Daratumumab for Lymphoma

Overseen By Kathryn A Lurain, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Antiretrovirals

Disqualifiers: Kaposi sarcoma, Cardiac disease, COPD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Up to 24 months

28 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: Primary effusion lymphoma (PEL) is an aggressive form of cancer that affects cells in the immune system and lymph nodes. How PEL develops is not well understood, and this disease does not respond well to standard treatments for other types of lymphomas. Objective: To test a drug treatment (daratumumab SC) in people with PEL. Eligibility: People aged 18 and older with PEL. Their PEL must have failed to respond to therapy or they must be unable to receive standard treatment for the disease. Design: Participants will be screened. They will have a physical exam with blood tests. They will have imaging scans and tests of their heart and lung function. They may need to have a biopsy: tissue or fluid will be collected. They will have an eye exam. Daratumumab SC is given as an injection into the fat under the skin in the abdomen. This takes 3 to 5 minutes. Participants will receive the treatment once a week for 8 weeks; then every 2 weeks for 16 weeks; then every 4 weeks for up to 24 months. Participants will have other tests during the study period. These may include lumbar punctures: A needle will be inserted between the bones of the spine to draw some fluid from the area around the spinal cord. Participants may also have a thoracentesis: A needle or plastic tube will be inserted into the space around the lungs to withdraw fluid. Participants will have more imaging scans and blood tests. Follow-up visits will continue after treatment ends. Participants will be in the study for up to 5 years.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have been on investigational agents from other clinical trials, a washout period (time without taking certain medications) of 2 weeks or 5 drug half-lives is required, whichever is longer.

What safety data exists for Daratumumab in humans?

In the APOLLO trial, Daratumumab was studied in combination with other drugs for multiple myeloma, and safety results were updated, indicating it has been evaluated for safety in humans. ^{1 2 3 4 5}

How does the drug Daratumumab SC differ from other treatments for lymphoma?

Daratumumab SC is unique because it is administered subcutaneously (under the skin), which can be more convenient and faster than intravenous (into the vein) treatments like Rituximab, commonly used for lymphoma. Additionally, Daratumumab targets a different protein, CD38, compared to Rituximab, which targets CD20, offering a novel mechanism of action for treating lymphoma. ^{6 7 8 9 10}

Research Team

Kathryn A Lurain, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults with Primary Effusion Lymphoma (PEL) that's resistant to standard treatment or those who can't receive it. Eligible participants include any HIV status, but if positive, they must have a certain CD4 count and be on effective antiretroviral therapy. They should have adequate blood and kidney function, not be pregnant, agree to contraception use during the study, and sign consent.

Inclusion Criteria

My lymphoma has returned or didn't respond to initial treatment, and it's confirmed by NCI.

Women of child-bearing potential (WOBP) must agree to use an effective (dual) form of contraception (barrier, surgical sterilization, abstinence) prior to study entry and for the duration of study participation and for 3 months after the last dose of study drug. Men must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) for the duration of the study treatment and up to 3 months after the last dose of the study drug(s). Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 3 months after the last dose of the study drug. Participants must understand and sign a written informed consent document.

My HIV status is any, and if positive, my CD4 count meets the required levels.

Exclusion Criteria

I haven't had cancer treatment in the last 2 weeks, or it was for a cancer that won't affect this trial. Any side effects from past treatments are mild.

I am not pregnant and do not have a severe uncontrolled illness.

I do not have serious heart issues, severe asthma, or very poor lung function.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Daratumumab SC is administered weekly for 8 weeks, then every 2 weeks for 16 weeks, and then every 4 weeks for up to 24 months

Up to 24 months

Weekly visits initially, then bi-weekly, then monthly

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Regular follow-up visits

Treatment Details

Interventions

• Daratumumab SC

Trial Overview The trial is testing Daratumumab SC as an injection for PEL patients. It involves initial weekly treatments for 8 weeks, then every two weeks for 16 weeks followed by monthly doses up to two years. Participants will undergo various tests including biopsies, scans, lumbar punctures and thoracentesis over a period of up to five years.

Participant Groups

Group I: Arm 1 Experimental Treatment 1 Intervention

Treatment with daratumumab SC

Daratumumab SC is already approved in European Union, United States for the following indications:

Approved in European Union as Darzalex for:

• Relapsed and refractory multiple myeloma
• Newly diagnosed multiple myeloma

Approved in United States as Darzalex for:

• Multiple myeloma
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In the APOLLO trial involving 304 patients with relapsed or refractory multiple myeloma, the combination of daratumumab, pomalidomide, and dexamethasone showed a median overall survival of 34.4 months compared to 23.7 months for pomalidomide and dexamethasone alone, although this difference was not statistically significant.

The safety profile indicated that serious treatment-emergent adverse events were more common in the daratumumab group (54%) compared to the pomalidomide and dexamethasone group (40%), but the overall findings support the continued use of daratumumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma (APOLLO): extended follow up of an open-label, randomised, multicentre, phase 3 trial. Dimopoulos, MA., Terpos, E., Boccadoro, M., et al.[2023]

Abiraterone and enzalutamide significantly improve survival outcomes in patients with castration-resistant prostate cancer (CRPC), with pooled hazard ratios indicating a 28% reduction in overall mortality and a 55% reduction in radiographic progression-free survival based on a review of 8 randomized controlled trials involving 6,490 patients.

While these treatments are effective, they are associated with a higher incidence of adverse events, including fatigue, hypertension, and fluid retention, suggesting that while the benefits are substantial, patients should be monitored for these potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of abiraterone and enzalutamide for castration-resistant prostate cancer: A systematic review and meta-analysis of randomized controlled trials. Zheng, X., Zhao, X., Xu, H., et al.[2021]

Gleevec (imatinib mesylate) has been approved for treating malignant gastrointestinal stromal tumors, showing efficacy at doses of 400 or 600 mg daily, indicating its role in managing aggressive cancer types.

Zometa (zoledronic acid) is approved for patients with multiple myeloma and bone metastases, demonstrating its effectiveness as a supportive care drug when used alongside standard cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration drug approval summaries: imatinib mesylate, mesna tablets, and zoledronic acid. Cohen, MH., Dagher, R., Griebel, DJ., et al.[2019]

Darolutamide is a novel androgen receptor antagonist that has shown a high affinity for androgen receptors and maintains its effectiveness even against mutant forms, making it a promising option for treating nonmetastatic castration-resistant prostate cancer (nmCRPC).

Compared to other similar drugs like apalutamide and enzalutamide, darolutamide has a lower likelihood of causing adverse events, suggesting a better safety profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An up-to-date evaluation of darolutamide for the treatment of prostate cancer. Moussa, M., Lazarou, L., Dellis, A., et al.[2021]

In a study of 31 prostate cancer patients with underlying inflammatory bowel disease (IBD) treated with stereotactic body radiation therapy (SBRT), no biochemical relapses were observed, indicating effective cancer treatment.

The use of modern radiation techniques resulted in rare high-grade toxicities, with only one case of grade 3 proctitis, suggesting that contemporary methods can safely mitigate the risk of gastrointestinal side effects in IBD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy for the treatment of localized prostate cancer in men with underlying inflammatory bowel disease. Lischalk, JW., Blacksburg, S., Mendez, C., et al.[2022]

Rituximab (RTX) is a widely used monoclonal antibody for treating diffuse large B-cell lymphoma, often combined with other drugs in the R-CHOP regimen, but some patients experience suboptimal responses or resistance.

New developments in CD20-targeting monoclonal antibodies, including second- and third-generation agents like ofatumumab and obinutumumab, are being actively researched to improve treatment outcomes for B-cell non-Hodgkin's lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel CD20 monoclonal antibodies for lymphoma therapy. Cang, S., Mukhi, N., Wang, K., et al.[2022]

In a phase II study involving 54 patients with aggressive B-cell lymphomas, rituximab demonstrated significant clinical activity, achieving an overall response rate of 31%, with complete responses in 9% and partial responses in 22% of patients.

The treatment was well-tolerated, with mild adverse events primarily related to infusion syndrome, indicating that rituximab could be a safe option for patients with diffuse large B-cell lymphoma (DLCL) and mantle cell lymphoma (MCL).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: a multicenter phase II study. Coiffier, B., Haioun, C., Ketterer, N., et al.[2022]

Rituximab is an effective anti-CD20 monoclonal antibody that has demonstrated single-agent activity in treating B-cell non-Hodgkin's lymphoma, with a long serum half-life and low immunogenicity, making it a promising therapy.

While initial infusions can cause mild infusion symptoms and temporary B-cell depletion, these effects are generally manageable and not linked to immunodeficiency, supporting its use alongside or after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical and phase I and II trials of rituximab. Maloney, DG.[2015]

Rituximab, an anti-CD20 monoclonal antibody, has been approved for treating relapsed or refractory low-grade and follicular B-cell non-Hodgkin's lymphoma, achieving a 50% overall response rate with a median progression-free survival of 13.2 months.

A Phase I/II study of the 90Y-labelled anti-CD20 antibody, IDEC-Y2B8, showed a higher response rate of 67% in patients with low-grade and intermediate-grade non-Hodgkin's lymphoma, indicating promising efficacy for this treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD20 monoclonal antibodies as novel treatments for non-Hodgkin's lymphoma. White, CA., Larocca, A., Grillo-López, AJ.[2020]

Rituximab, a chimeric anti-CD20 monoclonal antibody, is a standard treatment for non-Hodgkin's lymphoma (NHL) and has been used in over 300,000 patients worldwide, demonstrating its widespread acceptance and efficacy.

The combination of rituximab with standard CHOP chemotherapy is approved for treating diffuse large B-cell lymphoma, and while it is generally well tolerated, common side effects include infusion-related reactions like chills and fever.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An overview of the current clinical use of the anti-CD20 monoclonal antibody rituximab. Boye, J., Elter, T., Engert, A.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Subcutaneous daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma (APOLLO): extended follow up of an open-label, randomised, multicentre, phase 3 trial. [2023]

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

Efficacy and safety of abiraterone and enzalutamide for castration-resistant prostate cancer: A systematic review and meta-analysis of randomized controlled trials. [2021]

3. England pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration drug approval summaries: imatinib mesylate, mesna tablets, and zoledronic acid. [2019]

4. England pubmed.ncbi.nlm.nih.gov

An up-to-date evaluation of darolutamide for the treatment of prostate cancer. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy for the treatment of localized prostate cancer in men with underlying inflammatory bowel disease. [2022]

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

Novel CD20 monoclonal antibodies for lymphoma therapy. [2022]

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

Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: a multicenter phase II study. [2022]

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

Preclinical and phase I and II trials of rituximab. [2015]

9. England pubmed.ncbi.nlm.nih.gov

Anti-CD20 monoclonal antibodies as novel treatments for non-Hodgkin's lymphoma. [2020]

10. England pubmed.ncbi.nlm.nih.gov

An overview of the current clinical use of the anti-CD20 monoclonal antibody rituximab. [2020]