Immunotherapy for Infant Leukemia

Recruiting at 25 trial locations

Overseen By Tanja A Gruber, MD, PhD

Age: < 18

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Tanja Andrea Gruber

Disqualifiers: Prior therapy, Down syndrome, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

90 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to improve upon the TINI study treatment. The study will test the ability of a type of immunotherapy called blinatumomab to clear persistent leukemia. Blinatumomab targets CD19 which is located on the leukemia cells outer membrane.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it does mention that only limited prior therapy is allowed. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Blinatumomab (Blincyto) for treating infant leukemia?

Research shows that Blinatumomab is effective in treating certain types of leukemia by helping the body get rid of cancer cells, especially in cases where other treatments have not worked well. In infants with leukemia, it has shown promise in achieving remission before further treatment, with some patients experiencing long-term survival. ^{1 2 3 4 5}

Is blinatumomab (Blincyto) safe for use in humans?

Blinatumomab has been used in children and adults with certain types of leukemia, but it can cause serious side effects like cytokine release syndrome (a severe immune reaction) and neurological problems (such as seizures). Other common side effects include fever, headache, and nausea. ^{2 4 6 7 8}

How is the drug blinatumomab different from other treatments for infant leukemia?

Blinatumomab is unique because it is a bispecific T-cell engager, which means it helps the body's immune cells target and destroy cancer cells. This drug is used for certain types of leukemia that have relapsed or are hard to treat, and it works differently from traditional chemotherapy by directly engaging the immune system. ^{8 9 10 11 12}

Research Team

Tanja A Gruber, MD, PhD

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for infants up to 1 year old with a new diagnosis of CD19 positive acute lymphoblastic leukemia or related conditions, with limited prior treatment. They must have more than 25% leukemia cells in their bone marrow and can have some previous short-term treatments like hydroxyurea or glucocorticoids.

Inclusion Criteria

I've had minimal prior cancer treatment, following the specific limits provided.

Written informed consent following Institutional Review Board, NCI, FDA, and OHRP Guidelines

I have a specific type of leukemia that tests positive for CD19.

Exclusion Criteria

Inability or unwillingness of legal guardian/representative to give written informed consent

Patients with Down syndrome

I have received treatments not listed in the trial's accepted therapies.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Remission Induction

Participants receive initial treatment to induce remission using a combination of chemotherapy and immunotherapy

8 weeks

Induction Intensification

Participants undergo intensified treatment to clear persistent leukemia, including the use of blinatumomab

8 weeks

Consolidation I

Participants receive treatment to consolidate remission and prevent relapse

12 weeks

Reinduction Block I

Participants undergo reinduction therapy to further reduce leukemia cells

6 weeks

Reinduction Block II

Participants undergo a second reinduction therapy to ensure minimal residual disease

6 weeks

Consolidation II

Participants receive additional consolidation therapy to maintain remission

12 weeks

Maintenance

Participants receive maintenance therapy to prevent relapse over a long-term period

3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• Blinatumomab

Trial Overview The TINI 2 study aims to improve the initial TINI study by testing blinatumomab's effectiveness in clearing persistent leukemia. Blinatumomab is an immunotherapy that targets CD19 on the surface of leukemia cells, along with other drugs like Mercaptopurine and Methotrexate.

Participant Groups

Group I: Treatment Experimental Treatment 9 Interventions

Participants who meet eligibility criteria will receive remission induction, induction intensification, consolidation I, reinduction block I, reinduction block II, consolidation II, and Maintenance. Interventions: Dexamethasone, Mitoxantrone, PEG-asparaginase, Bortezomib, Vorinostat, Mercaptopurine, Methotrexate and Vincristine, Blinatumomab, Ziftomenib

Who Is Running the Clinical Trial?

Tanja Andrea Gruber

Lead Sponsor

Trials

2

Recruited

110+

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Lucile Packard Children's Hospital Foundation

Collaborator

Trials

1

Recruited

90+

Kura Oncology

Collaborator

Trials

2

Recruited

110+

Kura Oncology, Inc.

Industry Sponsor

Trials

19

Recruited

1,700+

Amgen

Industry Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Pediatric Oncology Experimental Therapeutics Investigators' Consortium

Collaborator

Trials

3

Recruited

120+

Lucile Packard Foundation for Children's Health

Collaborator

Trials

1

Recruited

90+

Findings from Research

In a study of 23 adults with B-cell acute lymphoblastic leukemia treated with blinatumomab, pre-emptive intravenous immune globulin (IVIG) did not reduce the incidence of hypogammaglobulinemia or associated infections compared to a control group.

Both groups experienced similar rates of infections and immunoglobulin levels, indicating that IVIG repletion may not be effective in mitigating the risks associated with blinatumomab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunoglobulin repletion during blinatumomab therapy does not reduce the rate of secondary hypogammaglobulinemia and associated infectious risk. Wo, S., Levavi, H., Mascarenhas, J., et al.[2022]

In a study of 33 children with refractory or relapsed precursor B-cell acute lymphoblastic leukemia (R/R-BCP-ALL), a short course of blinatumomab resulted in a high complete remission rate of 78.8%, with remission lasting approximately 14 days.

The treatment was associated with manageable side effects, including cytokine release syndrome in 54.5% of patients, but no treatment-related deaths, indicating that blinatumomab is both effective and safe for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-course blinatumomab for refractory/relapse precursor B acute lymphoblastic leukemia in children. Xie, J., Liu, S., Zhou, M., et al.[2023]

Blinatumomab, a bispecific T-cell engager, significantly improves overall survival in adults and children with relapsed and refractory B-cell acute lymphoblastic leukemia (ALL), showing a median overall survival of 7.7 months compared to 4.0 months with standard chemotherapy.

The drug achieved a complete measurable residual disease response in 78% of patients in the phase II BLAST trial, but it is associated with potential side effects, including cytokine release syndrome and neurotoxicity in about 15% and 65% of patients, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of Blinatumomab in the Treatment of Acute Lymphoblastic Leukemia: Engaging an Old Problem With New Solutions. Halford, Z., Coalter, C., Gresham, V., et al.[2021]

Blinatumomab (Blina) is a safe and effective first-line treatment for children and young persons with chemotherapy-intolerant or chemotherapy-resistant B-ALL, showing high response rates (97%) in patients with minimal residual disease before treatment.

In a study of 105 patients, those treated with Blina had similar event-free survival (EFS) and overall survival (OS) rates compared to matched controls receiving standard chemotherapy, indicating that Blina can be a viable alternative to intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab for First-Line Treatment of Children and Young Persons With B-ALL. Hodder, A., Mishra, AK., Enshaei, A., et al.[2023]

In a study involving 13 infants with acute lymphoblastic leukaemia (ALL), blinatumomab treatment followed by hematopoietic stem cell transplantation led to a complete minimal residual disease (MRD) response in patients with slow MRD clearance, resulting in an 18-month event-free survival rate of 75%.

However, the treatment was less effective in patients with relapsed or refractory ALL, as only one out of five remained in complete remission, highlighting the need for further research on immunotherapy for high-risk infant ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab following haematopoietic stem cell transplantation - a novel approach for the treatment of acute lymphoblastic leukaemia in infants. Popov, A., Fominikh, V., Mikhailova, E., et al.[2021]

Blinatumomab shows a favorable safety profile in pediatric patients with B-cell acute lymphoblastic leukemia (ALL), associated with a lower risk of serious adverse events, febrile neutropenia, and infections compared to traditional chemotherapy.

While blinatumomab does not significantly increase the risk of cytokine release syndrome or seizures, it is linked to a higher risk of encephalopathy, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of blinatumomab in pediatric patients with acute lymphoblastic leukemia: A systematic review and meta-analysis. Marrapodi, MM., Mascolo, A., di Mauro, G., et al.[2022]

Blinatumomab (Blincyto) received accelerated FDA approval for treating relapsed or refractory precursor B-cell acute lymphoblastic leukemia (R/R ALL) based on a trial with 185 adults, showing a complete remission rate of 32% and a median response duration of 6.7 months.

While blinatumomab is effective, it is associated with serious side effects like cytokine release syndrome and neurological events, along with common adverse reactions such as fever, headache, and neutropenia, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval: Blinatumomab. Przepiorka, D., Ko, CW., Deisseroth, A., et al.[2021]

Blinatumomab (Blincyto) achieved a complete remission in 33% of patients with relapsed or refractory Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (ALL), indicating its efficacy as a treatment option.

However, the treatment is associated with frequent grade 3 or 4 adverse effects, highlighting the need for careful monitoring of patients during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab (Blincyto) for acute lymphoblastic leukemia. [2015]

Blinatumomab is an effective treatment for patients with relapsed or refractory Philadelphia chromosome-negative B-cell acute lymphocytic leukemia (ALL), as demonstrated in two phase II clinical trials.

Patients who achieve remission with blinatumomab may be eligible for stem cell transplantation, offering a potential cure for their leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab: A New Treatment for Adults With Relapsed Acute Lymphocytic Leukemia. Turner, J., Schneider, SM.[2017]

Blinatumomab (Blincyto) received accelerated approval for treating B-cell precursor acute lymphoblastic leukemia (ALL) in patients with minimal residual disease, highlighting its efficacy in maintaining remission in both adults and children.

As a bispecific CD19-directed CD3 T-cell engager, blinatumomab works by activating T-cells to target and eliminate leukemia cells, demonstrating a novel mechanism of action in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A closer look at blinatumomab. Mattison, RJ.[2018]

Blinatumomab (Blincyto®) is an effective treatment for relapsed or refractory acute lymphoblastic leukemia, having received accelerated approval for its use.

A multidisciplinary collaboration among nursing, pharmacy, prescribers, and support staff is essential for the safe administration of blinatumomab, and this approach can be adapted by other institutions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Multidisciplinary Approach to Standardizing Processes for Blinatumomab Administration. DePadova, S., Howlett, C., Rivera, K.[2017]

In a study involving 255 patients aged 1-30 with low-risk first relapse of B-cell acute lymphoblastic leukemia (B-ALL), blinatumomab combined with chemotherapy showed a significant improvement in disease-free survival (DFS) and overall survival (OS) for patients with bone marrow and extramedullary relapses compared to chemotherapy alone.

Blinatumomab was well tolerated with low adverse event rates, but no significant difference in outcomes was found for patients with isolated extramedullary relapses, indicating a need for new treatment strategies for this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Children's Oncology Group AALL1331: Phase III Trial of Blinatumomab in Children, Adolescents, and Young Adults With Low-Risk B-Cell ALL in First Relapse. Hogan, LE., Brown, PA., Ji, L., et al.[2023]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

Immunoglobulin repletion during blinatumomab therapy does not reduce the rate of secondary hypogammaglobulinemia and associated infectious risk. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Short-course blinatumomab for refractory/relapse precursor B acute lymphoblastic leukemia in children. [2023]

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

A Systematic Review of Blinatumomab in the Treatment of Acute Lymphoblastic Leukemia: Engaging an Old Problem With New Solutions. [2021]

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

Blinatumomab for First-Line Treatment of Children and Young Persons With B-ALL. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Blinatumomab following haematopoietic stem cell transplantation - a novel approach for the treatment of acute lymphoblastic leukaemia in infants. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

The safety of blinatumomab in pediatric patients with acute lymphoblastic leukemia: A systematic review and meta-analysis. [2022]

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

FDA Approval: Blinatumomab. [2021]

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

Blinatumomab (Blincyto) for acute lymphoblastic leukemia. [2015]

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

Blinatumomab: A New Treatment for Adults With Relapsed Acute Lymphocytic Leukemia. [2017]

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

A closer look at blinatumomab. [2018]

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

A Multidisciplinary Approach to Standardizing Processes for Blinatumomab Administration. [2017]

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

Children's Oncology Group AALL1331: Phase III Trial of Blinatumomab in Children, Adolescents, and Young Adults With Low-Risk B-Cell ALL in First Relapse. [2023]