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

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different doses of stem cells affect recovery in individuals with non-Hodgkin's lymphoma, a type of blood cancer. Participants will undergo high-dose chemotherapy, including drugs like Carmustine, Cytarabine, Etoposide, and Melphalan, followed by an autologous stem cell transplant, which uses their own stem cells to rebuild the immune system. The trial will compare two groups receiving different stem cell doses to determine which is more effective. Individuals who have experienced a return or worsening of non-Hodgkin's lymphoma after chemotherapy and have shown some improvement with another round of treatment might be suitable for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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.

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

Research has shown that using a patient's own stem cells for treatment, known as autologous stem cell transplantation (ASCT), is generally safe for treating non-Hodgkin's lymphoma. In one study, two years after treatment, 66% of patients were still alive, and 58% had no worsening of their disease, indicating that the treatment is usually well-tolerated. Another study found a low risk of dying from the treatment itself, especially as medical procedures have improved over time.

The chemotherapy drugs used in this treatment—Carmustine, Cytarabine, Etoposide, and Melphalan—are commonly used in cancer care. These drugs can cause side effects like nausea, low blood cell counts, and hair loss, but supportive care often manages these effects. Overall, the combination of ASCT and these chemotherapy drugs has proven tolerable for most patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the high-dose therapy and autologous stem cell transplant for Non-Hodgkin's Lymphoma because it offers a potentially more effective way to treat this condition compared to standard chemotherapy and immunotherapy options. Unlike traditional treatments, this approach uses the patient's own stem cells to rebuild the immune system after high-dose chemotherapy, potentially reducing the risk of relapse. The combination of high-dose chemotherapy with drugs like Carmustine, Cytarabine, Etoposide, and Melphalan aims to aggressively target cancer cells, which might lead to better outcomes for patients. This personalized approach could offer hope for those who haven't responded well to conventional treatments.

What evidence suggests that this trial's treatments could be effective for Non-Hodgkin's Lymphoma?

Research has shown that using a patient's own stem cells for treatment, known as autologous stem cell transplantation (ASCT), can be a promising option for non-Hodgkin's lymphoma. One study found that patients who received high-dose therapy followed by ASCT had a 71% survival rate after three years, compared to just 11% for those who did not receive this treatment. Another study indicated that five years after ASCT, about 48% of patients were still alive, suggesting its potential long-term benefits. ASCT works particularly well for patients whose disease responds to chemotherapy. Overall, ASCT is considered a curative option for many people with non-Hodgkin's lymphoma.

In this trial, participants will receive different dosages of CD34+ stem cells/kg as part of the ASCT process. One group will receive 6-8 x 10^6 CD34+ stem cells/kg, while another group will receive 3-4 x 10^6 CD34+ stem cells/kg. ^{4 6 7 8 9}

Who Is on the Research Team?

Sergio Giralt, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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 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.

pmc.ncbi.nlm.nih.gov

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

A review of autologous stem cell transplantation in ...

The estimated 3-year OS was 71% for patients who underwent HDT/ASCT compared to 11% for patients who did not. Corradini and colleagues (2014) studied the role ...

2.

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.

3.

ascopubs.org

ascopubs.org/doi/10.1200/GO.21.00383

Long-Term Outcomes and Safety Trends of Autologous ...

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 ...

4.

ashpublications.org

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

Autologous stem cell transplantation for relapsed/refractory ...

Our results indicate that ASCT is a curative option for patients with chemosensitive disease especially in CR after salvage.

5.

annalsofoncology.org

annalsofoncology.org/article/S0923-7534(20)38288-0/fulltext

Autologous stem cell transplantation (ASCT) is safe and ...

The specific survival was similar between the 2 groups, 65% for the young pts group vs 72% for the older (p = 0.63) 3 years after ASCT. Conclusions: High-dose ...

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.

ascopubs.org

ascopubs.org/doi/abs/10.1200/GO.21.00383

Long-Term Outcomes and Safety Trends of Autologous ...

Safety and efficacy of autologous stem cell transplantation ... Outcomes of Autologous Stem-Cell Transplantation for Non-Hodgkin's Lymphoma.

8.

asco.org

asco.org/abstracts-presentations/ABSTRACT182277

Safety and efficacy of autologous stem cell transplantation ...

Two-year progression-free survival and overall survival were 58% (95%CI, 48-67%) and 66% (95%CI, 55-74%), respectively. The leading cause of treatment failure ...

9.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/35561291/

A Report From A Tertiary Care Center in India

At a median follow-up of 57.6 months, the 5-year event-free survival (EFS) and overall survival (OS) were 43.5% and 47.6%, respectively, for all patients.