Inotuzumab Ozogamicin + Chemotherapy for Leukemia and Lymphoma

Not currently recruiting at 82 trial locations

Overseen By Marlise R. Luskin, MD, MSCE

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alliance for Clinical Trials in Oncology

Disqualifiers: Uncontrolled diabetes, cardiac, pulmonary, 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

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with B-cell acute lymphoblastic leukemia or B-cell lymphoblastic lymphoma, two types of blood cancers. The researchers aim to determine if adding a new drug, inotuzumab ozogamicin, to standard chemotherapy can more effectively shrink the cancer and prevent its return. Inotuzumab ozogamicin is a targeted therapy that specifically attacks cancer cells. This trial suits those diagnosed with these specific blood cancers who have not undergone extensive chemotherapy but experience active symptoms affecting daily life. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that patients being treated with chronic steroids for other reasons are eligible, suggesting some medications may be allowed. It's best to discuss your specific medications with the trial team.

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

Research has shown that inotuzumab ozogamicin is usually well-tolerated. Studies have found it can effectively treat certain types of leukemia and lymphoma with few side effects. However, it may cause serious issues, such as liver problems, including a rare but serious condition called VOD, as well as infections and bleeding. Most side effects can be managed, but some can be serious.

Doxorubicin, a common chemotherapy drug, works well but can also have side effects. These may include heart problems and a decrease in blood cell counts, which can lead to infections or bleeding.

Both treatments have been used in various situations, providing some reassurance about their safety. However, participants should discuss potential risks with their doctors before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about inotuzumab ozogamicin for leukemia and lymphoma because it targets cancer cells in a unique way. Unlike traditional chemotherapy, which affects both healthy and cancerous cells, inotuzumab ozogamicin is an antibody-drug conjugate that specifically binds to CD22, a protein found on the surface of cancer cells, delivering a potent toxin directly to them. This targeted approach aims to reduce side effects and improve the effectiveness of treatment. Additionally, combining this drug with standard chemotherapy could enhance outcomes by attacking the cancer from multiple angles.

What evidence suggests that this trial's treatments could be effective for leukemia and lymphoma?

Research shows that inotuzumab ozogamicin may help treat certain types of blood cancer, specifically B-cell acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL). Studies have found it effective for patients whose ALL has returned or hasn't responded to other treatments. One study noted that 84% of patients experienced a reduction or disappearance of their cancer. In this trial, some participants will receive inotuzumab ozogamicin alongside chemotherapy, which might enhance its effectiveness and potentially lead to better results. Meanwhile, other participants will receive chemotherapy alone, allowing for a comparison of outcomes between the two approaches. ^{1 2 3 6 7}

Who Is on the Research Team?

Marlise R. Luskin, MD, MSCE

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

Adults aged 50 or older with B-cell acute lymphoblastic leukemia or B-cell lymphoblastic lymphoma can join this trial. They must have certain levels of cancer cells in their blood/marrow, be CD22 positive, and not have had much prior treatment for ALL. Good kidney/liver function and a decent performance status are required. Those with active hepatitis C/B virus infections under control may qualify but must use birth control due to the risks from therapy.

Inclusion Criteria

Creatinine =< 2.0 g/dL

I had hepatitis C but it's cleared and my liver is healthy.

I am 50 years old or older.

Exclusion Criteria

I have symptoms from my brain or spinal cord disease.

I do not have uncontrolled diabetes, heart, or lung disease.

I have another active cancer besides the one being treated.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive induction therapy with chemotherapy and inotuzumab ozogamicin for up to 8 cycles, depending on age and response.

8 months

Multiple visits per cycle

Maintenance

Patients receive maintenance therapy with vincristine, prednisone, mercaptopurine, and methotrexate for up to 24 cycles or 2 years.

2 years

Monthly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

5 years

Every 2 months for 1 year, every 3 months for 2 years, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Doxorubicin
• Inotuzumab Ozogamicin

Trial Overview The study is testing if adding Inotuzumab Ozogamicin (a targeted antibody-drug conjugate) to lower-dose chemotherapy is more effective than usual chemotherapy alone for treating these cancers. The goal is to see if this combination can better shrink the cancer and prevent it from coming back.

How Is the Trial Designed?

Group I: Arm A (inotuzumab ozogamicin, chemotherapy) Experimental Treatment 10 Interventions

Induction: For cycles 1-4 on days 2 and 8, patients receive inotuzumab ozogamicin IV and IT chemotherapy consisting of alternating Cytarabine and Methotrexate. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8 of cycles 1-4. For cycles 1,3,5,7, patients receive cyclophosphamide intravenously (IV) on days 1-3, mesna IV, vincristine IV on days 1 and 8, and dexamethasone IV or orally (PO) on days 1-4 and 11-14. For cycles 2,4,6,8, patients receive methotrexate on day 1, cytarabine IV on days 2-3, and methylprednisolone on days 1-3. Patients \>= 70 years of age receive either 2 or 4 cycles of treatment. Patients \< 70 years of age receive up to 8 cycles of treatment. Maintenance: Patients receive vincristine IV on day 1, prednisone PO on days 1-5, mercaptopurine PO on days 1-28, and methotrexate PO weekly. Treatment occurs for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity.

Group II: Arm B (chemotherapy) Active Control 10 Interventions

Induction: For cycles 1-4 on days 2 and 8, patients receive IT chemotherapy consisting of alternating Cytarabine and Methotrexate. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8 of cycles 1-4. For cycles 1,3,5,7, patients receive cyclophosphamide intravenously (IV) on days 1-3, mesna IV, doxorubicin IV on day 4, vincristine IV on days 1 and 8, and dexamethasone IV or orally (PO) on days 1-4 and 11-14. For cycles 2,4,6,8, patients receive methotrexate on day 1, cytarabine IV on days 2-3, and methylprednisolone on days 1-3. Patients \>= 70 years of age receive either 2 or 4 cycles of treatment. Patients \< 70 years of age receive up to 8 cycles of treatment. Maintenance: Patients receive vincristine IV on day 1, prednisone PO on days 1-5, mercaptopurine PO on days 1-28, and methotrexate PO weekly. Treatment occurs for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity.

Doxorubicin is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Adriamycin for:

• Breast cancer
• Ovarian cancer
• Bladder cancer
• Lymphomas
• Leukemias
• Multiple myeloma
• Kaposi's sarcoma
• Soft tissue sarcomas

Approved in European Union as Doxorubicin for:

• Breast cancer
• Ovarian cancer
• Bladder cancer
• Lymphomas
• Leukemias
• Multiple myeloma
• Kaposi's sarcoma
• Soft tissue sarcomas

Approved in Canada as Doxorubicin for:

• Breast cancer
• Ovarian cancer
• Bladder cancer
• Lymphomas
• Leukemias
• Multiple myeloma
• Kaposi's sarcoma
• Soft tissue sarcomas

Approved in Japan as Doxorubicin for:

• Breast cancer
• Ovarian cancer
• Bladder cancer
• Lymphomas
• Leukemias
• Multiple myeloma
• Kaposi's sarcoma
• Soft tissue sarcomas

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

The pilot study of the MDAC regimen (gemtuzumab ozogamicin, DaunoXome, cytarabine, and cyclosporine-A) in 8 patients with refractory acute myelogenous leukemia showed that the inclusion of cyclosporine-A is feasible, potentially helping to counteract multi-drug resistance.

However, the regimen was associated with significant toxicities, including high rates of sepsis (63%) and hyperbilirubinemia (54%), indicating that while the treatment may be viable, it carries considerable risks for patients with advanced AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of gemtuzumab ozogamicin, liposomal daunorubicin, cytarabine and cyclosporine regimen in patients with refractory acute myelogenous leukemia. Apostolidou, E., Cortes, J., Tsimberidou, A., et al.[2019]

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]

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, a CD22-targeted therapy, demonstrated a 57% overall response rate in patients with refractory and relapsed acute lymphocytic leukaemia (ALL), indicating its potential efficacy in this challenging patient population.

The treatment was associated with manageable adverse effects, including fever and liver-related toxicities, suggesting that while it is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inotuzumab ozogamicin, an anti-CD22-calecheamicin conjugate, for refractory and relapsed acute lymphocytic leukaemia: a phase 2 study. Kantarjian, H., Thomas, D., Jorgensen, J., et al.[2023]

Gemtuzumab ozogamicin (GO) is effective in treating pediatric patients with relapsed/refractory acute myeloid leukemia, as demonstrated by the two cases where patients achieved remission after treatment.

Despite its efficacy, GO can lead to severe acute left ventricular dysfunction, highlighting the need for monitoring cardiac function during treatment, although both patients recovered with medical therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Left Ventricular Dysfunction Following Gemtuzumab Ozogamicin in Two Pediatric AML Patients. McNerney, KO., Oranges, K., Seif, AE., et al.[2023]

This study analyzed over 7.5 million reports from the FDA Adverse Event Reporting System and found that conventional doxorubicin (DOX) has a higher incidence of adverse events compared to liposomal formulations, particularly in terms of myelosuppression and cardiotoxicity.

Liposomal DOX, especially the PEGylated version, showed lower reporting odds ratios for serious side effects like myelosuppression and cardiotoxicity, but a higher risk for palmar-plantar erythrodysesthesia (PPE), indicating the need for careful monitoring when using these formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the adverse event profiles of conventional and liposomal formulations of doxorubicin using the FDA adverse event reporting system. Fukuda, A., Tahara, K., Hane, Y., et al.[2022]

In a study of 326 lymphoma patients treated with Myocet® (a liposomal formulation of doxorubicin), the treatment showed a comparable response rate of at least 58% to conventional therapies, indicating its efficacy in managing lymphoproliferative disorders.

Despite a high prevalence of cardiovascular comorbidities (72% of patients), the incidence of severe cardiac events was relatively low, suggesting that Myocet® may have a better safety profile regarding cardiotoxicity compared to traditional doxorubicin formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-pegylated liposomal doxorubicin in lymphoma: patterns of toxicity and outcome in a large observational trial. Wasle, I., Gamerith, G., Kocher, F., et al.[2018]

Electrospray manufacturing of Myocet-like liposomes allows for a more efficient and scalable production process, enhancing drug retention and stability compared to traditional thin-film hydration methods.

The electrosprayed liposomes demonstrated similar drug loading and cytotoxicity profiles to conventional formulations, but with significantly prolonged release kinetics, potentially improving therapeutic outcomes for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrosprayed Myocet-like Liposomes: An Alternative to Traditional Liposome Production. Collier, MA., Bachelder, EM., Ainslie, KM.[2018]

In a retrospective study of 12 children with myeloid CD33+ AML, Gemtuzumab ozogamicin (GO) showed a 25% complete response rate, leading to further curative treatment in three patients, indicating potential efficacy in this population.

The treatment was associated with significant hematological toxicity and some adverse events, but no major complications like sinusoidal obstruction syndrome were reported, suggesting a need for careful monitoring in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of gemtuzumab ozogamicin (anti-CD33 monoclonal antibody, CMA-676, Mylotarg) in children with relapsed/refractory myeloid leukemia. Brethon, B., Auvrignon, A., Galambrun, C., et al.[2019]

Gemtuzumab Ozogamicin (GO) is an effective targeted chemotherapy for elderly patients with relapsed acute myeloid leukemia (AML), achieving an overall response rate of about 30% in this population.

While GO can cause veno-occlusive syndrome, it is generally well tolerated by most patients, making it a viable treatment option for those over 60 years old.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of Gemtuzumab Ozogamicin in the treatment of acute myeloid leukemia patients. Pagano, L., Fianchi, L., Caira, M., et al.[2022]

Inotuzumab ozogamicin is an effective treatment for adults with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukaemia (ALL), approved by the EMA in June 2017, and works by delivering a cytotoxic agent directly into cancer cells, leading to their death.

The drug is specifically indicated for patients who have not responded to at least one tyrosine kinase inhibitor, and ongoing trials are exploring its use in combination with chemotherapy for newly diagnosed B-cell ALL and in other types of leukaemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inotuzumab Ozogamicin: First Global Approval. Lamb, YN.[2019]

Gemtuzumab ozogamicin (Mylotarg) is being studied in ongoing trials for its safety and efficacy in treating acute myeloid leukemia (AML) patients, both newly diagnosed and those with relapsed or refractory disease.

While gemtuzumab ozogamicin shows an acceptable toxicity profile as a standalone treatment, there is a notable risk of veno-occlusive disease when used in combination with chemotherapy, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trials with gemtuzumab ozogamicin (Mylotarg) combined with chemotherapy regimens in acute myeloid leukemia. Stadtmauer, EA.[2019]

In a compassionate-use study of six pediatric patients with refractory/relapsed CD33+ acute myeloid leukemia (AML) treated with gemtuzumab ozogamicin (GO), one patient achieved remission and another is alive after hematopoietic stem cell transplantation, indicating some potential efficacy in this population.

However, the treatment was associated with significant side effects, including a high incidence of veno-occlusive disease (VOD) in three patients, suggesting that GO should be used with caution in pediatric patients due to these serious complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of gemtuzumab ozogamicin in the treatment of pediatric relapsed/ refractory Acute Myeloid Leukemia. Ünal, E., Sahdev, I.[2016]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33461955/

Efficacy and Safety of Inotuzumab Ozogamicin (CMC-544) ... Conclusions: According to our study, INO was effective in the treatment of relapsed/refractory ALL and NHL with limited adverse effects. High-quality randomized ...

2. 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.

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. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265020310144

Efficacy and Safety of Inotuzumab Ozogamicin (CMC-544) ... Over the past 40 years, outcomes for newly diagnosed patients with ALL and NHL have improved dramatically, with 5-year overall survival rates rising to nearly ...

5. aetna.com aetna.com/cpb/medical/data/900_999/0919.html?ref=counterforcehealth.org

Inotuzumab Ozogamicin (Besponsa) - Medical Clinical ... Among patients receiving the MTD (n = 38), the overall response rate (ORR) was 84 % (n = 32), including 24 % (n = 9) with CR; the ORR was 100 % for patients ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT00717925

NCT00717925 | Study Evaluating Safety and Tolerability of ... To assess the tolerability and the initial safety profile of Inotuzumab Ozogamicin (CMC-544) in patients with B-Cell Non-Hodgkin's Lymphoma (NHL). Official ...

7. besponsa.pfizerpro.com besponsa.pfizerpro.com/safety/adult-safety-data

BESPONSA® (inotuzumab ozogamicin) Safety Information BESPONSA has a BOXED WARNING for VOD and post-HSCT NRM · The most common (≥2%) serious adverse reactions (ARs) were infection, febrile neutropenia, hemorrhage, ...