Gemtuzumab Ozogamicin for Acute Myeloid Leukemia
Recruiting in Palo Alto (17 mi)
+1 other location
Overseen byMary-Elizabeth Percival
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Washington
Must not be taking: Investigational agents
Disqualifiers: Chemotherapy, Radiation, Uncontrolled illness, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?This phase II trial studies the how well fractionated gemtuzumab ozogamicin works in treating measurable residual disease in patients with acute myeloid leukemia. Gemtuzumab ozogamicin is a monoclonal antibody, called gemtuzumab, linked to a chemotherapy drug, called ozogamicin. Gemtuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD33 receptors, and delivers a chemotherapy known as calicheamicin to kill them.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, you cannot have had chemotherapy or radiation therapy within 14 days before starting the study, and you cannot be on other investigational drugs.
What data supports the effectiveness of the drug Gemtuzumab Ozogamicin (Mylotarg) for treating acute myeloid leukemia?
Research shows that Gemtuzumab Ozogamicin can lead to complete remission (when cancer symptoms disappear) or partial remission in about 25% of adults with a specific type of leukemia (CD33-positive AML) who have relapsed. It is especially useful for patients over 60 who cannot undergo other chemotherapy treatments.
12345Is Gemtuzumab Ozogamicin safe for humans?
Gemtuzumab Ozogamicin, also known as Mylotarg, has been associated with some serious side effects, including liver problems and a condition called veno-occlusive disease (a liver condition that can block blood flow). However, it is generally well tolerated by most patients, and its safety has been supported by various studies, leading to its approval for certain types of leukemia.
13567What makes the drug Gemtuzumab Ozogamicin unique for treating acute myeloid leukemia?
Gemtuzumab Ozogamicin is unique because it combines a monoclonal antibody with a powerful cancer-killing agent, specifically targeting the CD33 protein found on leukemia cells. This targeted approach allows it to be used in patients who are not eligible for other chemotherapy options, especially those over 60 years old with relapsed acute myeloid leukemia.
13489Eligibility Criteria
This trial is for people aged 2 and older with Acute Myeloid Leukemia (AML) who have already had at least one round of standard chemo. They must show minimal remaining disease, be in good enough health to perform daily activities, and not have certain types of AML like APL. Pregnant women can't join, and those able to conceive must test negative for pregnancy.Inclusion Criteria
My bilirubin levels are within twice the normal range, or I have Gilbert's disease.
My child's bilirubin levels are within the normal range for their age, or they have Gilbert's disease.
My kidney function is good, with a creatinine level of 2.0 mg/dL or less.
+12 more
Exclusion Criteria
I have not had chemotherapy or radiation in the last 14 days.
Subjects may not be receiving other investigational agents.
I do not have any severe illnesses that would stop me from following the study's requirements.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Patients receive gemtuzumab ozogamicin intravenously on days 1, 4, 7. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.
5 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
6 months
Participant Groups
The trial tests fractionated Gemtuzumab Ozogamicin (GO), a targeted antibody-chemo combo that seeks out cancer cells by attaching to CD33 receptors on their surface. It's given to patients whose AML isn't fully gone after treatment but is low ('measurable residual disease').
1Treatment groups
Experimental Treatment
Group I: Treatment (gemtuzumab ozogamicin)Experimental Treatment2 Interventions
Patients receive gemtuzumab ozogamicin IV on days 1, 4, 7. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity. Responders and non-responders, without significant adverse events during the first course, may receive a second course of gemtuzumab ozogamicin within 60 days after course 1.
Gemtuzumab Ozogamicin is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Mylotarg for:
- Acute myeloid leukemia (AML)
🇪🇺 Approved in European Union as Mylotarg for:
- Acute myeloid leukemia (AML)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, WA
Fred Hutchinson Cancer Center/University of Washington Cancer ConsortiumSeattle, WA
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Who Is Running the Clinical Trial?
University of WashingtonLead Sponsor
PfizerIndustry Sponsor
References
Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. [2022]Three open-label, multicenter trials were conducted to evaluate the efficacy and safety of single-agent Mylotarg (gemtuzumab ozogamicin; CMA-676; Wyeth Laboratories, Philadelphia, PA), an antibody-targeted chemotherapy agent, in patients with CD33-positive acute myeloid leukemia (AML) in untreated first relapse.
Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence. [2022]In this study, the authors analyzed the efficacy and safety of gemtuzumab ozogamicin (GO) (Mylotarg), an antibody-targeted chemotherapy for CD33-positive acute myeloid leukemia (AML).
Gemtuzumab ozogamicin: a review of its use in acute myeloid leukaemia. [2022]Gemtuzumab ozogamicin (Mylotarg) is a conjugate of a monoclonal antibody and calicheamicin, which targets the membrane antigen CD33 in CD33-positive acute myeloid leukaemia (AML) and, after cell internalisation, releases a derivative of the cytotoxic calicheamicin component. In the US, it is approved as monotherapy in patients aged > or =60 years with a first relapse of AML who are ineligible for other cytotoxic therapy. Monotherapy with gemtuzumab ozogamicin results in complete remission (CR) or CR with incomplete platelet recovery (CRp) in approximately =25% of adults (including those aged > or =60 years) with CD33-positive AML in first relapse. Preliminary data indicate a potential role for gemtuzumab ozogamicin as a component of induction or consolidation regimens in adults and, based on an early study, in the treatment of children with AML, although randomised, controlled studies are needed. Serious adverse events, notably hepatotoxicity, characterise its tolerability profile, but gemtuzumab ozogamicin is comparatively well tolerated by most patients. Gemtuzumab ozogamicin is a valuable new treatment option for patients aged > or =60 years with CD33-positive AML in first relapse for whom other cytotoxic chemotherapy is not considered appropriate; patients with a first CR (CR1) of >12 months are likely to have the best outcome.
Spotlight on gemtuzumab ozogamicin in acute myeloid leukaemia. [2018]Gemtuzumab ozogamicin (Mylotarg) is a conjugate of a monoclonal antibody and calicheamicin, which targets the membrane antigen CD33 in CD33-positive acute myeloid leukaemia (AML) and, after cell internalization, releases a derivative of the cytotoxic calicheamicin component. In the US, it is approved as monotherapy in patients aged>or=60 years with a first relapse of AML who are ineligible for other cytotoxic therapy. Monotherapy with gemtuzumab ozogamicin results in complete remission (CR) or CR with incomplete platelet recovery (CRp) in approximate, equals 25% of adults (including those aged>or=60 years) with CD33-positive AML in first relapse. Preliminary data indicate a potential role for gemtuzumab ozogamicin as a component of induction or consolidation regimens in adults and, based on an early study, in the treatment of children with AML, although randomized, controlled studies are needed. Serious adverse events, notably hepatotoxicity, characterize its tolerability profile, but gemtuzumab ozogamicin is comparatively well tolerated by most patients. Gemtuzumab ozogamicin is a valuable new treatment option for patients aged>or=60 years with CD33-positive AML in first relapse for whom other cytotoxic chemotherapy is not considered appropriate; patients with a first CR (CR1) of >12 months are likely to have the best outcome.
Pharmacokinetic/Pharmacodynamic Modeling to Support the Re-approval of Gemtuzumab Ozogamicin. [2020]Gemtuzumab ozogamicin (Mylotarg; Pfizer, New York, NY) was the first antibody-drug conjugate to be approved for CD33-positive acute myeloid leukemia (AML). However, it was voluntarily withdrawn from the US market due to lack of clinical benefit in the confirmatory phase III trial. In 2012, several investigator cooperative studies using a different dosing regimen showed efficacy, but pharmacokinetic (PK) data were not collected in these trials. Through simulation of expected concentrations for new dosing regimens, PK/pharmacodynamic modeling was able to support the safety and efficacy of these regimens. Significant exposure-response relationships were found for the attainment of complete remission with and without platelet recovery, attainment of blast-free status, the time course of myelosuppression, several grade ≥ 3 hepatic adverse events, and veno-occlusive disease. Gemtuzumab ozogamicin received full approval by the US Food and Drug Administration (FDA) in September 2017 for newly diagnosed and relapsed AML in adult patients and relapsed AML in pediatric patients aged 2-17 years.
Early phase I/II trials with gemtuzumab ozogamicin (Mylotarg) in acute myeloid leukemia. [2019]Relapsed acute myeloid leukemia (AML) carries a poor prognosis. Treatment options are limited, and their toxicities are substantial. There is an urgent need for novel therapies that are effective and have acceptable side effects. Gemtuzumab ozogamicin (Mylotarg) is an immunoconjugate targeted against CD33, which is expressed on more than 90% of myeloid leukemic blasts. The antibody is attached to calicheamicin, a potent cytotoxic enediyne antibiotic that inhibits DNA synthesis and induces apoptosis. In vitro studies showed excellent activity of gemtuzumab ozogamicin in leukemic cell lines and encouraged the evaluation of this agent in patients. In this review, early phase I/II studies that led to the US Food and Drug Administration approval of this immunoconjugate for older patients with relapsed AML are discussed. Potential adverse events reported with this agent, particularly the recent data of possible veno-occlusive disease and increased hepatotoxicity, are addressed. This agent is currently being investigated in many clinical trials as a front-line approach in previously untreated individuals, and it is likely that it will have many more indications in the near future.
Nursing implications of mylotarg: a novel antibody-targeted chemotherapy for CD33+ acute myeloid leukemia in first relapse. [2012]To review the nursing implications of gemtuzumab ozogamicin (Mylotarg(r), CMA-676, Wyeth Pharmaceuticals, Philadelphia, PA), a novel monoclonal antibody-targeted chemotherapy agent for relapsed acute myeloid leukemia (AML).
Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia. [2022]Gemtuzumab ozogamicin (Mylotarg; Wyeth Laboratories, Philadelphia, PA) consists of a semisynthetic derivative of calicheamicin, a cytotoxic antibiotic linked to a recombinant monoclonal antibody directed against the CD33 antigen present on leukemic myeloblasts in most patients with acute myeloid leukemia (AML). In this study, we review the preclinical and clinical profiles of this immunoconjugate and the regulatory review that led to marketing approval by the United States Food and Drug Administration.
Gemtuzumab ozogamicin in the treatment of acute myeloid leukemia. [2019]Options for treatment of poor-prognosis or relapsed acute myeloid leukemia (AML) remain limited. Gemtuzumab ozogamicin (Mylotarg, Wyeth-Ayerst, Philadelphia, PA) is an immunoconjugate composed of recombinant humanized murine anti-CD33 antibody linked to calicheamicin, a potent cytotoxic agent. Phase II trials have shown the efficacy of gemtuzumab ozogamicin in the treatment of relapsed AML. Trials exploring this agent in other CD33+ hematologic malignancies and in combination with other agents for AML are ongoing. Gemtuzumab ozogamicin is associated with acceptable toxicity as a single agent. However, the incidence of veno-occlusive disease of the liver remains a concern when this agent is used in combination with chemotherapy or in the context of hematopoietic stem cell transplant.