High-Dose Therapy and Autologous Stem Cell Transplant for Non-Hodgkin's Lymphoma

Recruiting at 15 trial locations

Overseen By Craig Sauter, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: HIV, Prior stem cell 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

Duration: Hospital admission

59 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing how different amounts of a specific type of stem cell affect the outcomes of patients who receive their own stem cells back after treatment. It targets patients undergoing stem cell transplants. The treatment involves collecting, freezing, and re-infusing different amounts of these stem cells to see which dose works best. This method has been used in various clinical trials for treating multiple diseases, including multiple sclerosis and multiple myeloma.

Do I need to stop my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the treatment High-Dose Therapy and Autologous Stem Cell Transplant for Non-Hodgkin's Lymphoma?

Research shows that the BEAM regimen, which includes carmustine, etoposide, cytarabine, and melphalan, is frequently used and effective for patients with lymphoma undergoing autologous stem cell transplantation. Studies indicate that this regimen is effective in treating aggressive forms of lymphoma, providing promising results in patients with partially responding or relapsed conditions. ^{1 2 3 4 5}

Is high-dose therapy and autologous stem cell transplant safe for humans?

High-dose therapy and autologous stem cell transplant can cause severe side effects like infections, fever, and mouth sores, especially in older patients. However, there were no treatment-related deaths in a study, and most patients recovered their blood cell counts within a few weeks. ^{1 2 5 6 7}

How does the high-dose therapy and autologous stem cell transplant treatment for non-Hodgkin's lymphoma differ from other treatments?

This treatment uses a combination of high-dose chemotherapy drugs, including carmustine, cytarabine, etoposide, and melphalan, followed by autologous stem cell transplantation, which is a standard approach for relapsed or refractory non-Hodgkin's lymphoma. It is unique because it combines these specific drugs to prepare the body for stem cell rescue, aiming to improve outcomes by using high-dose chemotherapy to eliminate cancer cells before replenishing the body's blood-forming cells. ^{2 8 9 10 11}

Research Team

Sergio Giralt, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults over 18 with relapsed or refractory DLBCL who've had one prior anthracycline-based chemotherapy can join. They should be fairly fit (KPS ≥ 70), have decent kidney function, and not too high bilirubin levels in the blood. Women and men must use birth control, and they shouldn't have HIV or other conditions that would interfere with stem cell procedures.

Inclusion Criteria

My total bilirubin is over 2.0 mg/dL, but my direct bilirubin is under 2.0 mg/dL.

I am eligible for a treatment involving high-dose therapy and my own stem cells.

I've had a good response to one round of chemotherapy without prior high-dose therapy or stem cell transplant.

Exclusion Criteria

My doctor thinks my health conditions won't allow for a specific stem cell treatment.

I have received targeted radiation therapy as part of my salvage treatment.

I am HIV positive.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Stem Cell Mobilization

Patients are CD34+ stem cell mobilized with plerixafor to achieve >6 x10^6 CD34+ cells/kg

Varies

Treatment

Patients receive high-dose therapy and autologous stem cell transplantation (ASCT) with randomized CD34+ cell dose

Hospital admission

Follow-up

Participants are monitored for disease progression and overall survival, including lymphocyte subset recovery

15 days for initial assessment, long-term for progression-free survival

Treatment Details

Interventions

• Autologous Stem Cell Transplantation
• Carmustine
• Cytarabine
• Etoposide
• Leukapheresis
• Melphalan
• Plerixafor

Trial Overview The trial is examining how different doses of CD34+ stem cells affect recovery after a high-dose therapy followed by an autologous stem cell transplant in patients with certain types of B-cell lymphoma.

Participant Groups

Group I: 6-8 x10^6 CD34+ stem cells/kg Experimental Treatment 4 Interventions

Patients will receive standard supportive measures (including: growth factor support post-HDT/ASCT, antimicrobial prophylaxis, red blood cell and platelet transfusion and treatment for neutropenic fever) as per institutional guideline practices.

Group II: 3-4 x 10^6 CD34+ stem cells/kg Active Control 4 Interventions

Patients will receive standard supportive measures (including: growth factor support post-HDT/ASCT, antimicrobial prophylaxis, red blood cell and platelet transfusion and treatment for neutropenic fever) as per institutional guideline practices.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Endeavor Health

Collaborator

Trials

135

Recruited

742,000+

The Cleveland Clinic

Collaborator

Trials

1,072

Recruited

1,377,000+

Medical College of Wisconsin

Collaborator

Trials

645

Recruited

1,180,000+

NorthShore University HealthSystem

Collaborator

Trials

134

Recruited

740,000+

Columbia University

Collaborator

Trials

1,529

Recruited

2,832,000+

University of Rochester

Collaborator

Trials

883

Recruited

555,000+

University of Nebraska

Collaborator

Trials

563

Recruited

1,147,000+

Sanofi

Industry Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

University Hospitals Seidman Cancer Center

Collaborator

Trials

5

Recruited

1,100+

Findings from Research

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 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]

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]

References

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

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

2. 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]

3. 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]

4. 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]

5. Japan pubmed.ncbi.nlm.nih.gov

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

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

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

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

Phase II Study of Propylene Glycol-Free Melphalan Combined with Carmustine, Etoposide, and Cytarabine for Myeloablative Conditioning in Lymphoma Patients Undergoing Autologous Stem Cell Transplantation. [2018]

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

Autotransplantation for relapsed or refractory non-Hodgkin's lymphoma (NHL): long-term follow-up and analysis of prognostic factors. [2006]

9. Italy pubmed.ncbi.nlm.nih.gov

High-dose thiotepa, etoposide and carboplatin as conditioning regimen for autologous stem cell transplantation in patients with high-risk non-Hodgkin lymphoma. [2022]

10. 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]

11. 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]