Chemotherapy + Pomalidomide for HIV-Associated Lymphoma

Overseen By Ramya M Ramaswami, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must be taking: ART, Antivirals

Must not be taking: Investigational agents

Disqualifiers: Brain involvement, Heart failure, others

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

Compensation: Varies

Number of Visits: 7

Duration: 18 weeks

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of a new drug, pomalidomide, when combined with chemotherapy drugs such as cyclophosphamide, doxorubicin, etoposide, prednisone, and vincristine, and in some cases, rituximab, for treating non-Hodgkin lymphoma (NHL) in individuals with HIV. NHL is a common cancer among those with HIV, and the study seeks to improve treatment options. It targets adults with HIV-associated B-cell NHL who have specific high-risk features, such as certain tumor types or symptoms of brain involvement. Participants will undergo multiple treatment cycles involving both oral and IV medications. This research could offer new hope for those facing this challenging combination of health issues. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, providing participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must be willing to take and adhere to antiretroviral therapy (ART) and cannot receive investigational agents from other clinical trials.

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

Previous studies have shown pomalidomide to be a safe treatment option. It has been used successfully for Kaposi's Sarcoma (KS) in individuals with or without HIV and is known as a chemotherapy-sparing agent, reducing the need for strong chemotherapy drugs. Most people tolerate pomalidomide well, with manageable side effects.

In this trial, pomalidomide combines with various chemotherapy drugs, including cyclophosphamide, doxorubicin, etoposide, prednisone, and vincristine. These drugs are commonly used in cancer treatment and are generally well understood in terms of safety. Although chemotherapy can cause side effects, doctors closely monitor patients to manage these effects and adjust treatment as needed.

As this trial is in an early phase, it primarily focuses on testing safety. Researchers are carefully studying the combination of pomalidomide with these chemotherapy drugs to ensure it is safe for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine chemotherapy with pomalidomide, a drug that modulates the immune system. Unlike standard HIV-associated lymphoma treatments, which typically involve chemotherapy alone, the addition of pomalidomide aims to enhance the body's immune response against cancer cells. Additionally, the trial explores varying doses of pomalidomide to determine the most effective and safe level, potentially leading to improved outcomes. This unique approach could offer a more targeted and powerful way to combat lymphoma in patients living with HIV.

What evidence suggests that this trial's treatments could be effective for HIV-associated lymphoma?

Research has shown that pomalidomide effectively treats conditions related to HIV, such as Kaposi sarcoma, with good results and safety. In some studies, over 70% of patients taking pomalidomide responded well to the treatment. This trial will investigate pomalidomide combined with chemotherapy for HIV-related lymphoma. Participants will receive pomalidomide alongside chemotherapy drugs like prednisone, etoposide, doxorubicin, and vincristine. These chemotherapy drugs have a history of effectively treating lymphomas. Combining these treatments aims to attack cancer cells more aggressively and may improve outcomes for patients with HIV-related non-Hodgkin lymphoma. ^{1 5 6 7 8}

Who Is on the Research Team?

Ramya M Ramaswami, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults over 18 with HIV-associated B-cell non-Hodgkin lymphoma and high-risk features, who can take daily aspirin or substitutes, have not had prior curative-intent chemo (except as a bridge to therapy), are willing to adhere to antiretroviral therapy, and if applicable, use two forms of birth control. Must have proper organ/marrow function unless issues are due to lymphoma/HIV.

Inclusion Criteria

I have not had chemotherapy aimed at curing my lymphoma.

Persons of childbearing potential must have a negative pregnancy test and commit to birth control measures

Participants must understand and sign a written informed consent document

Exclusion Criteria

Known procoagulant disorders excluding specific exceptions

Pregnant or breastfeeding persons

Ejection fraction less than 40% by echocardiography

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive up to 6 cycles of treatment with pomalidomide and chemotherapy drugs, with or without rituximab

18 weeks

Every 3 weeks for 6 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 3 months for the first year, then every 6 months for 4 years

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Doxorubicin
• Etoposide
• Pomalidomide
• Prednisone
• Rituximab
• Vincristine

Trial Overview The trial tests pomalidomide combined with chemotherapy drugs (cyclophosphamide, vincristine, prednisone, doxorubicin, etoposide) and possibly rituximab in people with HIV-related B-cell NHL. Participants will undergo up to six cycles of treatment involving oral medication and IV chemotherapy.

How Is the Trial Designed?

Group I: 2/Dose Expansion Experimental Treatment 7 Interventions

Pomalidomide (at the MTD) + Prednisone, Etoposide, Doxorubicin, Vincristine and

Group II: 1/Dose Escalation Experimental Treatment 7 Interventions

Pomalidomide (escalating doses) + Prednisone, Etoposide, Doxorubicin, Vincristin

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

In a study of 37 patients with poor-prognosis AIDS-related non-Hodgkin's lymphoma, a reduced-dose chemotherapy regimen combined with zidovudine resulted in a 52% objective response rate, indicating some efficacy in this high-risk population.

However, the treatment was associated with significant bone marrow toxicity, leading to two treatment-related deaths, highlighting the need for careful monitoring and management of side effects in this vulnerable group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective study with combined low-dose chemotherapy and zidovudine in 37 patients with poor-prognosis AIDS-related non-Hodgkin's lymphoma. French-Italian Cooperative Study Group. Tirelli, U., Errante, D., Oksenhendler, E., et al.[2020]

In a study of 43 people living with HIV undergoing chemotherapy for Burkitt lymphoma, the elimination half-life of high-dose methotrexate (MTX) was found to be 21.7 hours on average, indicating consistent drug clearance.

Despite concerns about potential interactions between methotrexate and antiretroviral therapies, particularly tenofovir, the study found no significant impact on MTX elimination kinetics, suggesting that these treatments can be safely managed together.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacokinetics of high-dose methotrexate in people living with HIV on antiretroviral therapy. Dalla Pria, A., Bendle, M., Ramaswami, R., et al.[2018]

In a study of 18 HIV-infected patients with lymphoma, 44.4% experienced high mortality rates, and only 11.1% achieved a complete response to treatment, indicating poor outcomes for this group.

The majority of patients presented with advanced stages of lymphoma (III-IV) and common symptoms like bulky masses and extra-nodal involvement, suggesting that HIV-related lymphoma tends to be aggressive and challenging to treat.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HIV-related lymphomas in adults served in the public health network: An observational study. da Silva Nascimento, J., Sérgio Ramos de Araújo, P., Romão de Souza Júnior, V., et al.[2022]

In a dose-escalation trial involving 47 patients with aggressive HIV-related non-Hodgkin's lymphoma, the maximum tolerated doses of doxorubicin and etoposide were not reached, indicating that the chemotherapy regimen was well-tolerated even when combined with antiretroviral therapy.

The treatment resulted in a 30% complete response rate and a 28% overall survival rate at 42 months, suggesting that the VACOP-B regimen is an effective option for managing this type of lymphoma in HIV-infected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective, non-randomised phase 1-2 trial of VACOP-B with filgrastim support for HIV-related non-Hodgkin's lymphoma. Sawka, CA., Shepherd, FA., Franssen, E., et al.[2015]

In a study of 19 HIV patients undergoing chemotherapy for non-Hodgkin's lymphoma, HAART did not significantly alter the pharmacokinetics of doxorubicin (DOX), suggesting that the way the body processes DOX remains consistent regardless of HAART treatment.

However, the area under the concentration curve (AUC) of DOX was linked to higher levels of hematologic toxicity in patients receiving CHOP alone, indicating that other factors may contribute to increased toxicity when HAART is also administered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of highly active antiretroviral therapy (HAART) on pharmacokinetics and pharmacodynamics of doxorubicin in patients with HIV-associated non-Hodgkin's lymphoma. Toffoli, G., Corona, G., Cattarossi, G., et al.[2020]

In a study of 60 previously untreated patients with intermediate- or high-grade non-Hodgkin's lymphomas, the combination chemotherapy regimen CEOP-B/VIMB achieved a high complete remission rate of 77% and a 48-month overall survival rate of 70%.

The treatment demonstrated mild toxicity, making it a favorable option compared to third-generation regimens, while patient outcomes were significantly influenced by factors such as serum LDH levels and performance status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CEOP-B alternated with VIMB in intermediate-grade and high-grade non-Hodgkin's lymphoma: a pilot study. De Lena, M., Ditonno, P., Lorusso, V., et al.[2017]

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 91 people living with HIV and Burkitt lymphoma, adding rituximab to CODOX-M/IVAC chemotherapy did not increase severe treatment-related toxicities, indicating it is a safe option for this population.

The addition of rituximab significantly improved both overall survival (72% vs. 55%) and progression-free survival (81% vs. 55%) compared to chemotherapy alone, suggesting it enhances treatment efficacy without added risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adding rituximab to CODOX-M/IVAC chemotherapy in the treatment of HIV-associated Burkitt lymphoma is safe when used with concurrent combination antiretroviral therapy. Alwan, F., He, A., Montoto, S., et al.[2022]

A modified chemotherapy regimen for Burkitt lymphoma in HIV-positive patients, which included rituximab and adjustments to drug dosages, resulted in a lower rate of severe toxicities (grade 3 to 4) at 79%, compared to 100% in the original regimen, while avoiding severe mucositis.

The treatment showed promising outcomes with a 1-year progression-free survival rate of 69% and overall survival rate of 72%, indicating that the modified regimen is effective for this high-risk population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AMC 048: modified CODOX-M/IVAC-rituximab is safe and effective for HIV-associated Burkitt lymphoma. Noy, A., Lee, JY., Cesarman, E., et al.[2022]

Liposomal doxorubicin combined with cyclophosphamide, vincristine, and prednisone showed an impressive overall response rate of 88% in patients with AIDS-related non-Hodgkin's lymphoma, with 75% achieving complete remissions, indicating its efficacy as a treatment option.

The study found that effective HIV viral control during chemotherapy significantly improved survival rates, although complete remissions were achieved regardless of HIV viral control or the expression of the MDR-1 resistance marker, suggesting that liposomal doxorubicin may effectively bypass this resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposome-encapsulated doxorubicin in combination with standard agents (cyclophosphamide, vincristine, prednisone) in patients with newly diagnosed AIDS-related non-Hodgkin's lymphoma: results of therapy and correlates of response. Levine, AM., Tulpule, A., Espina, B., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8898289/

Safety, activity, and long-term outcomes of pomalidomide in ... Conclusion: Pomalidomide is a safe and active chemotherapy-sparing agent for the treatment of KS among individuals with or without HIV. Keywords: ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33608378/

Use of pembrolizumab with or without pomalidomide in HIV ... The progression-free survival was 4.1 months (95% CI: 1.3 to 12.4) and overall survival was 14.7 months (95% CI: 2.96 to not reached). Three patients with PEL ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)01356-5/fulltext

MO41-5 Efficacy of pomalidomide in patients with kaposi ... R. Ramaswami et al and M. N. Polizzoto et al found that overall response rates were 71% and 73%, respectively, with HIV-negative patients showing more favorable ...

4. ccr.cancer.gov ccr.cancer.gov/news/article/fda-approves-pomalidomide-for-aids-related-kaposi-sarcoma

FDA approves pomalidomide for AIDS-related Kaposi sarcoma “Pomalyst has shown positive results in Kaposi sarcoma ... HIV-associated primary central nervous system lymphoma. Return to top ...

5. aol.amegroups.org aol.amegroups.org/article/view/7431/html

HIV-associated lymphoma—advances in clinical management The French lymphoma research groups reported on outcomes with RCHOP. In a sub-analysis of 52 PLWH with DLBCL, 85% received RCHOP with similar outcomes to HIV- ...

6. aacrjournals.org aacrjournals.org/clincancerres/article-abstract/28/5/840/681694

Safety, Activity, and Long-term Outcomes of Pomalidomide in ... Pomalidomide is a safe and active chemotherapy-sparing agent for the treatment of KS among individuals with or without HIV.

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)00729-4/fulltext

Human immunodeficiency virus-associated lymphomas Although the prognosis of PBL is generally reported as poor, long-term survival can be achieved. In an analysis of 135 patients, OS was better ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7898875/

Use of pembrolizumab with or without pomalidomide in HIV ... The progression-free survival was 4.1 months (95% CI: 1.3 to 12.4) and overall survival was 14.7 months (95% CI: 2.96 to not reached). Three ...