news/grifols-receives-expanded-xembify-immune-globulin-subcutaneous-human-klhw-label-in-us-strengthening-its-ig-portfolio-for-patients

Grifols receives expanded XEMBIFY immune globulin ... XEMBIFY becomes the first 20% SCIg with this extended label, allowing patients to begin SCIg therapy without first having intravenous administration.

7. es.aetnabetterhealth.com es.aetnabetterhealth.com/content/dam/aetna/medicaid/pdfs/formulary/guidelines/Subcutaneous-Immune-Globulins-Aetna-PENN-CHIP_FLHK_NJ_IL_VA-Medicaid-Policy-ua.pdf

Subcutaneous Immune Globulins Xembify (Immune Globulin Subcutaneous [Human} – klhw, 20% Solution). Xembify is indicated for treatment of primary humoral immunodeficiency (PI) in patients ...

8. xembify.com xembify.com/en/hcp/tolerability

Safety & Tolerability All but one adverse event were mild or moderate*; Results per subject: overall rate of headaches (1/49); overall rate of systemic adverse reactions (7/49).