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

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

Trial Summary

What is the purpose of this trial?

This trial studies how well daratumumab combined with chemotherapy works in treating patients with a specific type of lymphoma. The treatment targets cancer cells with a protein called CD38, helping the immune system attack them and stopping their growth. Daratumumab is a CD38 monoclonal antibody approved for treating relapsed/refractory and newly diagnosed multiple myeloma.

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.

What data supports the effectiveness of the drug combination Daratumumab + Chemotherapy for Lymphoma?

Research shows that combining doxorubicin with etoposide (VP-16-213) leads to higher complete remission rates in lymphoma patients compared to using cyclophosphamide with etoposide. This suggests that doxorubicin, a component of the treatment, is effective in treating lymphoma. ^{1 2 3 4 5}

Is the combination of Daratumumab and chemotherapy generally safe for humans?

The safety of chemotherapy drugs like cyclophosphamide, doxorubicin, etoposide, and prednisone has been evaluated in various studies for different types of lymphoma. These studies generally report manageable toxicity and no treatment-related deaths, indicating that these drugs are generally safe when used in combination for lymphoma treatment. ^{3 4 6 7 8}

What makes the drug combination of Daratumumab and Chemotherapy unique for treating lymphoma?

This treatment combines Daratumumab, a monoclonal antibody that targets cancer cells, with a chemotherapy regimen including Cyclophosphamide, Doxorubicin, Etoposide, and Prednisone. This combination is unique because it integrates Daratumumab, which is not typically part of standard lymphoma treatments like R-CHOP, potentially offering a novel mechanism of action by enhancing the immune system's ability to fight cancer. ^{5 9 10 11 12}

Research Team

Ariela Noy, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Ricardo Attar

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology, University of Buenos Aires

Dr. Anastasia G. Daifotis

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2023

MD

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

Findings from Research

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]

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 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]

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 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 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]

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]

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 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]

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]

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]

References

1. United States 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. [2013]

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

VP-16-213 in the treatment of stage III and IV diffuse large cell lymphoma. [2019]

3. England 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. [2015]

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

The evolving role of etoposide in the management of lymphomas and Hodgkin's disease. [2019]

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

A dose-finding study of liposomal daunorubicin with CVP (COP-X) in advanced NHL. [2020]

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

Efficacy and toxicity of liposomal daunorubicin included in PVABEC regimen for aggressive NHL of the elderly. [2019]

7. China 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. [2023]

8. England 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%. [2015]

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

Outcomes in patients with aggressive B-cell non-Hodgkin lymphoma after intensive frontline treatment failure. [2020]

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

AMOPLACE treatment of intermediate-grade and high-grade malignant lymphoma: a Cancer and Leukemia Group B study. [2017]

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

Nursing Alchemy: Transforming R-CHOP Information Into Essentials. [2023]

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

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