Auto Stem Cell Transplant for Lymphoma

Overseen By Timothy Krepski

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Masonic Cancer Center, University of Minnesota

Must be taking: Anti-HIV therapy

Disqualifiers: Pregnancy, Chemotherapy resistance, Active infection, 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

Duration: 4-6 weeks

150 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are HIV positive, you must be on a maximally active anti-HIV regimen as determined by your doctor.

What data supports the effectiveness of the treatment Auto Stem Cell Transplant for Lymphoma?

Research shows that high-dose chemotherapy followed by autologous stem cell transplantation is effective for treating relapsed or refractory Hodgkin and non-Hodgkin lymphoma, with studies reporting high survival rates and disease-free progression. The BEAM regimen, which includes carmustine and melphalan, is commonly used and has shown similar effectiveness to other regimens with potentially less toxicity. ^{1 2 3 4 5}

Is the auto stem cell transplant for lymphoma generally safe for humans?

The safety of auto stem cell transplants for lymphoma has been studied, showing that while effective, high-dose chemotherapy regimens can lead to significant side effects. These include organ toxicity, such as liver and kidney issues, and other complications like mucositis (painful inflammation and ulceration of the mucous membranes lining the digestive tract). However, newer formulations like EVOMELA have shown an acceptable safety profile with reduced complications. ^{3 6 7 8 9}

How is the Auto Stem Cell Transplant for Lymphoma treatment different from other treatments?

This treatment is unique because it combines high-dose chemotherapy with drugs like BCNU (carmustine), cyclophosphamide, and melphalan, along with total body irradiation and peripheral blood stem cell transplantation, which helps restore the patient's blood cells after intensive treatment. This approach is particularly used for patients with relapsed or refractory lymphoma, offering a comprehensive strategy to eliminate cancer cells and support recovery. ^{3 5 10 11 12}

What is the purpose of this trial?

This is a phase II study of autologous transplant for patients with Hodgkin (HL) and non-Hodgkin lymphomas (NHL) including those who are HIV positive.

Research Team

Veronika Bachanova, MD

Principal Investigator

Masonic Cancer Center, University of Minnesota

Eligibility Criteria

This trial is for lymphoma patients, including those with HIV, who have not responded well to previous treatments. They must be in good physical condition (Karnofsky/Lansky score ≥80%), without severe liver disease or serious organ dysfunction. Eligible participants include those with various types of lymphoma such as Mature T-Cell and Mantle Cell Lymphoma after certain responses to therapy, and specific criteria are set for Hodgkin's Lymphoma stages and treatment responses.

Inclusion Criteria

My Lymphoblastic Lymphoma is in second or later complete remission or in first or later partial remission.

I have Mature T-Cell Lymphoma and have undergone initial therapy.

I have Hodgkin Lymphoma and my previous treatments didn't work.

Exclusion Criteria

Pregnant or breastfeeding females

Patients eligible for any higher priority transplant protocols

My cancer did not respond to chemotherapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive autologous stem cell transplant with either BEAM, CBV, or CY/TBI regimens

4-6 weeks

Engraftment

Monitoring for platelet and neutrophil engraftment

Up to engraftment

Follow-up

Participants are monitored for progression-free survival, overall survival, and secondary malignancies

3 years

Treatment Details

Interventions

• BCNU
• Cyclophosphamide
• Melphalan
• Peripheral blood stem cell transplantation
• Total Body Irradiation

Trial Overview The study tests autologous stem cell transplantation combined with chemotherapy drugs like Etoposide, AraC, G-CSF, Cyclophosphamide, BCNU, Melphalan and procedures like Total Body Irradiation on patients with Hodgkin's and non-Hodgkin's lymphomas. It aims to see how effective this approach is for those who haven't had success with other treatments.

Participant Groups

Group I: CY/TBI Experimental Treatment 4 Interventions

Cyclophosphamide/Total Body Irradiation (CY/TBI) for patients with recent history of CNS lymphoma or those with allergies/contra-indications to agents used in BEAM

Group II: CBV: HL Experimental Treatment 3 Interventions

Cyclophosphamide, BCNU and VP-16 (CBV) for HL patients

Group III: BEAM: NHL & HL Experimental Treatment 6 Interventions

BCNU, etoposide, Ara-C and melphalan (BEAM) for all NHL and those HL patients who are unable to receive CBV

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

Approved in United States as Carmustine for:

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

Approved in European Union as Carmustine for:

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

Approved in Canada as Carmustine for:

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

Who Is Running the Clinical Trial?

Masonic Cancer Center, University of Minnesota

Lead Sponsor

Trials

285

Recruited

15,700+

Findings from Research

In a study involving 77 patients with Hodgkin's disease and non-Hodgkin's lymphoma, high-dose etoposide combined with either fractionated total body irradiation (TBI) or carmustine before autologous bone marrow transplantation showed promising results, with a 1-year survival rate of 85% for TBI patients and 79% for carmustine patients.

Despite the effectiveness, there was an 8% rate of toxic deaths, all occurring in the carmustine group, highlighting a safety concern associated with this treatment regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Stanford experience with high-dose etoposide cytoreductive regimens and autologous bone marrow transplantation in Hodgkin's disease and non-Hodgkin's lymphoma: preliminary data. Horning, SJ., Chao, NJ., Negrin, RS., et al.[2020]

Patients with hematological malignancies experienced slower recovery of neutrophils and platelets after autologous peripheral blood stem cell transplantation compared to those with solid tumors, indicating a higher risk of complications.

Hematological malignancy patients required more red blood cell and platelet transfusions, had longer hospital stays, and experienced more severe mucositis, highlighting the increased transplant-related complications in this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences in transplant-related complications between hematologic malignancies and solid tumors receiving high-dose chemotherapy and autologous peripheral blood stem cell transplantation. Martino, M., Morabito, F., Console, G., et al.[2022]

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]

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 involving 10 patients with relapsed or refractory Hodgkin and non-Hodgkin lymphoma, substituting carmustine with cisplatin and dexamethasone in the BEAM conditioning regimen resulted in a 70% complete response rate after autologous stem cell transplant.

The overall survival rate at 12 months was 100% for Hodgkin lymphoma patients and 63% for non-Hodgkin lymphoma patients, suggesting that this alternative regimen is effective and may offer a more accessible treatment option in developing countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BEAM-Modified Conditioning Therapy with Cisplatin+Dexamethasone Instead of Carmustine Prior to Autologous Hematopoietic Stem Cell Transplantation (HSCT) in Patients with Hodgkin and Non-Hodgkin Lymphoma. Ron-Magaña, AL., Fernandez-Vargas, OE., Barrera-Chairez, E., et al.[2020]

In a study of 102 patients with relapsed lymphoma, the BEAM conditioning regimen before autologous hematopoietic stem cell transplantation (AHSCT) showed significantly better progression-free survival (PFS) at 55% compared to 30.6% for the mitoxantrone-melphalan regimen, indicating its superior efficacy.

Overall survival rates were similar for both regimens (86% for BEAM vs. 84% for mitoxantrone-melphalan), suggesting that while BEAM may improve PFS, both treatment options are viable for patients undergoing AHSCT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Retrospective Comparison of Mitoxantrone-Melphalan and BEAM Conditioning Regimens Before Autologous Hematopoietic Stem Cell Transplantation in Relapsed/Refractory Lymphoma Patients. Halacoglu, A., Serefhanoglu, S.[2023]

EVOMELA, a new formulation of melphalan that is free from propylene glycol, has been shown to be safe and effective for high-dose conditioning in autologous stem cell transplantation for multiple myeloma, with a 100% overall response rate in a study of 61 patients.

The study reported low incidences of severe side effects, such as grade 3 mucositis (10%) and stomatitis (5%), indicating that EVOMELA has an acceptable safety profile compared to traditional formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase IIb, Multicenter, Open-Label, Safety, and Efficacy Study of High-Dose, Propylene Glycol-Free Melphalan Hydrochloride for Injection (EVOMELA) for Myeloablative Conditioning in Multiple Myeloma Patients Undergoing Autologous Transplantation. Hari, P., Aljitawi, OS., Arce-Lara, C., et al.[2017]

In a study involving 29 patients treated with a high-dose combination of cyclophosphamide, cisplatin, and carmustine (BCNU), the maximum tolerated doses were determined, revealing significant dose-related toxicity, including multiple organ damage.

The treatment led to objective tumor regression in 21 out of 25 evaluable cases, indicating that this combination therapy can be effective in treating certain cancers despite the risks of severe side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose combination alkylating agents with autologous bone marrow support: a Phase 1 trial. Peters, WP., Eder, JP., Henner, WD., et al.[2017]

The study established the maximum-tolerated doses (MTD) for the chemotherapy combination BACE, which includes carmustine, Ara C, cyclophosphamide, and etoposide, with carmustine at 700 mg/m2 being the highest safe dose.

Out of 37 patients treated, 75% achieved complete or partial responses, and no toxic deaths occurred among those treated at the MTD, indicating that the regimen can be effective and relatively safe when dosed appropriately.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carmustine, Ara C, cyclophosphamide and etoposide with autologous bone marrow transplantation in relapsed or refractory lymphoma: a dose-finding study. Snyder, MJ., Johnson, DB., Daly, MB., et al.[2013]

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]

High-dose melphalan is the preferred chemotherapy for autologous stem cell transplantation in multiple myeloma patients, supported by earlier randomized trials.

Alternative treatment regimens involving different combinations of drugs and radiation have not shown better results than high-dose melphalan alone, according to multiple published studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple myeloma preparative regimens for high-dose therapy and autologous transplantation: what's new? Aljitawi, OS., McGuirk, JP.[2013]

In a study of 108 relapsed/refractory lymphoma patients, both TECAM and BEAM conditioning regimens showed similar efficacy, with 2-year progression-free survival rates of 55.7% and 52.9%, respectively, indicating that TECAM is a viable option before autologous stem cell transplant.

While the overall survival rate was slightly lower for the TECAM group (55.9%) compared to the BEAM group (67%), the differences were not statistically significant, suggesting comparable safety and effectiveness between the two regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Retrospective Comparison of TECAM and BEAM Conditioning Regimens Before Autologous Hematopoietic Stem Cell Transplant in Lymphoma Patients: Efficacy and Toxicity. Patir, P., Soyer, N., Durusoy, IR., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

The Stanford experience with high-dose etoposide cytoreductive regimens and autologous bone marrow transplantation in Hodgkin's disease and non-Hodgkin's lymphoma: preliminary data. [2020]

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

Differences in transplant-related complications between hematologic malignancies and solid tumors receiving high-dose chemotherapy and autologous peripheral blood stem cell transplantation. [2022]

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

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

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

BEAM-Modified Conditioning Therapy with Cisplatin+Dexamethasone Instead of Carmustine Prior to Autologous Hematopoietic Stem Cell Transplantation (HSCT) in Patients with Hodgkin and Non-Hodgkin Lymphoma. [2020]

6. India pubmed.ncbi.nlm.nih.gov

A Retrospective Comparison of Mitoxantrone-Melphalan and BEAM Conditioning Regimens Before Autologous Hematopoietic Stem Cell Transplantation in Relapsed/Refractory Lymphoma Patients. [2023]

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

A Phase IIb, Multicenter, Open-Label, Safety, and Efficacy Study of High-Dose, Propylene Glycol-Free Melphalan Hydrochloride for Injection (EVOMELA) for Myeloablative Conditioning in Multiple Myeloma Patients Undergoing Autologous Transplantation. [2017]

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

High-dose combination alkylating agents with autologous bone marrow support: a Phase 1 trial. [2017]

9. England pubmed.ncbi.nlm.nih.gov

Carmustine, Ara C, cyclophosphamide and etoposide with autologous bone marrow transplantation in relapsed or refractory lymphoma: a dose-finding study. [2013]

10. 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]

11. England pubmed.ncbi.nlm.nih.gov

Multiple myeloma preparative regimens for high-dose therapy and autologous transplantation: what's new? [2013]

12. Turkey pubmed.ncbi.nlm.nih.gov

A Retrospective Comparison of TECAM and BEAM Conditioning Regimens Before Autologous Hematopoietic Stem Cell Transplant in Lymphoma Patients: Efficacy and Toxicity. [2019]