Daratumumab + Chemotherapy for Lymphoma

Recruiting at 7 trial locations

Overseen By Ariela Noy, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: AIDS Malignancy Consortium

Must be taking: HAART

Must not be taking: CYP3A4 inhibitors

Disqualifiers: Brain metastases, Hepatitis B, others

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

Compensation: Varies

Number of Visits: 4

Duration: 18 weeks

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination to combat plasmablastic lymphoma, a rare cancer. The focus is on pairing daratumumab, which targets a protein on cancer cells, with a mix of chemotherapy drugs, including cyclophosphamide, doxorubicin, etoposide, and prednisone. The goal is to determine if this combination can more effectively halt the growth and spread of cancer cells. Individuals recently diagnosed with stage I-IV plasmablastic lymphoma and aware of their HIV status might be suitable candidates. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you cannot be on certain drugs like cobicistat, indinavir, ritonavir, or strong CYP3A4 inhibitors. If you are taking these, you must switch to other medications at least one week before starting the trial.

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

A previous study observed common side effects when daratumumab was combined with other treatments. These included low white blood cell levels in about 44% of patients, low levels of a specific type of white blood cell in 31% of patients, and low platelet counts in 25% of patients. These side effects are called treatment-emergent adverse events because they occurred after treatment began.

The FDA has already approved daratumumab for treating multiple myeloma, a different type of cancer. This approval indicates that it has been well-studied and is generally considered safe for that use. However, this trial is in the early stages of testing daratumumab for plasmablastic lymphoma, so complete safety information for this specific use is not yet available. Still, its use in other conditions provides some confidence about its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for lymphoma, which typically involve chemotherapy alone, this new approach combines daratumumab, a monoclonal antibody, with chemotherapy. Daratumumab is unique because it specifically targets the CD38 protein found on the surface of lymphoma cells, potentially enhancing the immune system's ability to attack the cancer. This targeted action is different from traditional chemotherapy, which affects both cancerous and healthy cells. Researchers are excited about this treatment because it might offer a more precise attack on lymphoma cells, possibly leading to better outcomes with fewer side effects.

What evidence suggests that daratumumab combined with DA-EPOCH could be an effective treatment for plasmablastic lymphoma?

In this trial, participants will receive a combination of daratumumab with the chemotherapy regimen DA-EPOCH. Research has shown that daratumumab, when combined with chemotherapy, may effectively treat plasmablastic lymphoma. This type of lymphoma exhibits high levels of a protein called CD38, which daratumumab targets. By focusing on CD38, daratumumab may enhance the immune system's ability to attack cancer cells. Previous studies have demonstrated that adding daratumumab to chemotherapy, such as DA-EPOCH, can lead to complete remission in some patients. The chemotherapy drugs in this combination work by stopping cancer cells from growing, dividing, or spreading. Early reports suggest that daratumumab enhances the effectiveness of chemotherapy in combating this aggressive cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Ariela Noy, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed stage I-IV plasmablastic lymphoma. Participants can be HIV-positive or negative but must meet specific criteria, including certain blood cell counts and organ function levels. They should not have had previous chemotherapy for lymphoma, except under certain conditions, and cannot have severe lung disease, active hepatitis B or C infections, brain metastases from solid tumors, or a history of allergic reactions to the study drugs.

Inclusion Criteria

My cancer is at an advanced stage or early stage with high LDH/bulky tumor.

You will need to take an HIV test that is confirmed by a second test to make sure you do not have HIV.

Measurable disease or evaluable by bone marrow

Exclusion Criteria

I have not had anthracycline treatment in the last 2 years, except for liposomal doxorubicin.

I have severe nerve damage or pain.

I do not have brain or spinal cord disease related to lymphoma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daratumumab and DA-EPOCH chemotherapy for up to 6 cycles

18 weeks

Visits on days 1, 8, and 15 of cycles 1-3; day 1 of cycles 4-6

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Daratumumab
• Doxorubicin
• Etoposide
• Prednisone

Trial Overview The trial tests daratumumab combined with DA-EPOCH chemotherapy (etoposide, prednisone, vincristine sulfate, cyclophosphamide, doxorubicin hydrochloride) in treating plasmablastic lymphoma. Daratumumab targets CD38 protein on cancer cells to help the immune system attack the cancer while chemotherapy aims to stop cancer growth by killing cells or preventing their division.

How Is the Trial Designed?

Group I: Treatment (daratumumab, DA-EPOCH) Experimental Treatment 8 Interventions

Patients receive daratumumab IV on days 1 (± 3 days), 8 (± 2 days), and 15 (± 2 days), of cycles 1-3, and on day 1 of cycles 4-6. Patients also receive etoposide, doxorubicin hydrochloride, and vincristine sulfate IV continuous over 96 hours on days 1-4, prednisone PO on days 1-5, and cyclophosphamide IV over 1 hour on day 5. Treatment repeats every 21 days for up to 6 cycles in absence of disease progression or unacceptable toxicity.

Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

AIDS Malignancy Consortium

Lead Sponsor

Trials

64

Recruited

9,600+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Joaquin Duato

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Montefiore Medical Center

Collaborator

Trials

468

Recruited

599,000+

Memorial Sloan Kettering Cancer Center

Collaborator

Trials

1,998

Recruited

602,000+

AIDS and Cancer Specimen Resource

Collaborator

Trials

8

Recruited

990+

The Emmes Company, LLC

Industry Sponsor

Trials

149

Recruited

1,052,000+

Peter Ronco

The Emmes Company, LLC

Chief Executive Officer since 2023

BSc from Nottingham University

Dr. Joe Sliman

The Emmes Company, LLC

Chief Medical Officer since 2020

MD from Uniformed Services University of the Health Sciences, MPH from Johns Hopkins University, BSc in Molecular and Cell Biology from Pennsylvania State University

Published Research Related to This Trial

In a study of 35 elderly patients with aggressive non-Hodgkin's lymphoma, the use of liposomal Daunorubicin (DNX) resulted in a high overall response rate of 77%, with 15 patients achieving complete remission (CR) and 5 achieving partial remission (PR).

Liposomal DNX demonstrated similar efficacy to traditional Daunorubicin while significantly reducing acute toxicity, making it a safer option for treating this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and toxicity of liposomal daunorubicin included in PVABEC regimen for aggressive NHL of the elderly. Cervetti, G., Caracciolo, F., Cecconi, N., et al.[2019]

In a study of 195 patients with relapsed/refractory aggressive B-cell lymphomas, the overall response rate to second-line platinum-based immunochemotherapy was 44%, with a median progression-free survival (PFS) of 3 months and overall survival (OS) of 8 months.

Patients who experienced early treatment failure (relapse within 12 months of first-line therapy) had significantly worse outcomes, with a median PFS of only 2.8 months and OS of 6 months, suggesting a need for alternative treatment strategies in this high-risk group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes in patients with aggressive B-cell non-Hodgkin lymphoma after intensive frontline treatment failure. Ayers, EC., Li, S., Medeiros, LJ., et al.[2020]

The R-CHOP regimen, which includes rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, is a standard first-line treatment for diffuse large B-cell lymphoma, highlighting its importance in oncology.

Nursing implications of administering R-CHOP are significant, as the combination of these drugs requires careful monitoring for side effects and patient management during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nursing Alchemy: Transforming R-CHOP Information Into Essentials. Sakowski, AK., Patel, PR.[2023]

In a study of 20 patients with untreated poor prognosis diffuse large B-cell lymphoma (DLBCL), the two-weekly dose-adjusted EPOCH-like chemotherapy (DA-EDOCH14-R) showed a promising three-year progression-free survival (PFS) rate of 95%, compared to 74% in a previous trial with a three-weekly regimen.

The treatment was well-tolerated with manageable toxicity and no therapy-related deaths, highlighting its safety, especially for patients with a high-risk prognosis (age-adjusted International Prognostic Index of 3), where PFS reached 100% compared to just 30% in the previous trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-weekly dose-adjusted (DA)-EPOCH-like chemotherapy with high-dose dexamethasone plus rituximab (DA-EDOCH14-R) in poor-prognostic untreated diffuse large B-cell lymphoma. García-Suárez, J., Flores, E., Callejas, M., et al.[2015]

In a study of 81 patients with advanced diffuse large cell lymphoma, the epipodophyllotoxin VP-16-213 alone achieved a complete remission rate of 55%, while its combination with doxorubicin also showed a high remission rate of 62%, indicating that VP-16-213 is an effective treatment option.

The combination of VP-16-213 with cyclophosphamide was found to be inferior, with a complete remission rate of only 29%, suggesting that this combination may not be beneficial for patients with this type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

VP-16-213 in the treatment of stage III and IV diffuse large cell lymphoma. Jacobs, P., King, HS., Dent, DM., et al.[2019]

In a study of 115 patients with Waldeyer's ring diffuse large B-cell lymphoma, those treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab (DA-EPOCH-R) showed significantly better progression-free survival (PFS) and overall survival (OS) compared to those receiving standard R-CHOP treatment, with 2-year PFS rates of 90.1% versus 80.5%.

The DA-EPOCH-R treatment was associated with fewer deaths (2 out of 42 patients) compared to R-CHOP (9 out of 42 patients) during a median follow-up of 45 months, while both treatments had similar clinical responses and treatment-related toxicities, indicating that DA-EPOCH-R is a safer and more effective option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-adjusted EPOCH-R vs. R-CHOP in frontline management of Waldeyer's ring diffuse large B-cell lymphoma: a retrospective study from a single institution. Liang, Y., Liu, X., Yang, J., et al.[2023]

Etoposide is a key drug in treating malignant lymphomas and Hodgkin's disease, showing broad activity across various subtypes and demonstrating single-agent efficacy comparable to older treatments like alkylating agents and doxorubicin.

The drug works by inhibiting protein synthesis and topoisomerase II, allowing it to provide effective cytotoxicity without cross-resistance, and is integrated into multiple treatment protocols, enhancing the overall management of these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolving role of etoposide in the management of lymphomas and Hodgkin's disease. O'Reilly, SE., Klimo, P., Connors, JM.[2019]

In a study of 23 patients with aggressive B-cell non-Hodgkin lymphoma, the combination of rituximab with CODOX-M/IVAC showed promising efficacy, with 83% of low-risk and 71% of high-risk patients achieving complete remission after treatment.

The safety profile was acceptable, with no treatment-related deaths and manageable toxicity, including only two cases of grade 3 neutropenia, suggesting that this treatment combination is both effective and safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in combination with CODOX-M/IVAC: a retrospective analysis of 23 cases of non-HIV related B-cell non-Hodgkin lymphoma with proliferation index >95%. Mohamedbhai, SG., Sibson, K., Marafioti, T., et al.[2015]

Salvage chemotherapy followed by high-dose therapy and autologous stem cell transplantation is the standard treatment for relapsed diffuse large B-cell lymphoma, but the addition of rituximab has improved outcomes after first-line treatment and relapses.

The CORAL trial found no significant difference in response rates between two salvage regimens (R-ICE and R-DHAP), and identified that factors like early relapse and certain genetic markers significantly affect survival, indicating that over 70% of patients may not benefit from standard salvage therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there any role for transplantation in the rituximab era for diffuse large B-cell lymphoma? Gisselbrecht, C.[2022]

In a randomized trial of 118 patients with advanced diffuse lymphocytic lymphoma, the combination of the drug VP-16-213 with doxorubicin resulted in a higher complete remission rate of 54%, compared to 39% with VP-16-213 alone and 26% with VP-16-213 combined with cyclophosphamide.

The study found that combining VP-16-213 with cyclophosphamide led to significantly lower remission rates, suggesting that doxorubicin is a more effective partner for VP-16-213 in treating this type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

VP-16-213 in the treatment of stage III and IV diffuse lymphocytic lymphoma of the large cell (histiocytic) variety: an interim report. Jacobs, P., King, HS., Cassidy, F., et al.[2013]

The AMOPLACE chemotherapy regimen, which includes additional agents beyond the standard CHOP treatment, achieved a complete response rate of 68% in 60 patients with intermediate to high-grade non-Hodgkin's lymphomas, indicating its potential efficacy.

Despite its effectiveness, AMOPLACE was associated with significant myelosuppression, as 73% of patients experienced low white blood cell counts, and there were two treatment-related deaths, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AMOPLACE treatment of intermediate-grade and high-grade malignant lymphoma: a Cancer and Leukemia Group B study. Parker, BA., Santarelli, M., Green, MR., et al.[2017]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39897241/

Complete Remission of Plasmablastic Lymphoma With ... A mild regimen of cyclophosphamide, doxorubicin, vincristine, and prednisolone (mini-CHOP) normally utilized to treat large B-cell lymphoma was supplemented ...

2. trialx.com trialx.com/clinical-trials/listings/221520/a-study-of-daratumumab-and-dose-adjusted-epoch-in-plasmablastic-lymphoma/

A Study of Daratumumab and Dose-Adjusted EPOCH ... This feasibility trial studies how well daratumumab in combination with dose-adjusted etoposide, prednisone, vincristine sulfate, ...

3. jnjmedicalconnect.com jnjmedicalconnect.com/products/darzalex/medical-content/use-of-darzalex-in-plasmablastic-lymphoma

Use of DARZALEX in Plasmablastic Lymphoma Complete remission of plasmablastic lymphoma with daratumumab and a mild regimen of cyclophosphamide, doxorubicin, vincristine, and prednisolone ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2019-04794

A Study of Daratumumab and Dose-Adjusted EPOCH in ... Giving daratumumab may enhance the effectiveness of a standard chemotherapy (DA-EPOCH) in patients with plasmablastic lymphoma. Eligibility Criteria ...

5. ashpublications.org ashpublications.org/blood/article/144/21/2237/517403/Daratumumab-in-pediatric-relapsed-refractory-acute

Daratumumab in pediatric relapsed/refractory acute ... In cycle 1, patients with T-cell ALL/LL received daratumumab (16 mg/kg IV weekly on days 1, 8, 15, and 22) plus doxorubicin, vincristine, prednisone, pegylated- ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12141371/

Real-world data on the use of subcutaneous daratumumab ... Results from this noninterventional, multicenter, observational study provide evidence for the clinical efficacy and safety of daratumumab SC in ...

7. jnjmedicalconnect.com jnjmedicalconnect.com/products/darzalex-faspro/medical-content/darzalex-darzalex-faspro-adverse-event-hematologic-events-in-patients-with-newly-diagnosed-multip

Adverse Event - DARZALEX FASPRO® The most common grade 3/4 hematologic treatment-emergent adverse events (TEAEs) were neutropenia (43.8%), lymphopenia (31.3%), and thrombocytopenia (25.0%).

8. jnj.com jnj.com/innovativemedicine/emea/darzalex-daratumumab-subcutaneous-formulation-shows-51-percent-reduction-in-risk-of-progression-to-active-multiple-myeloma-for-patients-with-high-risk-smouldering-multiple-myeloma

DARZALEX® (daratumumab) subcutaneous formulation ... Overall survival was also extended with daratumumab SC, with 5-year survival rates of 93.0 percent vs 86.9 percent for active monitoring (HR, 0.52; 95.0 percent ...

9. aetna.com aetna.com/cpb/medical/data/900_999/0904.html?ref=counterforcehealth.org

Daratumumab (Darzalex) and Daratumumab and ... In the cohort that received 16 mg/kg, the median progression-free survival (PFS) was 5.6 months (95 % CI: 4.2 to 8.1), and 65 % (95 % CI: 28 to 86) of the ...

10. bloodcancerunited.org bloodcancerunited.org/resources/newsroom/fda-approval-new-treatment-indication-multiple-myeloma-drug

New Treatment Indication for Multiple Myeloma Drug Participants who received daratumumab plus hyaluronidase with Pd had significantly reduced risk of disease progression or death by 37% compared to participants ...