Chemotherapy + Stem Cell Transplant for Lymphoma

Not currently recruiting at 127 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alliance for Clinical Trials in Oncology

Disqualifiers: Non-cns nhl, Prior chemotherapy, Organ transplant, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of chemotherapy combined with a stem cell transplant compared to chemotherapy alone for treating primary CNS B-cell lymphoma, a type of brain cancer with no established best treatment. The trial aims to assess the positive and negative effects of these treatments on the condition. Individuals diagnosed with primary CNS diffuse large B-cell lymphoma through a brain biopsy or fluid tests, who have not yet received chemotherapy or radiation, may be suitable candidates for this trial. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to important research.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since the trial involves chemotherapy and stem cell transplant, it's best to discuss your current medications with the trial team to ensure there are no interactions.

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

Research has shown that treatments using carmustine, cytarabine, and thiotepa carry some risks, but these are generally manageable. Carmustine may cause serious lung and heart problems, particularly at high doses. Cytarabine often results in blood-related side effects, with severe cases occurring in up to 87% of patients. Thiotepa is usually well-tolerated but can reduce blood cell production.

Autologous stem cell transplants, which use a patient's own stem cells, have been linked to better survival rates and fewer non-cancer-related deaths. However, a small risk of early death remains due to treatment side effects or disease progression.

Overall, while these treatments involve risks, studies indicate that they can be controlled and monitored to help maintain patient safety during treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the chemotherapy and stem cell transplant approach for lymphoma because it combines potent chemotherapy drugs—Carmustine, Cytarabine, and Thiotepa—with the regenerative power of stem cells. This treatment is distinctive because, unlike traditional chemotherapy alone, which often targets cancer cells but can also harm healthy cells, the stem cell transplant aims to restore and rebuild the patient's immune system after chemotherapy. By integrating these components, the treatment has the potential to enhance recovery and improve outcomes more effectively than standard chemotherapy regimens.

What evidence suggests that this trial's treatments could be effective for primary CNS B-cell lymphoma?

Research has shown that certain chemotherapy drugs, such as Carmustine, Cytarabine, and Thiotepa, hold promise for treating lymphoma. In this trial, participants in one arm will undergo induction therapy followed by a stem cell transplant using their own stem cells, which has been associated with good survival rates and fewer deaths unrelated to cancer recurrence. Participants in another arm will receive induction therapy followed by consolidation chemotherapy. Carmustine is often used in standard treatments and has extended survival for some patients. Cytarabine has been linked to longer periods without disease progression. Thiotepa-based treatments have demonstrated better results in preventing disease progression compared to other treatments. Overall, these treatments have shown positive results in various studies, making them promising options for lymphoma therapy. ^{2 3 5 6 7}

Who Is on the Research Team?

Tracy Batchelor, MD, MPH

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with primary CNS B-cell lymphoma, no history of other non-Hodgkin lymphomas or prior treatments. Participants must have a Karnofsky score indicating they can care for themselves and not be pregnant or nursing. They should test negative for HIV, hepatitis, and agree to use effective contraception.

Inclusion Criteria

I am mostly independent but may need assistance for some daily activities.

My diagnosis of brain lymphoma was confirmed through a biopsy or fluid tests.

I have not had chemotherapy or radiation for lymphoma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Patients undergo induction therapy for five cycles as defined in the protocol

15-20 weeks

Consolidation Chemotherapy

Patients receive either myeloablative consolidation treatment with HDT/ASCT or non-myeloablative consolidation chemotherapy with cytarabine and etoposide

4-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Autologous Stem Cell Transplant
• Carmustine
• Cytarabine
• Thiotepa

Trial Overview The study compares the effects of chemotherapy alone versus chemotherapy followed by an autologous stem cell transplant in treating central nervous system B-cell lymphoma. The goal is to determine which treatment approach is more beneficial.

How Is the Trial Designed?

Group I: Arm II Experimental Treatment 3 Interventions

Patients undergo induction therapy for five cycles as defined in the protocol. Patients undergo consolidation chemotherapy.

Group II: Arm I Experimental Treatment 4 Interventions

Patients undergo induction therapy for five cycles as defined in the protocol. Patients undergo stem cell transplant.

Carmustine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as BiCNU for:

• Brain tumors
• Multiple myeloma
• Hodgkin's disease
• Non-Hodgkin's lymphoma

Approved in European Union as Carmubris for:

• Brain tumors
• Multiple myeloma
• Hodgkin's disease
• Non-Hodgkin's lymphoma

Approved in Canada as BCNU for:

• Brain tumors
• Multiple myeloma
• Hodgkin's disease
• Non-Hodgkin's lymphoma

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The TECAM conditioning regimen, which includes thiotepa and cyclophosphamide, showed comparable efficacy and safety to the conventional BEAM regimen in a study of 125 patients undergoing autologous stem cell transplantation for B-cell lymphomas, with 3-year progression-free survival rates of 49% for TECAM and 62% for BEAM.

TECAM was particularly effective for older patients, with 23% of TECAM recipients over 65 years old achieving similar outcomes to younger patients, suggesting it may be a suitable option for older individuals who have had more prior treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Replacing carmustine by thiotepa and cyclophosphamide for autologous stem cell transplantation in Hodgkin's and non-Hodgkin's B-cell lymphoma. Joffe, E., Rosenberg, D., Rozovski, U., et al.[2019]

In a study of 101 lymphoma patients undergoing autologous stem cell transplantation, the mitoxantrone-melphalan (Mx-Mel) regimen showed similar efficacy to the BEAM regimen while being less toxic, making it a promising alternative for patients who cannot tolerate high cytotoxic treatments.

Although the BEAM regimen resulted in a statistically shorter time to neutrophil engraftment (10 days) compared to Mx-Mel (12 days), both regimens did not lead to significant differences in transplant-related complications, indicating that Mx-Mel is a safe option with effective outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Mitoxantrone-Melphalan and BEAM Conditioning Regimens in Patients with Lymphoma. Gunes, AK., Serin, I., Demir, I., et al.[2023]

In a phase I study involving 40 patients with refractory solid tumors or non-Hodgkin's lymphoma, a combination of high-dose cyclophosphamide, thiotepa, and carmustine (BCNU) followed by autologous stem cell rescue resulted in a 63% overall response rate, indicating significant efficacy in reducing tumor burden.

However, the treatment was associated with serious safety concerns, including a 20% early death rate due to toxic effects like sepsis and respiratory failure, particularly at higher doses of BCNU, which limits its use in heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose tri-alkylator chemotherapy with autologous stem cell rescue in patients with refractory malignancies. Moormeier, JA., Williams, SF., Kaminer, LS., et al.[2019]

In a study involving 14,544 patients, thiotepa-based preparative regimens for autologous stem cell transplantation showed no significant differences in survival outcomes compared to the standard BEAM regimen for diffuse large B-cell lymphoma, follicular lymphoma, and Hodgkin lymphoma.

The rates of common complications, including infections and secondary malignancies, were similar between patients treated with thiotepa and those treated with BEAM, suggesting that thiotepa could be a safe and effective alternative for high-dose therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thiotepa-based high-dose therapy for autologous stem cell transplantation in lymphoma: a retrospective study from the EBMT. Sellner, L., Boumendil, A., Finel, H., et al.[2023]

In a retrospective study of 56 patients with primary central nervous system lymphoma (PCNSL) undergoing autologous stem cell transplant (ASCT), there was no significant difference in progression-free survival or overall survival between those receiving thiotepa-based conditioning and those receiving BEAM conditioning, despite the thiotepa group having higher-risk disease features.

The study found that the disease response status before transplant was a critical factor influencing outcomes, with patients in complete remission showing significantly better overall survival rates compared to those with partial response, highlighting the importance of pre-transplant disease status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Autologous Stem Cell Transplant Consolidation in Primary Central Nervous System Lymphoma: A Mayo Clinic Experience. Khurana, A., Micallef, IN., LaPlant, BR., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5607634/

A review of autologous stem cell transplantation in ... Outcomes were similar for primary refractory and poor-risk/relapsed HL. For patients with chemotherapy-resistant disease, the 46% 5-year OS rate was achieved ...

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

Autologous stem cell transplantation for relapsed/refractory ... After a median follow-up of 74 months from infusion, 65% were alive and 84% free of disease.

3. astctjournal.org astctjournal.org/article/S2666-6367(22)01838-3/fulltext

Outcomes of Older Adults with Non-Hodgkin Lymphoma ... Nonrelapse mortality after autologous stem cell transplantation (ASCT) in older patients with lymphoma was low and has improved over time.

4. nature.com nature.com/articles/s41408-023-00868-w

Real-world data of long-term survival in patients with T-cell ... This study retrospectively analyzed data from 598 patients who underwent transplantation for T-cell lymphomas from 2010 to 2020. In total, 317 ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2666636722018383

Outcomes of Older Adults with Non-Hodgkin Lymphoma ... Nonrelapse mortality after autologous stem cell transplantation (ASCT) in older patients with lymphoma was low and has improved over time.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9302266/

Long-Term Outcomes and Safety Trends of Autologous Stem ... The overall 5-year event-free survival and overall survival are 43.5% and 47.6%, respectively, in patients with NHL undergoing ASCT over the ...

7. asco.org asco.org/abstracts-presentations/ABSTRACT182277

Safety and efficacy of autologous stem cell transplantation ... Three patients had early mortality (within 100 days) from rapid disease progression (n=1) or treatment toxicity (n=2). Median follow up for survivors was 23 ...