Inotuzumab + Chemotherapy for Leukemia

(ALL-001 Trial)

Recruiting at 3 trial locations

Overseen By Amy Smith, BS

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Virginia

Must not be taking: Steroids, Hydroxyurea

Disqualifiers: Pancreatitis, Congestive heart failure, 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

Duration: 4 weeks

36 Participants Needed

Trial Summary

What is the purpose of this trial?

In the proposed study, escalating doses of inotuzumab ozogamicin will be added to a standard pediatric inspired re-induction regimen and administered to patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). Two re-induction regimens will be tested (one without pegaspargase and one including pegaspargase) and participants will be followed for disease status, allogeneic hematopoietic cell transplant (allo HCT), veno-occlusive disease following allo HCT, and overall survival.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking steroids or hydroxyurea, you must not have used them for more than 7 days within the 2 weeks before joining the trial.

What data supports the effectiveness of the drug Inotuzumab ozogamicin for leukemia?

Inotuzumab ozogamicin has been shown to improve response rates, survival, and the chance of proceeding to a stem cell transplant in patients with relapsed or refractory acute lymphoblastic leukemia (ALL) compared to standard chemotherapy. It has demonstrated improved complete remission rates and overall survival in clinical trials for this condition. ^{1 2 3 4 5}

Is Inotuzumab ozogamicin safe for humans?

Inotuzumab ozogamicin has been studied for safety in patients with certain types of leukemia and lymphoma. Common side effects include low blood cell counts, liver problems, and other blood-related issues. It has shown some safety concerns, especially when combined with other treatments, but it is generally considered tolerable in clinical settings. ^{4 5 6 7 8}

How is the drug Inotuzumab ozogamicin different from other treatments for leukemia?

Inotuzumab ozogamicin is unique because it is a targeted therapy that combines an antibody with a powerful drug to specifically attack leukemia cells that have a marker called CD22, which is present in most patients with this type of leukemia. This approach can improve outcomes for patients whose disease has returned or not responded to standard treatments. ^{3 9 10 11 12}

Research Team

Michael Douvas, MD

Principal Investigator

University of Virginia

Eligibility Criteria

This trial is for individuals aged 16-60 with relapsed/refractory B-cell acute lymphoblastic leukemia or lymphoma, CD-22 positive, and without major heart, liver, or kidney issues. They must be able to follow the study plan and agree to use contraception. Exclusions include active infections, prior stem cell transplant, certain heart conditions, allergies to asparaginase (for part 2), pregnancy/lactation, chronic liver disease/hepatitis B/C virus infection.

Inclusion Criteria

Left ventricular ejection fraction ≥ 50% measured by echocardiogram or MUGA

For females and males of reproductive potential: agreement to use adequate contraception during study participation and for an additional 1 year after the end of study treatment

My kidney and liver functions are within the required limits.

Exclusion Criteria

I have been diagnosed with HIV.

I have been diagnosed with congestive heart failure.

I do not have any active or uncontrolled infections.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive escalating doses of inotuzumab ozogamicin added to a standard pediatric inspired re-induction regimen

4 weeks

Weekly visits for drug administration and monitoring

Follow-up

Participants are monitored for safety, disease status, and adverse events after treatment

4 weeks

Bi-weekly visits for monitoring

Long-term follow-up

Participants are followed for overall survival and veno-occlusive disease following allo HCT

Long-term

Treatment Details

Interventions

• Inotuzumab ozogamicin

Trial Overview The trial tests different doses of Inotuzumab ozogamicin added to a re-induction regimen for treating B-cell ALL. It explores two regimens: one with pegaspargase and one without it. The focus is on how well patients respond to treatment including their survival rates and potential complications after stem cell transplants.

Participant Groups

Group I: 4-drug re-induction regimen with inotuzumab Experimental Treatment 7 Interventions

One cycle of a 4-drug regimen comprised of standard doses of prednisone, vincristine, daunorubicin, and pegaspargase with inotuzumab ozogamicin at a reduced dose. Intrathecal methotrexate (IT-methotrexate) and intrathecal cytarabine (IT-Ara-C) will be included for CNS prophylaxis. IV inotuzumab ozogamicin will be given at a reduced dose (may vary from a total cycle dose of 0.4 mg/m\^2 to 0.9 mg/m\^2)

Group II: 3-drug re-induction regimen with inotuzumab Experimental Treatment 6 Interventions

One cycle of a 3-drug regimen comprised of standard doses of prednisone, vincristine, and daunorubicin with inotuzumab ozogamicin at a reduced dose. Intrathecal methotrexate (IT-methotrexate) and intrathecal cytarabine (IT-Ara-C) will be included for CNS prophylaxis. IV inotuzumab ozogamicin will be given at a reduced dose (may vary from a total cycle dose of 0.4 mg/m\^2 to 0.9 mg/m\^2)

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

Approved in United States as Besponsa for:

• Adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL)
• Pediatric patients 1 year and older with relapsed or refractory CD22-positive BCP-ALL

Approved in European Union as Besponsa for:

• Adults with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL)

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

University of Wisconsin, Madison

Collaborator

Trials

1,249

Recruited

3,255,000+

Virginia Commonwealth University

Collaborator

Trials

732

Recruited

22,900,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Vanderbilt University

Collaborator

Trials

714

Recruited

6,143,000+

Findings from Research

Inotuzumab ozogamicin, a CD22-targeting antibody-drug conjugate, has been approved for treating adults with relapsed or refractory acute lymphoblastic leukemia (ALL) and shows improved response rates and survival compared to standard chemotherapy.

This treatment not only enhances the chances of achieving minimal residual disease negativity but also increases the likelihood of patients being eligible for allogeneic stem cell transplants, which can be crucial for their long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inotuzumab Ozogamicin in Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia. Williams, S., Kim, M.[2020]

Inotuzumab ozogamicin, a targeted immunotherapy using a CD22 monoclonal antibody, has shown improved complete remission rates and overall survival in adults with relapsed or refractory acute lymphoblastic leukemia (ALL) compared to standard chemotherapy, based on results from Phase 1/2 and Phase 3 clinical trials.

This drug targets CD22, which is present on over 90% of leukemic blasts in ALL patients, highlighting its potential effectiveness and the shift towards using targeted therapies in treating this challenging disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inotuzumab ozogamicin: a CD22 mAb-drug conjugate for adult relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Yurkiewicz, IR., Muffly, L., Liedtke, M.[2019]

Inotuzumab ozogamicin (INO) demonstrated significant efficacy in treating relapsed/refractory acute lymphocytic leukemia (ALL) and non-Hodgkin lymphoma (NHL), with complete remission rates of 67% for ALL and 28% for NHL based on a systematic review of 12 studies involving 644 patients.

The treatment was associated with manageable safety concerns, with notable adverse events including thrombocytopenia and neutropenia, but a relatively low incidence of severe hepatic complications, indicating that INO can be a viable option for patients with these types of cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Inotuzumab Ozogamicin (CMC-544) for the Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia and Non-Hodgkin Lymphoma: A Systematic Review and Meta-Analysis. Li, X., Zhou, M., Qi, J., et al.[2022]

Inotuzumab ozogamicin treatment resulted in a higher frequency of hepatotoxicity (51%) compared to standard care (34%) in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia, indicating a significant safety concern.

The incidence of severe sinusoidal obstruction syndrome was notably higher in the inotuzumab ozogamicin group (13%) compared to the standard care group (<1%), particularly after subsequent hematopoietic stem-cell transplantation, highlighting the need for careful monitoring in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatic adverse event profile of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukaemia: results from the open-label, randomised, phase 3 INO-VATE study. Kantarjian, HM., DeAngelo, DJ., Advani, AS., et al.[2022]

In a phase I trial involving 19 patients with relapsed/refractory CD22 positive B-cell non-Hodgkin lymphomas, the combination of inotuzumab ozogamicin and temsirolimus showed preliminary antitumor activity, with 39% of evaluable patients achieving partial remission.

However, the treatment was associated with significant dose-limiting toxicities, including thrombocytopenia and hypertriglyceridemia, which limited the ability to administer the drugs at therapeutically useful doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of inotuzumab ozogamicin in combination with temsirolimus in patients with relapsed or refractory CD22-positive B-cell non-Hodgkin lymphomas. Pirosa, MC., Zhang, L., Hitz, F., et al.[2022]

Inotuzumab ozogamicin (InO) is effective and well-tolerated in both younger (<55 years) and older (≥55 years) patients with relapsed/refractory acute lymphoblastic leukemia (ALL), showing similar remission rates and duration of remission across age groups.

Younger patients had a longer overall survival (OS) compared to older patients (8.6 months vs 5.6 months), and older patients experienced a higher incidence of veno-occlusive disease after hematopoietic stem cell transplantation, indicating a need for careful monitoring in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety analysis by age cohort of inotuzumab ozogamicin in patients with relapsed or refractory acute lymphoblastic leukemia enrolled in INO-VATE. Jabbour, EJ., DeAngelo, DJ., Stelljes, M., et al.[2019]

Inotuzumab ozogamicin, a targeted therapy for relapsed/refractory acute lymphoblastic leukemia, effectively binds to CD22, which is present in 90-100% of malignant B-lymphocytes, showing promise for patients who have undergone extensive prior treatments.

The therapy is generally well-tolerated, although there is a risk of veno-occlusive disease, making it a potentially beneficial option for patients seeking allogeneic stem cell transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of inotuzumab ozogamicin in the treatment of relapsed/refractory acute lymphoblastic leukemia. George, B., Kantarjian, H., Jabbour, E., et al.[2019]

Inotuzumab ozogamicin is an effective treatment for patients with relapsed or refractory acute lymphoblastic leukemia (ALL), as demonstrated in the phase III INO-VATE trial, which led to its approval for this high-risk group.

This antibody-drug conjugate works by targeting CD22 on tumor cells, leading to cell death, and ongoing trials are exploring its use in combination with low-dose chemotherapy and in earlier treatment stages to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inotuzumab ozogamicin for the treatment of patients with acute lymphocytic leukemia. Choudhry, A., O'Brien, SM.[2019]

Inotuzumab ozogamicin, an anti-CD22 antibody-drug conjugate, has shown improved outcomes in adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) compared to standard salvage chemotherapy.

The combination of inotuzumab ozogamicin with low-intensity chemotherapy is showing promise for both relapse settings and as a frontline treatment for elderly patients, potentially reducing toxicity while enhancing efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inotuzumab ozogamicin for the treatment of acute lymphoblastic leukemia. Savoy, JM., Welch, MA., Nasnas, PE., et al.[2021]

Inotuzumab ozogamicin is a promising treatment for adult acute lymphoblastic leukemia (ALL), showing effectiveness as a salvage therapy that can help more patients qualify for stem cell transplants.

Clinical trials indicate that this drug, which targets B-cell tumors, has encouraging response rates, suggesting it could be particularly beneficial for specific subpopulations of ALL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inotuzumab ozogamicin in the treatment of B-cell acute lymphoblastic leukemia. Thomas, X.[2022]

References

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

ADC Approval Likely to Spur More Research. [2019]

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

Inotuzumab Ozogamicin in Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia. [2020]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Inotuzumab ozogamicin: a CD22 mAb-drug conjugate for adult relapsed or refractory B-cell precursor acute lymphoblastic leukemia. [2019]

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

Inotuzumab ozogamicin for relapsed/refractory acute lymphoblastic leukemia: outcomes by disease burden. [2021]

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

Efficacy and Safety of Inotuzumab Ozogamicin (CMC-544) for the Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia and Non-Hodgkin Lymphoma: A Systematic Review and Meta-Analysis. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Hepatic adverse event profile of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukaemia: results from the open-label, randomised, phase 3 INO-VATE study. [2022]

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

A phase I trial of inotuzumab ozogamicin in combination with temsirolimus in patients with relapsed or refractory CD22-positive B-cell non-Hodgkin lymphomas. [2022]

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

Efficacy and safety analysis by age cohort of inotuzumab ozogamicin in patients with relapsed or refractory acute lymphoblastic leukemia enrolled in INO-VATE. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Role of inotuzumab ozogamicin in the treatment of relapsed/refractory acute lymphoblastic leukemia. [2019]

10. Spain pubmed.ncbi.nlm.nih.gov

Inotuzumab ozogamicin for the treatment of patients with acute lymphocytic leukemia. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Inotuzumab ozogamicin for the treatment of acute lymphoblastic leukemia. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Inotuzumab ozogamicin in the treatment of B-cell acute lymphoblastic leukemia. [2022]