Blinatumomab + Other Treatments for Blood Cancers

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: St. Jude Children's Research Hospital

Disqualifiers: Active malignancy, Prior allogeneic HCT, 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

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of a new treatment approach for certain blood cancers. It combines an early cell infusion (a type of immune cell transfer) with the drug blinatumomab (a type of immunotherapy) to determine if it is safe and can be administered soon after a transplant. The trial seeks young patients (21 or younger) with high-risk blood cancers, such as certain types of leukemia, who have already undergone a transplant and may lack other donor options. Participants should have blood cancers involving CD19+ cells, which blinatumomab targets. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment approach.

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

The trial information does not specify whether 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 blinatumomab is generally safe for individuals with certain blood cancers. In past studies, some patients discontinued its use due to side effects, but many continued without major issues. Another study found that blinatumomab could be safely administered to patients outside of clinical trials, indicating broad safety.

Although this treatment is still undergoing early trials, evidence suggests it is usually well-tolerated. Prospective trial participants should discuss the benefits and potential risks with their healthcare provider, considering their personal health. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Blinatumomab is unique because it specifically targets CD19+ cells, which are often found in certain blood cancers. Unlike traditional chemotherapy that attacks rapidly dividing cells in general, Blinatumomab functions as a bispecific T-cell engager (BiTE), directly linking T-cells to cancer cells, which can lead to more precise destruction of malignant cells. Researchers are excited about Blinatumomab because it offers a more targeted approach, potentially leading to fewer side effects and improved outcomes for patients with CD19+ malignancies.

What evidence suggests that this trial's treatments could be effective for blood cancers?

Studies have shown that blinatumomab effectively treats certain blood cancers, particularly B-cell acute lymphoblastic leukemia (B-ALL). This drug enables the immune system's T-cells to locate and destroy cancer cells with the CD19 protein. Research indicates that blinatumomab has improved survival rates compared to traditional chemotherapy for patients whose B-ALL has returned or not responded to treatment. Some studies found that over 90% of B-cell precursor ALL cases had CD19, making them suitable candidates for this treatment. In this trial, researchers will empirically add blinatumomab for patients with CD19+ malignancy, offering hope as a strong option for those with CD19+ blood cancers. ^{4 5 6 7 8}

Who Is on the Research Team?

Brandon Triplett, MD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

This trial is for individuals with blood cancers who are undergoing a specific type of bone marrow transplant from partially matched donors. Participants should not have received this transplant before and must be fit enough for the procedure.

Inclusion Criteria

Donor: Completed donor eligibility determination as per regulatory requirements or has a declaration of urgent medical need

My lung function is at least half of what is expected, or my oxygen level is 92% or higher without extra oxygen.

I am HIV negative.

Exclusion Criteria

I do not have any ongoing serious infections.

I have a matching donor for my transplant.

I do not have any other active cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparative Regimen

Participants receive a preparative regimen consisting of antibodies and chemotherapy prior to donor cell infusion

12 days

Daily visits for treatment administration

Transplantation

TCRαβ-depleted haploidentical donor product is infused, with potential additional infusion on day +1

1-2 days

Inpatient stay for transplantation

Early Memory T-cell DLI

Memory cell donor lymphocyte infusion (DLI) is administered approximately 2 weeks post-transplant

1 day

Inpatient or outpatient visit for DLI administration

Blinatumomab Administration

Blinatumomab is added for patients with CD19+ malignancy at least four weeks after DLI

Variable, based on patient response

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 180 days post-transplant

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Blinatumomab

Trial Overview The study tests the safety of giving patients special immune cells (early memory T-cells) after their transplant, and in some cases, an additional drug called Blinatumomab if they have CD19+ cancer. It also looks at how well a drug used to prevent rejection (rabbit ATG) works in these patients.

How Is the Trial Designed?

Group I: HAP3HCT Treatment Experimental Treatment 9 Interventions

Prior to the infusion of donor cells, a preparative regimen consisting of antibodies and chemotherapy will be given. The preparative regimen includes the following total dosages: ATG 5mg/kg (over days -12 to -10); Cyclophosphamide 60 mg/kg (day -9); Fludarabine 150 mg/m2 (over days -8 to -4); Thiotepa 10 mg/kg (divided in two doses on day -3); Melphalan 70 mg/m2 (over days -2 to -1). Following this regimen the TCRαβ-depleted haploidentical donor product will be given on day 0 (subsequent infusion given on day +1 if needed to achieve goal CD34+ cell dose. Approximately 2 weeks later the memory cell donor lymphocyte infusion (DLI) will be given at a dose previously determined to be safe and effective. Blinatumomab will be empirically added for patients with CD19+ malignancy and given at least four weeks after the memory cell DLI.

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4485855/

Blinatumomab in Relapsed/Refractory ALL - PMC More than 90% of cases of BCP ALL express CD19 in more than 20% of malignant cells, the intensity of expression being sufficient to make this therapy suitable ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0145212625005880

Efficacy and safety of blinatumomab for CD19 + acute ... The CD3-CD19 bispecific engager blinatumomab has helped improve outcomes for patients with B-cell acute lymphoblastic leukemia (B-ALL) in various treatment ...

3. ashpublications.org ashpublications.org/blood/article/132/Supplement%201/5209/265467/Safety-and-Efficacy-of-Blinatumomab-Real-World

Safety and Efficacy of Blinatumomab- Real World Data | Blood Blinatumomab, a bispecific monoclonal antibody directed against CD19 ... Blood Neoplasia · Blood Red Cells & Iron · Blood Vessels, Thrombosis ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1609783

Blinatumomab vs. Chemo for Acute Lymphoblastic Leukemia Treatment with blinatumomab resulted in significantly longer overall survival than chemotherapy among adult patients with relapsed or refractory B-cell ...

5. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-blinatumomab-consolidation-cd19-positive-philadelphia-chromosome-negative-b-cell

FDA approves blinatumomab as consolidation for CD19 ... The major efficacy outcome measures were OS and relapse-free survival (RFS). The 5‑year OS was 78.4% (95% CI: 64.2, 87.4) and 41.4% (95% CI: 26 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40961730/

Efficacy and safety of blinatumomab for CD19 + acute ... One patient stopped prematurely due to toxicity and three due to lack of response in the relapsed/refractory setting. Response rates and survival were similar ...

7. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/5889/527631/A-Systematic-Review-on-Efficacy-and-Safety-Profile

A Systematic Review on Efficacy and Safety Profile of ... Blinatumomab treatment showed a median Overall Survival (mOS) of 10.35 months and a median Relapse-Free Survival (mRFS) of 12.7 months. The most ...

8. nature.com nature.com/articles/s41408-024-01127-2

Safety and efficacy of blinatumomab as bridge-to- ... Many studies have shown that blinatumomab is effective in eliminating MRD and improving the prognosis in B-ALL [3, 4]. Additionally, recent ...