Inotuzumab Ozogamicin + Chemotherapy for Leukemia and Lymphoma
Recruiting in Palo Alto (17 mi)
+70 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
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.
12345What 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.
36789What 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.
1011121314Eligibility 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.
+11 more
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.
+1 more
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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm A (inotuzumab ozogamicin, chemotherapy)Experimental Treatment10 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 Control10 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Siteman Cancer Center at Christian HospitalSaint Louis, MO
Billings Clinic Cancer CenterBillings, MT
Benefis Sletten Cancer InstituteGreat Falls, MT
Baptist Memorial Hospital and Cancer Center-MemphisMemphis, TN
More Trial Locations
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Who Is Running the Clinical Trial?
Alliance for Clinical Trials in OncologyLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Trials with gemtuzumab ozogamicin (Mylotarg) combined with chemotherapy regimens in acute myeloid leukemia. [2019]Gemtuzumab ozogamicin (Mylotarg) is an immunoconjugate composed of a recombinant humanized murine anti-CD33 antibody linked to calicheamicin, a potent cytotoxic agent. The aim of this review is to summarize ongoing trials with gemtuzumab ozogamicin in combination with chemotherapy in acute myeloid leukemia (AML) patients. The studies include determination of safety and efficacy of gemtuzumab ozogamicin in combination with chemotherapy in previously untreated as well as relapsed and refractory AML patients. These studies also determine gemtuzumab ozogamicin's activity in patients with other CD33+ neoplastic diseases such as myelodysplastic syndrome, acute promyelocytic leukemia, chronic myeloid leukemia, and certain subsets of acute lymphocytic leukemia. Moreover, trials are exploring the use of gemtuzumab ozogamicin with novel targeted agents such as Bcl-2 antisense molecules. Gemtuzumab ozogamicin is associated with an acceptable toxicity profile as a single agent; however, the incidence of veno-occlusive disease remains a concern with the use of gemtuzumab ozogamicin in combination with chemotherapy.
Efficacy and tolerability of gemtuzumab ozogamicin (anti-CD33 monoclonal antibody, CMA-676, Mylotarg) in children with relapsed/refractory myeloid leukemia. [2019]Gemtuzumab ozogamicin (GO) is a cytotoxic anti-CD33 monoclonal antibody that has given promising preliminary results in adult myeloid CD33+ AML. We conducted a retrospective multicenter study of 12 children treated with GO on a compassionate basis (median age 5.5 y). Three patients (2 MDS/AML, 1 JMML) were refractory to first-line treatment, 8 patients with de novo AML were in refractory first relapse, and one patient with de novo AML was in 2nd relapse after stem cell transplantation (SCT). CD33 expression exceeded 20% in all cases.
Pilot study of gemtuzumab ozogamicin, liposomal daunorubicin, cytarabine and cyclosporine regimen in patients with refractory acute myelogenous leukemia. [2019]Multi-drug resistance (MDR) protein expression is associated with reduced gemtuzumab ozogamicin (Mylotarg) activity. Both cyclosporine-A (CSA) and liposome-encapsulated daunorubicin, DaunoXome (DNX) may reduce the negative impact of MDR. A gemtuzumab ozogamicin, DNX, cytarabine (ara-C) and CSA (MDAC) regimen was piloted in patients with refractory acute myelogenous leukemia (AML) (relapsed 10, primary refractory 1) (median age 37 years (16-67)). One (9%) patient achieved a transient CR, one CRp. Grade 3/4 toxicities included sepsis (seven patients; 63%); hyperbilirubinemia (six patients; 54%), with transaminitis in one patient; mucositis (three patients; 27%). The inclusion of CSA in a gemtuzumab ozogamicin-containing regimen is feasible. The MDAC regimen was associated with significant toxicity in a cohort of patients with very advanced AML.
Use of gemtuzumab ozogamicin in the treatment of pediatric relapsed/ refractory Acute Myeloid Leukemia. [2016]Gemtuzumab ozogamicin (GO, MylotargTM) is an antibody-targeted chemotherapy agent that has been studied in acute myeloid leukemia (AML) at first relapse in adults. There is limited experience in pediatric patients. We report six patients with refractory/relapsed CD33+AML who were treated with GO on compassionate-use basis. One patient attained remission. One patient is still alive following hematopoietic stem cell transplantation (HSCT), and one patient died in remission. Two patients were refractory and three patients had a response with
The role of Gemtuzumab Ozogamicin in the treatment of acute myeloid leukemia patients. [2022]Gemtuzumab Ozogamicin (GO) is an antibody-targeted chemotherapy agent consisting of the humanized murine CD33 antibody (clone P67.6) to which the calicheamicin-g1 derivative is attached via a hydrolysable bifunctional linker. GO is able to induce apoptosis in vitro in CD33-expressing cells and it has been approved in USA and in Europe as monotherapy for the treatment of elderly patients (older than 60 years) with relapsed acute myeloid leukemia (AML). GO administered as a single agent has resulted in overall response rates of about 30% in previously relapsed adults AML patients (including also with incomplete platelet recovery). Preliminary data indicate a potential role for GO also as a component of induction or consolidation regimens in adults and children. As for adverse events, veno-occlusive syndrome characterizes its tolerability profile, but GO is comparatively well tolerated by most patients.
Acute Left Ventricular Dysfunction Following Gemtuzumab Ozogamicin in Two Pediatric AML Patients. [2023]Gemtuzumab ozogamicin (GO) is an anti-CD33 antibody-tumor antibiotic conjugate with proven efficacy in pediatric and adult patients with CD33+ acute myeloid leukemia. Adverse effects commonly associated with GO include hyperbilirubinemia, elevated transaminases, and sinusoidal obstruction syndrome. Cardiotoxicity has not been a commonly described adverse event. We describe 2 pediatric patients with relapsed/refractory acute myeloid leukemia who received fractionated GO monotherapy and subsequently developed severe acute left ventricular dysfunction. Both patients achieved remission, recovered cardiac function with medical therapy, and tolerated subsequent stem cell transplantation.
Comparison of the adverse event profiles of conventional and liposomal formulations of doxorubicin using the FDA adverse event reporting system. [2022]Doxorubicin (DOX) is an anthracycline widely used for the treatment of solid and hematological tumors. The aim of this study was to assess the adverse event profiles of conventional DOX and liposomal DOX. This is the first study to evaluate the effect of a liposomal formulation of DOX using spontaneous reporting system (SRS) databases. The SRS used was the US Food and Drug Administration Adverse Event Reporting System (FAERS). This study relied on definitions of preferred terms provided by the Medical Dictionary for Regulatory Activities (MedDRA) and the standardized MedDRA Queries (SMQ) database. We also calculated the reporting odds ratios (RORs) of suspected drugs (conventional DOX; PEGylated-liposome DOX; non-PEGylated-liposome DOX). The FAERS database contained 7,561,254 reports from January 2004 to December 2015. The number of reported AE cases for conventional DOX, PEGylated-liposome DOX, and non-PEGylated-liposome DOX was 5039, 3780, and 349, respectively. Conventional DOX and liposomal DOX have potential risks of causing myelosuppression, cardiotoxicity, alopecia, nausea, and vomiting, among other effects. The RORs (95% CI) from SMQ for haematopoietic leucopenia associated with conventional DOX, PEGylated-liposome DOX, and non-PEGylated-liposome DOX were 12.75 (11.89-13.68), 6.43 (5.81-7.13), and 14.73 (11.42-18.99), respectively. Liposomal DOX formulations were associated with lower RORs with regard to myelosuppression, cardiotoxicity, and alopecia than the conventional DOX was. The RORs (95% CI) for palmar-plantar erythrodysesthesia (PPE) associated with conventional DOX, PEGylated-liposome DOX, and non-PEGylated-liposome DOX were 6.56 (4.74-9.07), 64.77 (56.84-73.80), and 28.76 (15.77-52.45), respectively. This study is the first to evaluate the relationship between DOX liposomal formulations and their adverse event profiles. The results indicate that careful observation for PPE is recommended with the use of liposomal DOX, especially PEGylated-liposome DOX formulations.
Non-pegylated liposomal doxorubicin in lymphoma: patterns of toxicity and outcome in a large observational trial. [2018]The anthracycline doxorubicin plays a major role in the treatment of lymphoproliferative disorders. However, its use is often limited due to cardiac toxicity, which seems to be much less in the liposomal non-pegylated formulation (Myocet®). The aim of this study was the evaluation of efficacy and toxicity of Myocet®-containing treatment regimens, with a focus on cardiotoxicity during treatment in lymphoma patients. A total of 326 consecutive patients, treated between March 2008 and December 2013 in 11 Austrian and 1 Italian cancer centers, were retrospectively assessed. Patients' baseline and treatment-related parameters were obtained by reviewing hospital records. Median age was 74 years (range 26-93). The most common histology was DLBCL (60 %), followed by FL (13 %) and MCL (8 %). At least one cardiovascular comorbidity was present in 72 % of patients. Most common grade 3/4 toxicities were hematologic, namely, leukopenia, neutropenia, thrombocytopenia, and febrile neutropenia in 44, 40, 17, and 16 %. Overall, 43 patients suffered a cardiac event (any grade) with most patients developing congestive heart failure. Parameters significantly associated with severe cardiac events (grades 3-5) were the presence of cardiovascular comorbidities, chronic obstructive pulmonary disease, and elevated baseline NT-proBNP. Treatment response after first line Myocet®-containing therapy was ≥58 % among all entities (range 58-86 %) and therefore comparable to those of conventional therapeutic regimens. Herein, we provide a detailed toxicity profile of Myocet®-containing chemotherapy regimens. Despite the high rate of patients with preexisting comorbidities, the number of adverse events was encouraging. However, these results need to be confirmed in a prospective randomized trial.
Electrosprayed Myocet-like Liposomes: An Alternative to Traditional Liposome Production. [2018]Although doxorubicin (DXR) has been on the market for many years as an anti-cancer drug, a number of serious dose-limiting toxicities hinder its widespread use. To reduce the known toxicities of soluble DXR, various liposomes have been designed including Doxil, Caelyx, and Myocet. Myocet, a non-PEGylated liposomal formulation containing DXR, was found to reduce the toxicities associated with soluble DXR and has been used in Europe and Canada (but not the US) as a first line therapy. While regarded as successful, Myocet does have some formulation drawbacks including stability, drug release, and an arduous formulation and remote loading method for preparation.
Inotuzumab Ozogamicin: First Global Approval. [2019]Intravenous inotuzumab ozogamicin (Besponsa®; Pfizer) is an anti-CD22 monoclonal antibody-calicheamicin conjugate that binds to CD22-expressing tumour cells. Upon binding, the complex is internalised and the cytotoxic calicheamicin derivative is released inside the cell, inducing double-strand DNA breakage and subsequent cell death. In June 2017, the EMA granted inotuzumab ozogamicin approval as monotherapy for the treatment of adults with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukaemia (ALL). The use of inotuzumab ozogamicin in adult patients with Philadelphia chromosome-positive, relapsed or refractory CD22-positive B-cell precursor ALL is restricted to those who have failed treatment with at least one tyrosine kinase inhibitor. Inotuzumab ozogamicin was granted priority review for the treatment of relapsed or refractory B-cell precursor ALL by the US FDA in February 2017. In the USA, a phase III trial evaluating inotuzumab ozogamicin in combination with frontline chemotherapy in adults with newly diagnosed B-cell ALL has recently been initiated and inotuzumab ozogamicin is under phase II evaluation in childhood CD22-positive B-cell ALL. Inotuzumab ozogamicin combination therapies are also being evaluated in the phase I/II or II setting in ALL and chronic myeloid leukaemia and in the phase I setting in Burkitt's lymphoma. This article summarises the milestones in the development of inotuzumab ozogamicin leading to this first approval for ALL.
Inotuzumab ozogamicin for the treatment of patients with acute lymphocytic leukemia. [2019]Inotuzumab ozogamicin is an antibody-drug conjugate comprised of a humanized anti-CD22 monoclonal antibody conjugated to calicheamicin, a cytotoxic antibiotic agent. Inotuzumab ozogamicin binds to CD22-expressing tumor cells, resulting in apoptotic cell death. Based on the results of the pivotal, phase III INO-VATE trial in acute lymphoblastic leukemia (ALL), approval of inotuzumab ozogamicin was recently granted for the treatment of patients with relapsed or refractory ALL, a group that otherwise has a poor prognosis with standard chemotherapy. Several ongoing clinical trials are now testing whether outcomes can be further improved by combining inotuzumab ozogamicin with low-dose chemotherapy or by including inotuzumab ozogamicin in the front-line setting. In this article we discuss the preclinical, clinical and safety data of inotuzumab ozogamicin.
Role of inotuzumab ozogamicin in the treatment of relapsed/refractory acute lymphoblastic leukemia. [2019]Inotuzumab ozogamicin is a humanized anti-CD22 monoclonal antibody bound to a toxic natural calicheamicin, which is under investigation for the treatment of relapsed/refractory acute lymphoblastic leukemia. CD22 is commonly expressed in 90-100% of malignant mature B-lymphocyte lineage. The first Phase II study with inotuzumab ozogamicin conducted by Kantarjian et al. gave the opportunity for heavily pretreated patients with acute lymphoblastic leukemia to go for allogeneic stem cell transplant. Inotuzumab is well-tolerated with the exception of veno-occlusive disease. Overall inotuzumab ozogamicin is potentially an encouraging and promising therapy for patients.
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.
Inotuzumab ozogamicin, an anti-CD22-calecheamicin conjugate, for refractory and relapsed acute lymphocytic leukaemia: a phase 2 study. [2023]The outlook for patients with refractory and relapsed acute lymphocytic leukaemia (ALL) is poor. CD22 is highly expressed in patients with ALL. Inotuzumab ozogamicin is a CD22 monoclonal antibody conjugated to the toxin calecheamicin. We did a phase 2 study to assess the efficacy of this antibody.