Inotuzumab Ozogamicin + Chemotherapy for Leukemia and Lymphoma

Recruiting in Palo Alto (17 mi)

+78 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Alliance for Clinical Trials in Oncology

Disqualifiers: Uncontrolled diabetes, cardiac, pulmonary, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment combining inotuzumab ozogamicin with chemotherapy for patients with certain types of blood cancer. The new drug targets cancer cells directly and delivers a toxin to kill them. This approach aims to improve the effectiveness of treatment compared to standard chemotherapy alone. Inotuzumab ozogamicin has shown superior efficacy compared to conventional chemotherapy in patients with specific types of blood cancer.

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.

What data supports the effectiveness of the drug Inotuzumab Ozogamicin combined with chemotherapy for leukemia and lymphoma?

Gemtuzumab ozogamicin, a similar drug to Inotuzumab Ozogamicin, has shown effectiveness in treating acute myeloid leukemia (AML) with overall response rates of about 30% in relapsed patients. It has been used in combination with chemotherapy and has shown potential in treating other CD33+ neoplastic diseases, indicating that similar antibody-targeted therapies can be effective in certain types of leukemia. ^{1 2 3 4 5}

What safety data exists for Inotuzumab Ozogamicin and Doxorubicin in humans?

Inotuzumab Ozogamicin has been associated with adverse effects like hyperbilirubinemia (high bilirubin levels), elevated liver enzymes, and sinusoidal obstruction syndrome (a liver condition). Doxorubicin, especially in its conventional form, can cause myelosuppression (reduced bone marrow activity), cardiotoxicity (heart damage), and other side effects, but liposomal formulations like Myocet may reduce these risks. ^{3 6 7 8 9}

What makes the drug Inotuzumab Ozogamicin unique for treating leukemia and lymphoma?

Inotuzumab Ozogamicin is unique because it is an antibody-drug conjugate that specifically targets CD22-expressing tumor cells, delivering a potent toxin directly to the cancer cells, which helps to minimize damage to healthy cells. This targeted approach is different from traditional chemotherapy, which affects both cancerous and healthy cells. ^{10 11 12 13 14}

Research Team

Marlise R. Luskin, MD, MSCE

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Doxorubicin (Anti-tumor antibiotic)
• Inotuzumab Ozogamicin (Monoclonal Antibodies)

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.

Participant Groups

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 Canada, Japan for the following indications:

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+

Suzanne George

Alliance for Clinical Trials in Oncology

Chief Medical Officer since 2015

MD from Harvard Medical School

Evanthia Galanis

Alliance for Clinical Trials in Oncology

Chief Executive Officer since 2022

MD from Mayo Clinic

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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 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]

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]

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]

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]

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]

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]

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, 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, 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 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]

References

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

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

2. England 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. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Pilot study of gemtuzumab ozogamicin, liposomal daunorubicin, cytarabine and cyclosporine regimen in patients with refractory acute myelogenous leukemia. [2019]

4. Turkey pubmed.ncbi.nlm.nih.gov

Use of gemtuzumab ozogamicin in the treatment of pediatric relapsed/ refractory Acute Myeloid Leukemia. [2016]

5. England pubmed.ncbi.nlm.nih.gov

The role of Gemtuzumab Ozogamicin in the treatment of acute myeloid leukemia patients. [2022]

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

Acute Left Ventricular Dysfunction Following Gemtuzumab Ozogamicin in Two Pediatric AML Patients. [2023]

7. United States 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. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Non-pegylated liposomal doxorubicin in lymphoma: patterns of toxicity and outcome in a large observational trial. [2018]

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

Electrosprayed Myocet-like Liposomes: An Alternative to Traditional Liposome Production. [2018]

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

Inotuzumab Ozogamicin: First Global Approval. [2019]

11. Spain pubmed.ncbi.nlm.nih.gov

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

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

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

13. 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]

14. England pubmed.ncbi.nlm.nih.gov

Inotuzumab ozogamicin, an anti-CD22-calecheamicin conjugate, for refractory and relapsed acute lymphocytic leukaemia: a phase 2 study. [2023]