Chemotherapy + Stem Cell Transplant for Lymphoma

Recruiting at 125 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

113 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The purpose of this study is to find out what effects (good and/or bad) treatment with chemotherapy and stem cell transplant compared with chemotherapy alone will have on primary CNS B-cell lymphoma. Currently the best treatment for patients with primary CNS B-cell lymphoma is not known.

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 the chemotherapy and stem cell transplant treatment generally safe for humans?

The treatment involving chemotherapy and autologous stem cell transplant has been studied for safety. In one study, replacing carmustine with thiotepa and cyclophosphamide showed similar safety profiles, even in older patients. However, high-dose regimens can lead to serious side effects like lung disease and infections, with a 20% early death rate due to toxic effects in some cases. ^{1 2 3 4 5}

How does the chemotherapy drug combination of Carmustine, Cytarabine, and Thiotepa differ from other treatments for lymphoma?

This treatment is unique because it combines high-dose chemotherapy drugs with a stem cell transplant, aiming to aggressively target lymphoma cells. Unlike some other regimens, it includes Thiotepa, which is less commonly used in standard protocols, potentially offering a different mechanism of action or side effect profile. ^{5 6 7 8 9}

What data supports the effectiveness of the treatment Autologous Stem Cell Transplant with Carmustine, Cytarabine, and Thiotepa for Lymphoma?

Research shows that thiotepa-based conditioning regimens, which include drugs like carmustine and cytarabine, have comparable effectiveness and safety to traditional regimens in treating lymphomas, even in older patients. This suggests that the combination used in the trial could be effective for lymphoma treatment. ^{1 2 3 5 10}

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

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]

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 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 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]

Citations

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

Outcomes of Autologous Stem Cell Transplant Consolidation in Primary Central Nervous System Lymphoma: A Mayo Clinic Experience. [2021]

2. England 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. [2019]

3. England pubmed.ncbi.nlm.nih.gov

BendaEAM versus BEAM as conditioning regimen for ASCT in patients with relapsed lymphoma (BEB): a multicentre, randomised, phase 2 trial. [2023]

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

High-dose tri-alkylator chemotherapy with autologous stem cell rescue in patients with refractory malignancies. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Thiotepa-based high-dose therapy for autologous stem cell transplantation in lymphoma: a retrospective study from the EBMT. [2023]

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

Topical carmustine (BCNU) in the treatment of mycosis fungoides. [2019]

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

Impact of Implementing a Bendamustine-Based Conditioning Regimen on Outcomes of Autologous Stem Cell Transplantation in Lymphoma while Novel Cellular Therapies Emerge. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Z-BeEAM (Ibritumomab tiuxetan, Bendamustine, Etoposide, Cytarabine, Melphalan) before autologous stem cell transplantation is safe and efficient for refractory large B-cell lymphoma. [2020]

9. Saudi Arabia pubmed.ncbi.nlm.nih.gov

Comparison of Mitoxantrone-Melphalan and BEAM Conditioning Regimens in Patients with Lymphoma. [2023]

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

Mini-BEAM as salvage therapy for relapsed or refractory Hodgkin's disease before intensive therapy and autologous bone marrow transplantation. [2017]