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Label indication MYLOTARG is a CD33-directed antibody and cytotoxic drug conjugate indicated for: • treatment of newly-diagnosed CD33-positive acute myeloid leukemia (AML) in adults and pediatric patients 1 month and older ( 1.1 ). • treatment of relapsed or refractory CD33-positive AML in adults and pediatric patients 2 years and older ( 1.2 ). FDA label
Also known as Mylotarg (gemtuzumab ozogamicin) Injection, Gemtuzumab Ozogamicin, Gemtuzumab Ozogamicin (GO)
Mylotarg · 8 trials · 5 indications
The primary analysis will be carried out once the last patient has a minimum of 1 year follow up. EFS estimates will be presented at 24 months along with 95% confidence intervals.
The primary analysis will be carried out once the last patient has a minimum of 1 year follow up. RFS estimates will be presented at 24 months along with 95% confidence intervals.
Early treatment related adverse reactions defined as the incidence by day 100 post-transplant of grade 3-5 toxicity for the following systems using the National Cancer Institute (NCI) Common Terminology Criteria v4: * Cardiac (pericardial effusion/Left ventricular systolic dysfunction). * Respiratory, thoracic and mediastinal (hypoxia/pneumonitis). * Gastrointestinal (GI) (diarrhoea/typhlitis/upper and lower GI haemorrhage). * Investigations (bilirubin). * Renal and Urinary (acute kidney injury/haematuria). * Nervous system (seizure).
The MTD of non-engraftment donor leukocyte infusions administered with fractionated gemtuzumab ozogamicin in patients with relapsed/refractory AML is determined by the dose level achieved with no Dose limiting toxicities. Measure = participants without DLTs. The recommended phase 2 dose (RP2D) or maximum tolerated dose (MTD) was evaluated by utilizing a 3+3 design to determine if 1-2x108 CD3 cells/kg can be safely administered with fractionated Gemtuzumab Ozogamicin administered on days 1,4 and 7 (total dose capped at 13.5 mg). The leukocyte infusion is administered on day 8 after completion of GO day 7. Two DLI dose levels well be assessed: DLI Dose Level 1: 1-2x107 CD3+ cells/kg DLI Dose Level 2: 1-2x108 CD3+ cells/kg The RP2D/MTD is determined by the dose level achieved with no Dose limiting toxicities. Measure = participants without DLTs through 35 days post DLI.
Response rate of infusional gemtuzumab ozogamicin followed by nonengraftment donor leukocyte infusions in patients with refractory acute myeloid leukemia. Bone Marrow Biopsy to be done in patients thought to have responded. Complete remission or complete remission with incomplete count recovery, after one cycle of treatment. Rationale for including CRi: CRi has previously been used in gemtuzumab ozogamicin trials because of incomplete platelet recovery seen with this drug.
| Arm | Type | Description |
|---|---|---|
| Mitoxantrone | ACTIVE_COMPARATOR | Course 1 * Mitoxantrone: 12 mg/m2 daily by IV infusion over 1 hour on days 1, 2, 3 and 4 (total 4 doses). * Cytarabine:100 mg/m2 12 hourly by IV bolus on days 1-10 inclusive (total 20 doses). Course 2 * Mitoxantrone: 12 mg/m2 daily by IV infusion over 1 hour on days 1, 2 and 3 (total 3 doses). * Cytarabine: 100 mg/m2 12 hourly by IV bolus on days 1-8 inclusive (total 16 doses). |
| Liposomal daunorubicin | EXPERIMENTAL | Randomisation 1 (R1)) closed early to recruitment on 8th September 2017, due to liposomal daunorubicin manufacturing issues resulting in unavailability of the drug. Course 1 * Liposomal daunorubicin: 80 mg/m2 daily by 1 hour IV infusion on days 1, 3 and 5 (total 3 doses). * Cytarabine: 100 mg/m2 12 hourly by IV bolus on days 1-10 inclusive (total 20 doses). Course 2 * Liposomal daunorubicin: 60 mg/m2 daily by 1 hour IV infusion on days 1, 3 and 5 (total 3 doses). * Cytarabine: 100 mg/m2 12 hourly by IV bolus on days 1-8 inclusive (total 16 doses). |
| Gemtuzumab Ozogamicin Dose Finding Study | EXPERIMENTAL | * Cohort 1: 1x3mg/m2 IV infusion over 2hours on day 4. * Cohort 2: 2x3mg/m2 IV infusion over 2hours on day 4 and day 7. * Cohort 3: 3x3mg/m2 IV infusion over 2hours on days 4, 7 and 10. |
| High dose cytarabine | ACTIVE_COMPARATOR | Two courses of Cytarabine: 3 g/m2 12 hourly by IV infusion over 4 hours on days 1, 3 and 5 (total 6 doses). |
| Fludarabine & cytarabine | EXPERIMENTAL | Two courses of: * Fludarabine: 30 mg/m2 daily by IV infusion over 30 minutes on days 1-5 inclusive (total 5 doses). * Cytarabine: 2 g/m2 daily by IV infusion over 4 hours on days 1-5 inclusive (total 5 doses).The cytarabine infusion should be started 4 hours after the start of the fludarabine infusion |
| Myeloablative conditioning | ACTIVE_COMPARATOR | * Busulfan Area Under the Curve (AUC) 70-100mg/L x hr by IV infusion over 3 hours, given 12 hourly on days -10 to -7 (8 doses). * Cyclophosphamide 50mg/kg/day by IV infusion over 1 hour, on days -5 to -2 (4 doses). |
| Reduced intensity conditioning | EXPERIMENTAL | * Busulfan AUC60-65mg/L X hr by IV infusion over 3 hours, given 12 hourly on days -5 to -2 (8 doses). * Fludarabine 30mg/m2/day by IV infusion over 30 minutes on days -8 to -3 (6 doses). |
| a | EXPERIMENTAL | 2 doses of gemtuzumab ozogamicn administered at monthly intervals |
| b | ACTIVE_COMPARATOR | 2 years maintenance therapy with intermittent ATRA plus 6-Mercaptopurine (6-MP) and methotrexate (MTX) |
| Phase 1 Treatment 1: Gemtuzumab Ozogamicin and DLI Dose Level 1 | EXPERIMENTAL | Day 8: The product will be administered unprocessed on day 8 (same day as leukapheresis) with a minimum of 1x10\^7 CD3+ cells and maximum of 2x10\^7 CD3+ cells/kg irrespective of the number of CD34+ cells. Patients who show a transient response to therapy can receive up to two additional donor leukocyte infusions with GO 6mg/m2 (2mg/m2 each day, capped at 4.5mg) for all patients regardless of age administered on days 1,4, and 7, no sooner than 35 days status post their last cellular infusion. |
| Phase 1 Treatment 2: Gemtuzumab Ozogamicin and DLI Dose Level 2 | EXPERIMENTAL | Day 8: The product will be administered unprocessed on day 8 (same day as leukapheresis) with a minimum of 1x10\^8 CD3+ cells and maximum of 2x10\^8 CD3+ cells/kg irrespective of the number of CD34+ cells. Patients who show a transient response to therapy can receive up to two additional donor leukocyte infusions with GO 6mg/m2 (2mg/m2 each day, capped at 4.5mg) for all patients regardless of age administered on days 1,4, and 7, no sooner than 35 days status post their last cellular infusion. |
| Phase 2 Treatment 3: Gemtuzumab Ozogamicin and DLI Dose Level (MTD determined from Phase1) | EXPERIMENTAL | Maximum Tolerated Dose (MTD) determined from Phase 1 portion of study Day 8: The product will be administered unprocessed on day 8 (same day as leukapheresis) with a dose of 1x10\^7 - 2x10\^7 CD3+ cells OR 1x10\^8 - 2x10\^8 CD3+ cells/kg irrespective of the number of CD34+ cells. MTD AS DETERMINED BY PHASE 1 Patients who show a transient response to therapy can receive up to two additional donor leukocyte infusions with GO 6mg/m2 (2mg/m2 each day, capped at 4.5mg) for all patients regardless of age administered on days 1,4, and 7, no sooner than 35 days status post their last cellular infusion. |
| Name | Type | Description |
|---|---|---|
| Gemtuzumab ozogamicin | DRUG | Antibody-conjugated chemotherapy agent. |
| Liposomal daunorubicin | DRUG | Anthracycline (Randomisation 1 (R1)) closed early to recruitment on 8th September 2017, due to liposomal daunorubicin manufacturing issues resulting in unavailability of the drug. |
| Mitoxantrone | DRUG | DNA-reactive agent |
| Fludarabine | DRUG | A water-soluble fluorinated nucleotide analogue of the antiviral agent vidarabine. |
| Cytarabine | DRUG | Pyrimidine nucleoside analogue, an antineoplastic agent. |
| Busulfan | DRUG | Alkylsulfonate |
| Cyclophosphamide | DRUG | A nitrogen mustard alkylating agent from the oxazaphosphorine group |
| ATRA plus 6-MP and MTX | DRUG | 6-MP 50 mg/m2/day PO; MTX 15 mg/m2/q week IM; ATRA 45 mg/m2/day PO |
| cytarabine. | DRUG | - |
| Mylotarg (gemtuzumab ozogamicin) Injection | DRUG | - |
| chemotherapy | DRUG | - |
| Gemtuzumab Ozogamicin (GO) | DRUG | Patients will be given gemtuzumab ozogamicin on days 1,4, and 7. Capped at 4.5mg individual doses. Total doses capped at 13.5mg. |
| Donor Leukocytes | OTHER | The product will be administered unprocessed on day 8/24 hours post GO (same day as leukapheresis) with a minimum of CD3+ cells and maximum of CD3+ cells/kg irrespective of the number of CD34+ cells. |
Inclusion Criteria: Inclusion criteria for trial entry * Diagnosis of acute myeloid leukaemia (AML) /high risk Myelodysplastic syndrome (MDS) (\>10% blasts in the bone marrow)/isolated myeloid sarcoma (MS) (either de novo or secondary). * Age \<18 years at trial entry. * No prior chemotherapy or b...
Mylotarg is used to treat acute myelogenous leukemia (AML), a cancer of the blood and bone marrow. It is an antibody-drug conjugate studied in patients with AML, including after stem cell transplant. Mylotarg is also known as Mylotarg (gemtuzumab ozogamicin) Injection.
Mylotarg is developed by Pfizer, Inc., which trades on the New York Stock Exchange under the ticker PFE. Pfizer is the company behind the gemtuzumab ozogamicin injection product.
Mylotarg has been studied in Phase 2 clinical development for acute myelogenous leukemia. The recorded Phase 2 trial has completed, and no trials for this asset are currently active.
Mylotarg was evaluated in the Phase 2 trial NCT00044733, titled Study Evaluating Gemtuzumab Ozogamicin in Acute Myelogenous Leukemia After Stem Cell Transplant. That trial enrolled 38 patients in the United States and has completed. It was an uncontrolled study without randomization or double blinding.
Yes. Mylotarg is the brand name for gemtuzumab ozogamicin, an antibody-drug conjugate given as an injection. People searching for gemtuzumab ozogamicin injection are looking at the same product as Mylotarg.
Yes. The Phase 2 trial of Mylotarg in acute myelogenous leukemia, NCT00044733, was biomarker selected, meaning patients were enrolled based on a biomarker. The study enrolled 38 patients of all sexes and included patients from birth onward, and it has completed.