Blinatumomab + Inotuzumab Ozogamicin + Chemotherapy for Leukemia

Recruiting in Palo Alto (17 mi)

Overseen by Elias Jabbour, MD

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: M.D. Anderson Cancer Center

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

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well blinatumomab, inotuzumab ozogamicin, and combination chemotherapy work as frontline therapy in treating patients with B acute lymphoblastic leukemia. Immunotherapy with monoclonal antibodies, such as blinatumomab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a toxic agent called ozogamicin. Inotuzumab attaches to CD22 positive cancer cells in a targeted way and delivers ozogamicin to kill them. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, dexamethasone, cytarabine, mercaptopurine, methotrexate, and prednisone work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving blinatumomab, inotuzumab ozogamicin, and combination chemotherapy may work better in treating patients with B acute lymphoblastic leukemia than chemotherapy alone.

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.

What data supports the effectiveness of the drug combination Blinatumomab, Inotuzumab Ozogamicin, and Chemotherapy for treating leukemia?

Research shows that Blinatumomab and Inotuzumab Ozogamicin have improved outcomes in patients with relapsed or refractory acute lymphoblastic leukemia (ALL), with studies indicating they can help achieve remission and serve as a bridge to stem cell transplantation. In children, these drugs have shown promise in reducing disease levels and avoiding further toxic chemotherapy.

^{1 2 3 4 5}

Is the combination of Blinatumomab and Inotuzumab Ozogamicin safe for humans?

Research shows that Blinatumomab and Inotuzumab Ozogamicin have been used safely in treating certain types of leukemia, with some patients experiencing reversible side effects. These treatments have been studied in both adults and children, showing promise as alternatives to traditional chemotherapy.

^{1 2 3 4 6}

What makes the drug combination of Blinatumomab, Cyclophosphamide, and Inotuzumab Ozogamicin unique for treating leukemia?

This drug combination is unique because it combines Blinatumomab, which helps the immune system target cancer cells, with Inotuzumab Ozogamicin, an antibody-drug conjugate that delivers chemotherapy directly to cancer cells, and Cyclophosphamide, a traditional chemotherapy drug, offering a multi-faceted approach to treating relapsed or refractory B-cell acute lymphoblastic leukemia.

^{1 2 3 6 7}

Eligibility Criteria

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.

Trial Timeline

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

Participant Groups

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.

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)

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

M D Anderson Cancer Center Houston, TX

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center Lead Sponsor

National Cancer Institute (NCI) Collaborator

References

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

Indirect Treatment Comparison of Inotuzumab Ozogamicin Versus Blinatumomab for Relapsed or Refractory Acute Lymphoblastic Leukemia. [2020] No head-to-head studies have compared inotuzumab ozogamicin (InO) and blinatumomab (Blina) for the treatment of adults with relapsed or refractory B cell precursor acute lymphoblastic leukemia (ALL). Indirect treatment comparisons (ITCs), namely network meta-analysis (NMA), anchored matching-adjusted indirect comparison (MAIC), and simulated treatment comparison (STC), were conducted to compare the relative efficacy of these therapies.

2. Switzerland 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. [2023] Blinatumomab (Blina) and inotuzumab ozogamicin (InO) has improved the outcome of relapsed/refractory B-lymphoblastic leukemia (R/R B-ALL). However, little is known about the outcome after recurrence and re-treatment with immunotherapy.

3. United States 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. [2021] Blinatumomab and inotuzumab ozogamicin are now widely used to treat relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL).

4. England 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). [2021] Blinatumomab and inotuzumab ozogamycin represent promising alternatives to conventional chemotherapy in acute lymphoblastic leukaemia (ALL). We analysed data from 29 children with ALL treated under compassionate use with blinatumomab, inotuzumab or both. The complete remission (CR) rate in a heavily pretreated population with overt relapse was 47·6%. At earlier stages (first/second CR), both antibodies represented a useful tool to reduce minimal residual disease, and/or avoid further toxic chemotherapy until stem cell transplantation. Six patients developed grade 3 reversible non-haematological toxicity. The 12-month overall survival and event-free survival rates were 50·8 ± 26·4% and 38·9 ± 25·3% with blinatumomab, 45·8 ± 26% and 27·5 ± 25% with inotuzumab.

5. England 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. [2023] Historically, adults with relapsed-refractory acute lymphoblastic leukemia (ALL) experienced poor outcomes with intensive chemotherapy. This mature analysis explores the benefit of the addition of sequential blinatumomab to low-intensity mini-Hyper-CVD chemotherapy with inotuzumab ozogamicin in this setting.

6. New Zealand 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. [2023] The TOWER and INO-VATE-ALL trials demonstrated the efficacy and safety of blinatumomab and inotuzumab ozogamicin (inotuzumab), respectively, versus standard-of-care (SOC) chemotherapy in adults with relapsed or refractory (R/R) B-cell precursor acute lymphoblastic leukemia (ALL). The cost effectiveness of blinatumomab versus inotuzumab has not previously been examined.

7. United States 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. [2019] PURPOSE Inotuzumab ozogamicin (CMC-544) is an antibody-targeted chemotherapy agent composed of a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. This was a phase I study to determine the maximum-tolerated dose (MTD), safety, and preliminary efficacy of inotuzumab ozogamicin in an expanded MTD cohort of patients with relapsed or refractory CD22(+) B-cell non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS Inotuzumab ozogamicin was administered intravenously as a single agent once every 3 or 4 weeks at doses ranging from 0.4 to 2.4 mg/m(2). Outcomes included MTD, safety, pharmacokinetics, response, progression-free survival (PFS), and overall survival. Results Seventy-nine patients were enrolled. The MTD was determined to be 1.8 mg/m(2). Common adverse events at the MTD were thrombocytopenia (90%), asthenia (67%), and nausea and neutropenia (51% each). The objective response rate at the end of treatment was 39% for the 79 enrolled patients, 68% for all patients with follicular NHL treated at the MTD, and 15% for all patients with diffuse large B-cell lymphoma treated at the MTD. Median PFS was 317 days (approximately 10.4 months) and 49 days for patients with follicular NHL and diffuse large B-cell lymphoma, respectively. CONCLUSION Inotuzumab ozogamicin has demonstrated efficacy against CD22(+) B-cell NHL, with reversible thrombocytopenia as the main toxicity.