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

25 Participants Needed

Trial Summary

What is the purpose of this trial?

RATIONALE: Giving high-dose chemotherapy drugs, such as carmustine, etoposide, and cyclophosphamide, before a peripheral blood stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. After treatment, stem cells that were collected from the patient's blood are returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. PURPOSE: This clinical trial is studying the side effects of giving high-dose carmustine, etoposide, and cyclophosphamide together with a stem cell transplant and to see how well it works in treating patients with HIV-associated lymphoma.

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.

What data supports the effectiveness of the treatment involving chemotherapy and stem cell transplant for lymphoma?

Research shows that using high-dose chemotherapy drugs like cyclophosphamide, carmustine, and etoposide followed by autologous stem cell transplantation can lead to promising results in patients with aggressive non-Hodgkin's lymphoma, especially those who have partially responded to previous treatments or have relapsed. In some studies, complete responses were observed in a significant number of patients, indicating the potential effectiveness of this treatment approach. ^{1 2 3 4 5}

Is the chemotherapy and stem cell transplant treatment for lymphoma generally safe?

The treatment involving chemotherapy drugs like cyclophosphamide, carmustine, and etoposide, followed by autologous stem cell transplantation, has been studied for safety. It can be administered with acceptable toxicity, but there are risks such as interstitial pneumonitis (lung inflammation) and treatment-related mortality, especially at higher doses. Older patients may experience more severe side effects, including infections and cardiovascular issues. ^{1 4 6 7 8}

How does the treatment of chemotherapy combined with stem cell transplant for lymphoma differ from other treatments?

This treatment is unique because it combines high-dose chemotherapy drugs (carmustine, cyclophosphamide, and etoposide) with autologous stem cell transplantation, which uses the patient's own stem cells to help recover the bone marrow after intensive chemotherapy. This approach is particularly used for patients with aggressive or relapsed lymphoma, offering a potentially more effective option compared to standard chemotherapy alone. ^{1 2 4 5 9}

Research Team

Amrita Y. Krishnan, MD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. United States 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. [2017]

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

Prognostic factors for treatment outcome in autotransplantation of intermediate-grade and high-grade non-Hodgkin's lymphoma with cyclophosphamide, carmustine, and etoposide. [2017]

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

Limited efficacy of intensified preparative regimens and autologous transplantation as salvage therapy in high grade non-Hodgkin's lymphoma. [2019]

4. United States 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. [2017]

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

High-dose carmustine, etoposide, and cyclophosphamide followed by allogeneic hematopoietic cell transplantation for non-Hodgkin lymphoma. [2022]

6. England pubmed.ncbi.nlm.nih.gov

High-dose Bendamustine-EAM followed by autologous stem cell rescue results in long-term remission rates in lymphoma patients, without renal toxicity. [2018]

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

Toxicities of high-dose chemotherapy and autologous hematopoietic cell transplantation in older patients with lymphoma. [2021]

8. Japan pubmed.ncbi.nlm.nih.gov

LACE versus BEAM conditioning in relapsed and refractory lymphoma transplant: retrospective multicenter analysis of toxicity and efficacy. [2018]

9. Poland pubmed.ncbi.nlm.nih.gov

Comparable safety profile of BeEAM (bendamustine, etoposide, cytarabine, melphalan) and BEAM (carmustine, etoposide, cytarabine, melphalan) as conditioning before autologous haematopoietic cell transplantation. [2022]