Chemotherapy + Pomalidomide for HIV-Associated Lymphoma

Recruiting in Palo Alto (17 mi)

Overseen by Kathryn A Lurain, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

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

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests a combination of pomalidomide and chemotherapy, with or without rituximab, in adults with HIV and high-risk B-cell non-Hodgkin lymphoma. Pomalidomide boosts the immune system and helps increase important immune cells. The goal is to find the safest and most effective dose for this 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.

What data supports the effectiveness of the drug combination used in the Chemotherapy + Pomalidomide for HIV-Associated Lymphoma trial?

Research shows that adding rituximab to a similar chemotherapy regimen (CODOX-M/IVAC) for HIV-associated Burkitt lymphoma is safe and suggests survival benefits. Additionally, etoposide, a component of the treatment, has shown broad activity in managing various types of lymphomas, indicating its potential effectiveness in this combination. ^{1 2 3 4 5}

Is the combination of chemotherapy drugs and Pomalidomide safe for treating HIV-associated lymphoma?

Research shows that adding rituximab to chemotherapy regimens like CODOX-M/IVAC is safe for people with HIV-associated lymphoma when used with antiretroviral therapy. Liposomal doxorubicin combined with standard chemotherapy agents has been evaluated for safety in AIDS-related non-Hodgkin's lymphoma, and a study found that the maximum tolerated doses of etoposide and doxorubicin were not exceeded, indicating a manageable safety profile. ^{1 5 6 7 8}

What makes the chemotherapy and pomalidomide drug combination unique for treating HIV-associated lymphoma?

This treatment combines chemotherapy drugs with pomalidomide, which is not commonly used in standard regimens for HIV-associated lymphoma. Pomalidomide is an immunomodulatory drug that can enhance the immune system's ability to fight cancer, potentially offering a novel approach for patients with HIV-associated lymphoma who may have compromised immune systems. ^{1 3 9 10 11}

Research Team

Kathryn A Lurain, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• Cyclophosphamide (Alkylating agents)
• Doxorubicin (Anti-tumor antibiotic)
• Etoposide (Topoisomerase I inhibitors)
• Pomalidomide (Immunomodulatory Agent)
• Prednisone (Corticosteroid)
• Rituximab (Monoclonal Antibodies)
• Vincristine (Vinca alkaloids)

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.

Participant Groups

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 Canada, Japan for the following indications:

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+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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]

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]

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 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]

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]

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]

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 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]

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]

References

1. England 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. [2022]

2. England 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. [2020]

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

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

4. 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]

5. Netherlands 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. [2015]

6. United States 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. [2018]

7. England 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. [2020]

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

CEOP-B alternated with VIMB in intermediate-grade and high-grade non-Hodgkin's lymphoma: a pilot study. [2017]

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

HIV-related lymphomas in adults served in the public health network: An observational study. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

The pharmacokinetics of high-dose methotrexate in people living with HIV on antiretroviral therapy. [2018]

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

AMC 048: modified CODOX-M/IVAC-rituximab is safe and effective for HIV-associated Burkitt lymphoma. [2022]