Blinatumomab + Inotuzumab Ozogamicin + Chemotherapy for Leukemia

Overseen By Elias Jabbour, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Pregnancy, HIV-positive, Ph-positive ALL, 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

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

Compensation: Varies

Number of Visits: Unknown

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for B acute lymphoblastic leukemia (ALL), a type of blood cancer. Researchers are testing whether a combination of blinatumomab (an immunotherapy), inotuzumab ozogamicin (a targeted antibody linked to a toxin), and traditional chemotherapy can fight leukemia more effectively than chemotherapy alone. The trial aims to determine if this combination can better stop cancer from growing and spreading compared to current treatments. Individuals newly diagnosed with B-lineage ALL or those who have relapsed after initial treatment might be suitable for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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 shows that the combination of blinatumomab, inotuzumab ozogamicin, and chemotherapy is generally well-tolerated in people with B acute lymphoblastic leukemia. Studies have found that using blinatumomab and inotuzumab ozogamicin together improves outcomes for patients whose leukemia has returned or is not responding to treatment. These studies found the treatment both safe and effective.

Blinatumomab is a type of immunotherapy that helps the immune system fight cancer. Inotuzumab ozogamicin is a targeted therapy, specifically attacking cancer cells. Cyclophosphamide is a common chemotherapy drug that stops cancer cells from growing.

While side effects can occur, as with any treatment, the safety of this combination has been consistent. Reported side effects are generally manageable. These findings suggest that the treatment is a viable option for many patients, though individual experiences may vary. Patients should always discuss potential side effects with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Blinatumomab and Inotuzumab Ozogamicin with chemotherapy for leukemia because it targets cancer cells more precisely than traditional options. Blinatumomab is a bispecific T-cell engager that brings T-cells directly to leukemia cells, enhancing the body's immune response. Inotuzumab Ozogamicin is an antibody-drug conjugate that delivers chemotherapy directly to cancerous cells, minimizing damage to healthy cells. This dual approach could lead to more effective treatment outcomes with potentially fewer side effects compared to standard chemotherapy alone.

What evidence suggests that this trial's treatments could be effective for B acute lymphoblastic leukemia?

Research has shown that using the drugs blinatumomab and inotuzumab ozogamicin together may be promising for treating B acute lymphoblastic leukemia, a type of blood cancer. In this trial, participants will receive a combination of blinatumomab, inotuzumab ozogamicin, and chemotherapy. A large review of past studies found that 76% of patients responded to these treatments. One study found that 85% of patients achieved complete remission with inotuzumab ozogamicin, while 97% did so with blinatumomab. These treatments specifically target and kill cancer cells, potentially increasing their effectiveness. Combining these drugs with chemotherapy might provide better results than using chemotherapy alone. ^{3 6 7 8}

Who Is on the Research Team?

Elias Jabbour, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with newly diagnosed B acute lymphoblastic leukemia or those who've achieved remission after one chemotherapy course. Eligible participants must have a performance status of 0-3, creatinine ≤2.0 mg/dL, bilirubin ≤2.0 mg/dL, and adequate cardiac function. Exclusions include HIV-positive individuals, active uncontrolled diseases/infections, CNS pathology like epilepsy or stroke, current autoimmune disease with potential CNS involvement, pregnant/nursing women, Philadelphia chromosome-positive ALL.

Inclusion Criteria

I have B-lineage ALL or lymphoblastic lymphoma, untreated or in complete remission after one chemotherapy course.

I can care for myself but may not be able to do heavy physical work.

Creatinine less than or equal to 2.0 mg/dL (unless considered tumor related)

Exclusion Criteria

I weigh less than 45 kg.

I do not have active liver or bile duct disease, except for Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease.

I have an autoimmune disease that affects my brain or nervous system.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intensive Phase

Patients receive hyper-CVAD regimen including cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, dexamethasone, methotrexate, and cytarabine, with optional ofatumumab or rituximab

12 weeks

Multiple visits for IV administration

Blinatumomab and Inotuzumab Ozogamicin Phase

Patients receive blinatumomab and inotuzumab ozogamicin over 4 cycles

24 weeks

Continuous IV administration and bi-weekly visits

Maintenance Phase

Patients may receive maintenance therapy with mercaptopurine, methotrexate, vincristine sulfate, and prednisone, with blinatumomab after every 3 cycles

12 months

Monthly visits for IV administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Monthly follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Blinatumomab
• Cyclophosphamide
• Inotuzumab Ozogamicin

Trial Overview The study tests blinatumomab and inotuzumab ozogamicin combined with chemotherapy drugs (cyclophosphamide to prednisone) as initial treatment for B acute lymphoblastic leukemia. Blinatumomab modifies the immune system to target cancer cells; inotuzumab ozogamicin delivers toxins directly to cancer cells via CD22 binding.

How Is the Trial Designed?

Group I: Treatment (blinatumomab, inotuzumab, combination chemotherapy) Experimental Treatment 13 Interventions

See detailed description.

Blinatumomab is already approved in European Union, United States for the following indications:

Approved in European Union as Blincyto for:

• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL)
• High-risk first relapse BCP-ALL

Approved in United States as Blincyto for:

• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL)
• First or second complete remission with minimal residual disease (MRD)

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Inotuzumab ozogamicin (InO) demonstrated significantly higher rates of remission and hematopoietic stem cell transplantation (HSCT) compared to blinatumomab (Blina) in adults with relapsed or refractory B cell precursor acute lymphoblastic leukemia (ALL), based on indirect treatment comparisons involving patient-level data from 746 participants.

While both treatments showed similar overall survival rates, the analyses indicated a trend favoring InO for event-free survival, suggesting it may offer better outcomes in terms of remission and subsequent treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indirect Treatment Comparison of Inotuzumab Ozogamicin Versus Blinatumomab for Relapsed or Refractory Acute Lymphoblastic Leukemia. Proskorovsky, I., Su, Y., Fahrbach, K., et al.[2020]

In a study of 29 children with acute lymphoblastic leukaemia (ALL) treated with blinatumomab and/or inotuzumab, the complete remission rate was 47.6%, indicating these therapies can be effective alternatives to traditional chemotherapy, especially in heavily pretreated patients.

Both treatments showed promise in reducing minimal residual disease and delaying further chemotherapy, with manageable safety profiles, as only six patients experienced grade 3 reversible non-haematological toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab and inotuzumab for B cell precursor acute lymphoblastic leukaemia in children: a retrospective study from the Leukemia Working Group of the Spanish Society of Pediatric Hematology and Oncology (SEHOP). Fuster, JL., Molinos-Quintana, A., Fuentes, C., et al.[2021]

In a study of 34 adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), blinatumomab achieved a complete remission (CR) rate of 69%, with 78% of those patients reaching minimal residual disease (MRD) negativity, indicating effective treatment outcomes.

Inotuzumab ozogamicin showed an even higher CR rate of 94% in patients with overt r/r B-ALL, with 67% achieving MRD negativity, suggesting both treatments are highly effective salvage options for this aggressive leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab or Inotuzumab Ozogamicin as Bridge to Allogeneic Stem Cell Transplantation for Relapsed or Refractory B-lineage Acute Lymphoblastic Leukemia: A Retrospective Single-Center Analysis. Stelmach, P., Wethmar, K., Groth, C., et al.[2021]

In a study of 71 patients with relapsed/refractory B-lymphoblastic leukemia, treatment with blinatumomab (Blina) and inotuzumab ozogamicin (InO) resulted in high rates of complete remission (CR), with 63% achieving CR after Blina and 82% after InO, indicating strong efficacy for these immunotherapies.

The median overall survival for patients treated with Blina/InO was 19 months, and the disease-free survival was significantly better for patients with negative minimal residual disease (MRD-) compared to those with positive MRD, highlighting the importance of MRD status in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab and Inotuzumab Ozogamicin Sequential Use for the Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia: A Real-Life Campus All Study. Fracchiolla, NS., Sciumè, M., Papayannidis, C., et al.[2023]

Blinatumomab is estimated to be cost-effective compared to inotuzumab for treating adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia, with cost-effectiveness ranging from $4006 to $20,737 per quality-adjusted life-year (QALY) gained.

The analysis was based on a comprehensive model using data from the TOWER and INO-VATE-ALL trials, which included health outcomes like complete remission rates and overall survival, adjusted to match patient populations, indicating a thorough evaluation of both efficacy and economic impact.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost Effectiveness of Blinatumomab Versus Inotuzumab Ozogamicin in Adult Patients with Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia in the United States. Delea, TE., Zhang, X., Amdahl, J., et al.[2023]

Inotuzumab ozogamicin, an antibody-targeted chemotherapy, was found to be effective in treating relapsed or refractory CD22(+) B-cell non-Hodgkin's lymphoma, with an objective response rate of 39% overall and 68% specifically for follicular NHL.

The maximum-tolerated dose was established at 1.8 mg/m², with thrombocytopenia being the most common side effect, affecting 90% of patients, indicating that while the treatment is effective, careful monitoring of blood cell counts is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and preliminary clinical activity of inotuzumab ozogamicin, a novel immunoconjugate for the treatment of B-cell non-Hodgkin's lymphoma: results of a phase I study. Advani, A., Coiffier, B., Czuczman, MS., et al.[2019]

In a study of 110 adults with relapsed-refractory acute lymphoblastic leukemia (ALL), the combination of low-intensity mini-Hyper-CVD chemotherapy and inotuzumab resulted in an 83% response rate, with 63% achieving complete response and 82% of responders showing no measurable residual disease.

The addition of sequential blinatumomab improved overall survival rates, with a 3-year overall survival of 52% compared to 34% for those receiving only mini-Hyper-CVD plus inotuzumab, indicating that blinatumomab enhances treatment efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of salvage therapy with mini-hyper-CVD and inotuzumab ozogamicin with or without blinatumomab in pre-B acute lymphoblastic leukemia. Kantarjian, H., Haddad, FG., Jain, N., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6824351/

Matching-Adjusted Indirect Comparison of Blinatumomab vs ... In the absence of head-to-head trials, this analysis aimed to provide a fair indirect comparison of the efficacy between blinatumomab and inotuzumab ozogamicin ...

2. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO-25-00307

Inotuzumab Ozogamicin Then Blinatumomab for Older ... The composite complete remission rate was 85% after two cycles of inotuzumab ozogamicin and 97% by the end of two cycles of blinatumomab. At a ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10526797/

Blinatumomab and Inotuzumab Ozogamicin Sequential ... A recent large meta-analysis analyzed the results of 38 reports, which enrolled 2134 patients. An overall response rate of 76% was reported, ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2152265024024662

Inotuzumab Ozogamicin as First-Line Therapy in Acute ... They reported a significantly better OS in patients receiving blinatumomab (estimated 5-year OS rates were 80% vs. 55%). In MRD-negative patients aged > 55 ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6541

Outcomes in patients with B-cell precursor acute ... In this pooled analysis of pts treated with InO for R/R B-ALL, efficacy and safety outcomes were broadly consistent across BMI groups.

6. trialx.com trialx.com/clinical-trials/listings/254806/blinatumomab-inotuzumab-ozogamicin-and-combination-chemotherapy-as-frontline-therapy-in-treating-patients-with-b-acute-lymphoblastic-leukemia/?&radius=50

Blinatumomab, Inotuzumab Ozogamicin, and Combination ... This phase II trial studies how well blinatumomab, inotuzumab ozogamicin, and combination chemotherapy work as frontline therapy in treating ...

7. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/2811/531826/Updated-Results-of-the-Combination-of-Mini-Hyper

Updated Results of the Combination of Mini-Hyper-CVD with ... Conclusion: The combination of mini-HCVD, INO and Blina is safe and effective in R/R B-ALL. Introducing Blina and fractionating INO seem to ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02877303?term=6-MERCAPTOPURINE%20MONOHYDRATE&rank=9

Blinatumomab, Inotuzumab Ozogamicin, and Combination ... A phase of research to describe clinical trials that focus on the safety of a drug. They are usually conducted with healthy volunteers, and the goal is to ...