Inotuzumab + Chemotherapy for Leukemia

(ALL-001 Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach for treating B-cell acute lymphoblastic leukemia (B-ALL) that has not responded to or has returned after initial treatment. The study examines whether adding inotuzumab ozogamicin (Besponsa) to standard chemotherapy regimens improves disease control. Participants will receive either a 3-drug or 4-drug regimen and will be monitored for treatment effects and overall survival. The trial seeks participants with relapsed or refractory B-ALL that is CD-22 positive and not associated with the Philadelphia chromosome. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that inotuzumab ozogamicin, the main treatment in this trial, has a noteworthy safety record. In past studies, 79.5% of patients experienced side effects during treatment, mostly related to blood issues. These results are relevant because they involved patients with a similar type of leukemia.

Another study found that inotuzumab ozogamicin is generally safe and well-tolerated by patients. While side effects are common, they can usually be managed. The FDA has also approved this treatment for other conditions, which adds confidence in its safety for humans.

This trial uses lower doses of inotuzumab ozogamicin, which might reduce the chance of side effects compared to standard doses. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about inotuzumab ozogamicin for leukemia because it offers a novel approach compared to standard chemotherapy regimens. Unlike traditional treatments that often rely on broad-spectrum chemotherapy agents, inotuzumab ozogamicin is an antibody-drug conjugate that specifically targets CD22-positive cancer cells, delivering a potent cytotoxic agent directly to the leukemia cells. This targeted mechanism can potentially reduce side effects by sparing healthy cells, an advantage over standard treatments like prednisone, vincristine, daunorubicin, and pegaspargase. Additionally, its ability to be combined with other drugs in either a 3-drug or 4-drug regimen offers flexible and potentially more effective treatment options for patients.

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

Research has shown that inotuzumab ozogamicin can help patients with relapsed or hard-to-treat B-cell acute lymphoblastic leukemia (B-ALL). In this trial, participants will receive either a 3-drug or a 4-drug re-induction regimen with inotuzumab ozogamicin. Studies have found that when combined with chemotherapy, inotuzumab ozogamicin enables many adult patients to achieve complete remission, meaning no signs of cancer are detected. Specifically, one study found that 74% of patients reached either complete remission or remission with some remaining symptoms. Additionally, 82% of these patients had very low levels of cancer cells left in their bodies. These encouraging results suggest that inotuzumab ozogamicin is a strong option for treating B-ALL. ^{1 3 5 6 7}

Who Is on the Research Team?

Michael Douvas, MD

Principal Investigator

University of Virginia

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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) 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]

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, 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 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]

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 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]

Citations

1. besponsa.pfizerpro.com besponsa.pfizerpro.com/efficacy/adult-clinical-data%E2%80%94ino-vate

BESPONSA® (inotuzumab ozogamicin) CR/CRi | Safety Info Efficacy and safety analysis by age cohort of inotuzumab ozogamicin in patients with relapsed or refractory acute lymphoblastic leukemia enrolled in INO-VATE.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12533514/

Inotuzumab ozogamicin in adult acute lymphoblastic leukemia Outcomes have been historically poor in adults with relapsed/refractory (R/R) B-cell ALL, with a 5-year overall survival (OS) rate of <10% with ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1422/531484/Safety-and-Efficacy-Results-of-Dose-Adjusted

Safety and Efficacy Results of Dose-Adjusted Inotuzumab ... Conclusions: The results of this study indicate that dose-adjusted InO is a well-tolerated and effective treatment option for B-ALL adults with ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12427359/

Real‐World Data on Inotuzumab Ozogamicin for Adult ... Complete remission or remission with incomplete recovery (CR/CRi) was achieved in 74% of patients. Among those evaluated, 82% reached MRD < 0.01 ...

5. haematologica.org haematologica.org/article/view/11921

Efficacy and safety of currently approved and lower starting ... This study evaluated efficacy and safety of the currently approved InO starting dose and a lower dose in adults with R/R ALL who were eligible for HSCT.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40120068/

INO-CD22: A multicenter, real-world study of inotuzumab ... Conclusions: Despite the limitations of retrospective studies, the INO-CD22 study highlights the favorable safety profile and clinical activity ...

7. 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.