Autologous Stem Cell Transplant + CAR T-Cell Therapy for B-Cell Lymphoma

Not currently recruiting at 6 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Burkitt lymphoma, HIV, active hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for aggressive B-cell non-Hodgkin lymphoma, a cancer affecting the immune system. Researchers aim to determine the safety of using a patient's own T cells (a type of immune cell) after chemotherapy and a stem cell transplant. The trial administers varying doses of these modified T cells, known as 19-28z T cells, to identify the safest amount. Individuals with relapsed or hard-to-treat B-cell lymphoma, who have specific treatment histories and meet certain health criteria, may qualify. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

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

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

Research has shown that a type of CAR T-cell therapy, called 19-28z, holds promise for treating B-cell lymphomas. In one study, 12 out of 13 patients with this cancer type experienced positive results. Eight of these patients had complete responses, meaning their cancer signs disappeared.

Patients have tolerated the treatment well, with few long-term side effects reported. Another study found that these CAR T-cells can keep the cancer away for an extended period.

Although this treatment remains in the early testing stages, these initial results suggest it is both promising and relatively safe for many patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for B-cell lymphoma, which typically involve chemotherapy and radiation, the combination of Autologous Stem Cell Transplant and CAR T-cell therapy offers a targeted approach. Researchers are excited because this therapy harnesses the patient's own immune system to fight cancer, potentially reducing the risk of relapse. CAR T-cell therapy involves genetically modifying T-cells to better identify and destroy cancer cells, which is a novel mechanism compared to traditional methods. This treatment aims to improve outcomes for patients with aggressive B-cell lymphoma, particularly those who have not responded to other therapies.

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

Research has shown that CAR T-cell therapy, a treatment under study in this trial, holds promise for treating B-cell lymphomas. In one study, this therapy helped 12 out of 13 patients, with eight showing no detectable cancer afterward. CAR T-cells work by modifying a patient’s own T-cells to better locate and attack cancer cells. Another study found that this therapy can maintain cancer remission for an extended period. Overall, these findings suggest that CAR T-cell therapy could be a strong option for treating aggressive B-cell lymphomas. ^{1 2 3 6 7}

Who Is on the Research Team?

Mark Geyer, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with aggressive B-cell non-Hodgkin lymphoma who've relapsed or are not responding to treatment. They should have a life expectancy of more than 3 months, good kidney and liver function, no severe heart or lung issues, and no other cancers that could interfere with the study. Those previously treated with bone marrow or stem cell transplants, or those with uncontrolled infections including HIV and hepatitis B/C can't participate.

Inclusion Criteria

- Life expectancy of > 3 months.

- Bilirubin < 2.0 mg/100 ml, AST and ALT < 3x the upper limit of normal, PT and PTT < 2x normal outside the setting of stable chronic anticoagulation therapy

My heart is functioning well, with an LVEF greater than 40%.

Exclusion Criteria

- Patients with HIV, active hepatitis B, or hepatitis C infection.

I have had cancer before, but it doesn't affect my current study participation.

I have not had a bone marrow or stem cell transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

High Dose Chemotherapy and ASCT

Participants receive high-dose chemotherapy followed by autologous stem cell transplantation

4-6 weeks

CAR T-Cell Infusion

Infusion of CAR modified T-cells to determine the maximum tolerated dose

1-2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• 19-28z T CELLS
• Autologous Stem Cell Transplantation
• Carmustine
• Cytarabine
• Etoposide
• Melphalan

Trial Overview The trial tests high-dose chemotherapy followed by returning patients' own stem cells (ASCT) and then infusing their T-cells modified to target CD19+ B-cells (CAR-T therapy). It aims to see if this combination is safe for treating refractory/relapsed aggressive B-cell non-Hodgkin lymphoma.

How Is the Trial Designed?

Group I: HIGH DOSE CHEMOTHERAPY AND ASCT Experimental Treatment 7 Interventions

This is a phase 1 dose escalation study designed to determine the maximum tolerated dose (MTD) of CAR modified T cells in patients with relapsed and refractory aggressive B-NHL. Three dose levels (5 x 106 19-28z T cells/kg, 1 x 107 19-28z T cells/kg, and 2 x 107 19-28z T cells/kg) are considered for the MTD.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6466472/

CAR T-cell therapy for B-cell lymphomas: clinical trial results ... Single-center and multicenter clinical trials with anti-CD19 CAR T-cell therapy have shown great activity and long-term remissions in poor-risk diffuse large B ...

2. researchgate.net researchgate.net/publication/332585983_Phase_I_trial_of_19-28z_chimeric_antigen_receptor_modified_T_cells_19-28z_CAR-T_post-high_dose_therapy_and_autologous_stem_cell_transplant_HDT-ASCT_for_relapsed_and_refractory_relref_aggressive_B-cell

Phase I trial of 19-28z chimeric antigen receptor modified T ... In an adult series of patients with B-cell lymphoma, responses to CD19 CAR T-cells were seen in 12 of 13 patients including eight complete responses and four ...

3. ashpublications.org ashpublications.org/bloodadvances/article/9/7/1644/535452/Allogeneic-off-the-shelf-CAR-T-cell-therapy-for

Allogeneic off-the-shelf CAR T-cell therapy for relapsed or ... OS at 36 months was 92% for patients treated with third-party T cells (n = 12) and 25% for patients treated with their allo-HCT donors' T cells ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10100620/

Long-term outcomes following CAR T cell therapy The data demonstrate that CD19-targeted CAR T cells can induce prolonged remissions in patients with B cell malignancies, often with minimal long-term ...

5. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.00849/full

CAR T-Cell Therapy for B-Cell non-Hodgkin Lymphoma ... Chimeric antigen receptor-modified (CAR) T cells targeting CD19 have revolutionized the treatment of relapsed or refractory aggressive B-cell lymphomas, ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0006497119696163

a Phase I Trial of High Dose Therapy and Autologous Stem ... This is the first report of 19-28z CAR-T cells in conjunction with consolidative HDT-ASCT for poor-risk rel/ref aggressive B-NHL.

7. ashpublications.org ashpublications.org/bloodadvances/article/9/20/5362/546293/Survival-after-anti-CD19-CAR-T-cell-therapy-for-B

Survival after anti-CD19 CAR T-cell therapy for B-cell non ... Previous publication of 5-year follow-up data of axi-cel for LBCL demonstrated an estimated 5-year event-free survival (EFS) of 30.3% and overall survival (OS) ...