Chemotherapy + Stem Cell Transplant for Lymphoma

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must be taking: Multi-drug regimen

Must not be taking: Azidothymidine

Disqualifiers: Active infection, CMV retinitis, others

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

Compensation: Varies

Number of Visits: 32

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether high-dose chemotherapy combined with a stem cell transplant can effectively treat lymphoma in patients who are also HIV-positive. Researchers aim to assess the treatment's effectiveness and understand any side effects. The treatment involves administering strong chemotherapy, including drugs like Carmustine, Cyclophosphamide, and Etoposide, to stop cancer cells from growing, followed by an autologous hematopoietic stem cell transplant to aid recovery. Suitable candidates for this trial have HIV and lymphoma, manage their HIV well with medication, and have shown certain responses to past lymphoma treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial requires participants to be on a multi-drug regimen for HIV, but they must stop taking AZT (zidovudine) before the stem cell transplant and for at least 2 months after. If you are taking AZT, you will need to switch to a different medication during this period.

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

A previous study showed that patients with lymphoma who received a transplant using their own stem cells had good long-term results, even among older adults. This suggests the treatment is generally well-tolerated.

Research on high-dose carmustine has shown it is often used in aggressive cancer treatments and can help some patients live longer. However, it may cause significant side effects that require careful management.

Cyclophosphamide, a common chemotherapy drug, can cause side effects like low white blood cell counts, increasing the risk of infections. Despite this, it effectively kills cancer cells.

Etoposide, another chemotherapy drug, has been studied with other treatments. It is generally safe but can also lower blood cell counts and raise infection risk.

Overall, these treatments have been used in cancer therapy and show promise, but they can have serious side effects. This trial is in its early phase, focusing on safety and finding the right dosage. Participants should discuss potential risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for lymphoma because it combines high-dose chemotherapy with a stem cell transplant, offering a unique approach that could improve outcomes. Unlike standard treatments that often rely solely on chemotherapy or radiation, this method uses autologous hematopoietic stem cell transplantation to restore bone marrow after intensive chemotherapy. The high-dose chemotherapy regimen, including carmustine, etoposide, and cyclophosphamide, aims to aggressively target cancer cells, while the stem cell transplant helps the body recover more rapidly. This combination has the potential to be more effective in wiping out cancer cells while minimizing long-term damage to healthy tissue.

What evidence suggests that this treatment might be an effective treatment for lymphoma?

Research has shown that high-dose chemotherapy followed by a transplant of a patient's own stem cells can effectively treat certain types of lymphoma. In this trial, participants will receive a combination of chemotherapy drugs—carmustine, etoposide, and cyclophosphamide—before undergoing an autologous stem cell transplant. Studies have found that this treatment can extend patients' lives and delay cancer recurrence. These chemotherapy drugs work together to destroy cancer cells and may also enhance the immune system's ability to fight the cancer. Many patients with lymphoma have experienced promising results, with many achieving remission, meaning no signs of the disease, after treatment. Although this approach is intense, it aims to cure the cancer, especially for those whose cancer responds well to chemotherapy. ^{1 3 6 7 8}

Who Is on the Research Team?

Amrita Y. Krishnan, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for HIV-positive patients with lymphoma who have less than 10% bone marrow involvement, normal liver function tests, and a controlled HIV viral load on specific medication regimens. They must not be pregnant or nursing, have no severe infections or AIDS-related symptoms that could complicate the transplant process, and should have adequate organ function.

Inclusion Criteria

I am mostly able to care for myself.

I am on a preventive treatment for a specific type of pneumonia due to low immune cells.

I cannot take AZT for at least 2 months after my transplant.

Exclusion Criteria

I do not have an ongoing bacterial or fungal infection.

I haven't had any AIDS-related infections in the past year, except for treatable conditions like Mycobacterium Avium, oral thrush, or herpes.

You have mental or emotional conditions that make it difficult for you to follow the study requirements.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis

Patients undergo leukapheresis to obtain peripheral blood stem cells for transplantation

1 week

1 visit (in-person)

High-dose Chemotherapy

Patients receive high-dose chemotherapy with carmustine, etoposide, and cyclophosphamide

1 week

Multiple visits (in-person)

Autologous PBSC Transplantation

Patients receive an autologous peripheral blood stem cell infusion

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Long-term

Follow-up at 30 days, 100 days, every 3 months for 1 year, every 6 months for 1 year, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Autologous Hematopoietic Stem Cell Transplantation
• Carmustine
• Cyclophosphamide
• Etoposide
• Peripheral Blood Stem Cell Transplantation

Trial Overview The study is testing high-dose chemotherapy drugs (carmustine, etoposide, cyclophosphamide) followed by returning the patient's own stem cells to treat cancer. The goal is to see how well this treatment works in patients with HIV-associated lymphoma and what side effects it may cause.

How Is the Trial Designed?

Group I: Treatment (high-dose chemotherapy, anti-HIV therapy) Experimental Treatment 6 Interventions

Patients undergo leukapheresis to obtain PBSCs for transplantation. At least 5 days later, patients with an adequate number of collected cells proceed to high-dose chemotherapy. Patients receive carmustine IV over 4 hours on days -7 to -5, etoposide IV over 4 hours on day -4, and cyclophosphamide IV on day -2. Patients receive an autologous PBSC infusion on day 0.

Autologous Hematopoietic Stem Cell Transplantation is already approved in United States, European Union for the following indications:

Approved in United States as Autologous Hematopoietic Stem Cell Transplantation for:

• Various hematologic malignancies including non-Hodgkin lymphoma, multiple myeloma, and leukemia

Approved in European Union as Autologous Stem Cell Transplant for:

• Non-Hodgkin lymphoma
• Multiple myeloma
• Leukemia
• Other hematologic malignancies

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study involving 464 patients with aggressive non-Hodgkin's lymphoma, the 3-year disease-free survival rate was 59% for those receiving high-dose chemotherapy followed by autotransplantation, compared to 52% for those receiving sequential chemotherapy, but this difference was not statistically significant (P = .46).

The overall 3-year survival rates were also similar between the two treatment groups, with 71% for sequential chemotherapy and 69% for autotransplantation, indicating that high-dose chemotherapy followed by autotransplantation does not provide a clear advantage over standard sequential chemotherapy for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of autologous bone marrow transplantation with sequential chemotherapy for intermediate-grade and high-grade non-Hodgkin's lymphoma in first complete remission: a study of 464 patients. Groupe d'Etude des Lymphomes de l'Adulte. Haioun, C., Lepage, E., Gisselbrecht, C., et al.[2017]

In a study of 346 lymphoma patients, those aged 70 and older experienced significantly higher rates of severe cardiovascular and skin toxicities from high-dose chemotherapy and autologous hematopoietic cell transplantation (AHCT) compared to younger patients aged 60 to 69.

Despite the effectiveness of the BEAM regimen followed by AHCT, older patients had a higher risk of nonrelapse mortality and progression or death, highlighting the need for strategies to reduce toxicities in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicities of high-dose chemotherapy and autologous hematopoietic cell transplantation in older patients with lymphoma. Dahi, PB., Lee, J., Devlin, SM., et al.[2021]

The maximum-tolerated dose (MTD) for the CBV regimen in 58 patients with refractory and relapsed lymphoma was determined to be cyclophosphamide 7,200 mg/m2, BCNU 450 mg/m2, and VP-16 2,000 mg/m2, with a notable increase in treatment-related mortality at higher doses.

Despite the high-risk nature of the patient population, the CBV regimen resulted in complete responses in 25% of patients with non-Hodgkin's lymphoma and 43% of patients with Hodgkin's disease, indicating its efficacy in achieving disease remission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyclophosphamide, carmustine, and etoposide with autologous bone marrow transplantation in refractory Hodgkin's disease and non-Hodgkin's lymphoma: a dose-finding study. Wheeler, C., Antin, JH., Churchill, WH., et al.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9375438/

Outcomes of Autologous Hematopoietic Cell Transplantation ... Data for outcomes after autologous hematopoietic cell transplant (auto-HCT) in DLBCL patients ≥70 years are limited. Auto-HCT is feasible on older DLBCL ...

2. ashpublications.org ashpublications.org/bloodadvances/article/9/13/3281/536427/Autologous-stem-cell-transplantation-for-relapsed

Autologous stem cell transplantation for relapsed/refractory ... Our results indicate that ASCT is a curative option for patients with chemosensitive disease especially in CR after salvage.

3. nature.com nature.com/articles/s41408-024-01085-9

Hematopoietic stem cell transplantation for DLBCL We examined the transplantation trends and outcomes for DLBCL patients undergoing auto-/allo-HSCT between 1990 and 2021 reported to EBMT.

4. link.springer.com link.springer.com/article/10.1007/s12672-025-01876-x

a meta-analysis | Discover Oncology Patients with malignant lymphoma who receive chemotherapy can substantially extend their overall survival and progression-free survival rates with AHSCT ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4511149/

Autologous Hematopoietic Stem Cell Transplantation—10 ... The objective of the present study was to evaluate the outcomes of patients with mainly lymphoma and multiple myeloma after autologous stem cell transplant.

6. ascopubs.org ascopubs.org/doi/10.1200/GO.21.00383

Long-Term Outcomes and Safety Trends of Autologous ... It is feasible to achieve comparable short- and long-term outcomes in patients with NHL undergoing ASCT in a resource-poor country with improved supportive ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5947447/

Autologous Stem Cell Transplantation in Elderly Lymphoma ... This retrospective study showed favorable transplant outcomes, including survival and toxicity, in a large cohort of lymphoma patients over 70 years of age who ...

8. nature.com nature.com/articles/s41582-024-01050-x

Autologous haematopoietic stem cell transplantation for ... Long-term outcomes in a large cohort of patients treated with AHSCT for MS were first reported in a retrospective joint analysis of the EBMT and ...