Radioimmunotherapy + CAR T-cell Therapy for Acute Lymphoblastic Leukemia and Non-Hodgkin's Lymphoma

Recruiting at 6 trial locations

Overseen By Neeta Pandit-Taskar, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: T-cell suppressive therapy

Disqualifiers: HIV, Hepatitis B/C, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments for specific blood cancers, namely acute lymphoblastic leukemia and non-Hodgkin's lymphoma. The aim is to determine a safe dose of a radioactive drug, 131-I apamistamab, when administered before CAR T-cell therapy. This therapy involves modifying a patient’s T-cells to enhance their ability to fight cancer. The trial targets patients whose cancer has returned or not responded to previous treatments and who still have detectable cancer despite therapy. Participants should have B-cell acute lymphoblastic leukemia or diffuse large B-cell lymphoma that has either not responded to prior therapies or has recurred after initial treatment. As an Early Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the chance 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 whether you need to stop taking your current medications. It's best to discuss your specific medications with the trial team to get a clear answer.

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

Research has shown that 131-I apamistamab has been tested in other situations and is generally well-tolerated. In one study, patients treated with 131-I apamistamab demonstrated a good survival rate, with over 90% of those who had a lasting complete response still alive after one year. This suggests the treatment is relatively safe, although specific side effects were not detailed in the information provided.

CAR T-cell therapy is more familiar to doctors because the FDA has already approved it for other conditions. However, it can have significant side effects. A common side effect is Cytokine Release Syndrome (CRS), affecting about 82% of patients. CRS can cause symptoms like fever, tiredness, and nausea, but proper care usually manages it.

Both treatments have shown promise, but they can come with side effects. Always consult a healthcare provider to understand the risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of radioimmunotherapy and CAR T-cell therapy for treating acute lymphoblastic leukemia and non-Hodgkin's lymphoma because these treatments offer a novel approach compared to standard therapies like chemotherapy and monoclonal antibodies. Unlike traditional treatments, 131-I Apamistamab targets cancer cells with precision by delivering radiation directly to the cancerous cells, minimizing damage to healthy tissues. CAR T-cell therapy, on the other hand, involves reprogramming a patient's own immune cells to attack cancer, offering a highly personalized treatment option. Together, these therapies have the potential to improve outcomes for patients with difficult-to-treat forms of these cancers by precisely targeting and destroying cancer cells.

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

Research has shown that 131-I Apamistamab, one of the treatments studied in this trial, yields promising results. In one study, patients with a strong complete response to this treatment had high survival rates, with 92.3% alive after one year. It has also improved outcomes for high-risk patients.

CAR T-cell therapy, the other treatment under investigation, has a strong history of success, particularly in children and young adults with acute lymphoblastic leukemia. Studies report an overall remission rate of 81%. Many patients achieve long-term remission, even those with minimal disease before treatment.

Both treatments are powerful individually, and this trial will explore the potential effectiveness of combining them for conditions like acute lymphoblastic leukemia and non-Hodgkin's lymphoma. ^{2 3 4 6 7}

Who Is on the Research Team?

Mark B Geyer, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults with relapsed or refractory B-cell acute lymphoblastic leukemia or diffuse large B-cell lymphoma, who have tried and not responded to previous treatments. They must have a certain level of organ function, no severe heart conditions, and cannot be pregnant. Those with active infections or other serious health issues are excluded.

Inclusion Criteria

I have B-cell acute lymphoblastic leukemia or chronic myeloid leukemia in blast crisis.

Absolute neutrophil count ≥0.5k/µL,

I had treatment for my cancer relapse but don't need a recent test to join the study for leukapheresis. I need proof of cancer for the next treatment phase.

Exclusion Criteria

I have significant difficulty in performing daily activities.

I have a severe heart condition with very low heart pump function.

Have current or prior positive test results for human immunodeficiency virus (HIV) or hepatitis B (HBV) or C (HCV), with the following exceptions:

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive 131-I apamistamab to determine the maximum tolerated dose

1 week

Treatment

Participants receive CD19-targeted CAR T-cell therapy following 131-I apamistamab

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 131-I Apamistamab
• CAR T-cell

Trial Overview The trial is testing the combination of a radioactive antibody called 131-I apamistamab followed by CAR T-cell therapy in patients with specific types of blood cancer. The goal is to find the highest dose that patients can tolerate without too many side effects.

How Is the Trial Designed?

Group I: B-Cell Acute Lymphoblastic Leukemia/Diffuse Large B-Cell Lym Experimental Treatment 2 Interventions

Participants will have relapsed or refractory B-Cell Acute Lymphoblastic Leukemia or Diffused Large B-Cell Lymphoma

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Actinium Pharmaceuticals

Industry Sponsor

Trials

8

Recruited

290+

Published Research Related to This Trial

T-cell-engaging immunotherapies, like blinatumomab and CAR T-cell therapy, have shown remarkable remission rates in patients with relapsed or refractory acute lymphoblastic leukemia (ALL), highlighting their efficacy in treating this challenging condition.

Cytokine release syndrome (CRS) is a significant side effect of these therapies, characterized by symptoms like fever and malaise, and can lead to severe complications. Management strategies include using tocilizumab for severe CRS and preventive measures like corticosteroid premedication during blinatumomab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine release syndrome with novel therapeutics for acute lymphoblastic leukemia. Frey, NV., Porter, DL.[2022]

Immunotherapy, including monoclonal antibodies and CAR T cells, has shown superior efficacy and safety compared to traditional chemotherapy in treating relapsed/refractory acute lymphoblastic leukemia (ALL), particularly in adults with high-risk disease.

Ongoing trials are exploring the combination of monoclonal antibodies with chemotherapy and their potential use in earlier treatment stages, which may lead to better outcomes than current standard care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging role of immunotherapy in precursor B-cell acute lymphoblastic leukemia. Valecha, GK., Ibrahim, U., Ghanem, S., et al.[2018]

T-cell engaging therapies like blinatumomab and CAR T cells have significantly improved treatment outcomes for patients with relapsed and refractory acute lymphoblastic leukemia (ALL), but they can also cause cytokine release syndrome (CRS), which leads to serious side effects such as fever and hemodynamic instability.

Tocilizumab effectively manages severe CRS without harming T cells, while blinatumomab's CRS management focuses on prevention through strategies like disease cytoreduction and corticosteroid premedication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine release syndrome: Who is at risk and how to treat. Frey, N.[2022]

In a phase 1 trial of 53 adults with relapsed B-cell acute lymphoblastic leukemia, 83% achieved complete remission after receiving CD19-specific CAR T cells, indicating high initial efficacy.

Patients with a low disease burden before treatment experienced significantly longer overall survival (20.1 months) and fewer severe side effects, such as cytokine release syndrome, compared to those with a higher disease burden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia. Park, JH., Rivière, I., Gonen, M., et al.[2023]

In a phase I trial involving 12 younger patients with relapsed or refractory B-cell acute lymphoblastic leukemia, the use of chimeric antigen receptor T cells targeting CD19 and CD22 showed manageable toxicity levels.

Out of the 12 patients, 5 achieved complete responses, indicating promising efficacy of this treatment approach in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting CD19-CD22 Aids Younger Patients with ALL. [2021]

The CD22/CD19 dual-targeting CAR-T-cell therapy showed a remarkable overall response rate of 97% and a complete remission rate of 93% in patients with relapsed/refractory acute lymphoblastic leukemia (ALL), based on a meta-analysis of 14 studies involving 405 patients.

For non-Hodgkin lymphoma (NHL), the therapy resulted in an overall response rate of 85% and a complete remission rate of 57%, with manageable side effects such as cytokine release syndrome occurring in 86% of patients, indicating both efficacy and tolerability of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of CD22 and CD19 dual-targeting chimeric antigen receptor T-cell therapy in patients with relapsed or refractory B-cell malignancies: A meta-analysis. Nguyen, TT., Thanh Nhu, N., Chen, CL., et al.[2023]

In a phase 1 trial involving 15 pediatric and young adult patients with relapsed or refractory B-ALL, the dual-targeting CAR T-cell therapy AUTO3 demonstrated a favorable safety profile with no severe toxicities reported and an impressive remission rate of 86% one month post-treatment.

Despite the high initial remission rate, the one-year overall survival rate was 60% and event-free survival rate was 32%, indicating that improvements in the persistence of AUTO3 CAR T-cells are necessary to enhance long-term outcomes and prevent relapses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T cells with dual targeting of CD19 and CD22 in pediatric and young adult patients with relapsed or refractory B cell acute lymphoblastic leukemia: a phase 1 trial. Cordoba, S., Onuoha, S., Thomas, S., et al.[2022]

T-cell acute lymphoblastic leukemia (T-ALL) remains difficult to treat, especially in relapsed or resistant cases, due to limited novel therapeutic options and challenges like shared surface targets between normal and cancerous T-cells.

Recent advancements in immunotherapy, including monoclonal antibodies, bispecific T-cell engagers (BTCEs), and CAR T-cells, show promising results and are progressing through clinical trials, offering hope for improved treatment strategies for T-ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The emerging scenario of immunotherapy for T-cell Acute Lymphoblastic Leukemia: advances, challenges and future perspectives. Caracciolo, D., Mancuso, A., Polerà, N., et al.[2023]

CAR-modified T cell therapy targeting the CD19 antigen has shown remarkable efficacy in treating relapsed/refractory acute lymphoblastic leukemia, achieving complete remission rates as high as 90%.

While this therapy is highly effective, it also leads to significant T-cell proliferation, which can cause cytokine release syndrome, highlighting the need for improved management strategies for this toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cell therapy for ALL. Maude, SL., Shpall, EJ., Grupp, SA.[2020]

In a phase II trial involving 225 patients aged 20 and under, coadministration of CD19- and CD22-CAR T cells resulted in a remarkable 99% complete remission rate for those with refractory B-acute lymphoblastic leukemia, with a 12-month event-free survival (EFS) rate of 73.5%.

While the treatment was effective, it was associated with significant side effects, including cytokine release syndrome in 88% of patients and CAR T-cell neurotoxicity in 20.9%, leading to three deaths, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Coadministration of CD19- and CD22-Directed Chimeric Antigen Receptor T-Cell Therapy in Childhood B-Cell Acute Lymphoblastic Leukemia: A Single-Arm, Multicenter, Phase II Trial. Wang, T., Tang, Y., Cai, J., et al.[2023]

Immunotherapeutic strategies targeting specific surface antigens on acute lymphoblastic leukemia (ALL) cells are being explored as novel treatment options to improve poor outcomes in adult patients.

The review highlights four major classes of antibody therapies, including naked antibodies, immunoconjugates, BiTE therapy, and CAR T-cell therapy, and discusses their potential integration into current treatment protocols for ALL based on preclinical and clinical data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future of Therapy in Acute Lymphoblastic Leukemia (ALL)--Potential Role of Immune-Based Therapies. Kebriaei, P., Poon, ML.[2018]

An 11-year-old girl with relapsed acute B lymphoblastic leukemia (B-ALL) was treated with fourth generation CD19 CAR-T therapy, which was found to be effective and safe, resulting in a negative minimal residual disease after treatment.

Despite initial success and 10 months of disease-free survival, the patient ultimately relapsed due to increasing TEL-AML1 gene copies, highlighting the need for ongoing monitoring and potential further interventions in CAR-T therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chimeric antigen receptors T cells in treatment of a relapsed pediatric acute lymphoblastic leukemia, relapse after allogenetic hematopoietic stem cell transplantation: case report and review of literature review]. Zuo, Y., Wang, J., Lu, A., et al.[2020]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.02018

Randomized Phase III SIERRA Trial of 131 I-Apamistamab ... Of 13 patients who achieved a dCR with 131I-apamistamab, 92.3% were alive at 1 year, 69.2% were alive at 2 years, and the median OS was not ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04512716

NCT04512716 | Iomab-ACT: A Pilot Study of 131-I ... This is a pilot study; patients will receive 131-I apamistamab prior to CAR T-cell infusion in order to determine the maximum tolerated dose of 131-I ...

3. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/2159/502596/131I-Apamistamab-Effectively-Achieved-Durable

131 I-Apamistamab Effectively Achieved Durable Responses ... I-apamistamab was effective in achieving durable responses in R/R AML pts irrespective of the presence of multiple risk factors and successfully ...

4. astctjournal.org astctjournal.org/article/S2666-6367(23)01824-9/fulltext

131I-Apamistamab Improves Outcomes in Patients 65 ... Iomab-B was effective in improving outcomes despite advancing age and presence of these very high-risk features.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39298738/

Randomized Phase III SIERRA Trial of 131 I-Apamistamab ... The 131 I-apamistamab-led regimen was associated with a higher dCR rate than conventional care in older patients with RR AML.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0928125824003103

Outcomes and radiation safety of Iomab-B (131I ... The primary endpoint of durable CR (dCR) at 6 months strongly favored Iomab-B with 22% dCR vs. 0% for CC (p < 0.0001). Iomab-B followed by HCT was well ...

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-01361

A Study of 131-I Apamistamab and CAR T-cell Therapy in ... This phase I trial is to find out the best dose, possible benefits and/or side effects of 131-I apamistamab given before CAR T-cell therapy in treating ...