This study involves evaluating a combination of chemotherapy drugs known as "CLAG-GO" \[cladribine, cytarabine, granulocyte-colony stimulating factor (G-CSF) and gemtuzumab ozogamicin (GO)\] in the treatment of acute myeloid leukemia (AML) that has not responded well to standard therapy or has returned after an initial remission (relapsed). The trial will be conducted at the University of Maryland Greenebaum Comprehensive Cancer Center (UMGCCC). Potential participants will go through a screening period to see if they are eligible to join the study. If eligible, participants will be hospitalized for 4-5 weeks to receive study treatment with CLAG-GO, called induction chemotherapy. If tests show that the cancer is in remission after induction chemotherapy, participants may undergo further chemotherapy (known as consolidation) or may proceed with bone marrow/stem cell transplantation. Patients who receive consolidation chemotherapy and remain in remission may have up to 8 cycles of outpatient maintenance therapy. A cycle lasts about 28 days. All participants will be monitored carefully for both side effects and to see if the study treatment is working. Lab tests and exams will be conducted throughout the entire study. In addition, special studies will be done at various time points to try to understand better how the drugs work and which patients are likely to respond best.
Adult patients age 18 years or older, with a pathologically confirmed diagnosis of AML [excluding acute promyelocytic leukemia (APL)] according to WHO criteria. AML may be de novo, or following a prior hematologic disease and/or therapy-related.
Patients must have relapsed after or be refractory to at least one course of an intensive chemotherapy regimen, for example anthracycline/cytarabine ("7+3" or daunorubicin and cytarabine liposome). Patients with residual disease on day 13-22 of initial induction chemotherapy are eligible, provided the bone marrow cellularity is ≥ 30% AND bone marrow blasts are ≥ 20%. Hypomethylating agents such as azacitidine or decitabine are allowed as a prior therapy, but are not considered an intensive chemotherapy regimen.
Eastern Cooperative Oncology Group performance status of 0-2.
Any systemic chemotherapy and any radiotherapy must be completed at least 7 days prior to initiation of protocol therapy, with the exception of hydroxyurea or 6-mercaptopurine for cytoreduction.
Patients with acute promyelocytic leukemia (FAB-M3) or chronic myelogenous leukemia in blast phase.
Isolated myeloid sarcoma. Patients must have marrow involvement with AML to enter the study.
Patients with known active AML involvement of the central nervous system.
Prior treatment with gemtuzumab ozogamicin or cladribine for AML. Prior treatment with cytarabine is permitted.
Single group
Cladribine, Cytarabine, and Granulocyte-Colony Stimulating Factor with Fractionated Gemtuzumab Ozogamicin (CLAG-GO)
DrugInduction: G-CSF 300 mcg subcutaneously daily on days 0-5. Cladribine 5 mg/m2 in normal saline given intravenously over 2 hours daily on days 1-5. Cytarabine 2000 mg/m2 in normal saline given intravenously over 4 hours daily on days 1-5. Gemtuzumab ozogamicin 3 mg/m2 intravenously over 2 hours on days 1 and 4, prior to cladribine and cytarabine. Consolidation: If CRMRD-, CR or CRi is confirmed by bone marrow biopsy and aspirate after induction chemotherapy, patients may receive one cycle of consolidation chemotherapy (at the discretion of the investigator) with the same CLAG-GO regimen at the same doses given for induction. In addition, the investigator has the option of giving CLAG alone without GO if there is concern for increased risk of sinusoidal obstruction syndrome. Patients who remain in CRMRD-, CR or CRi after consolidation chemotherapy may receive up to eight infusions of GO 2 mg/m2 approximately every 28 days.
Response Rate (Efficacy)
Responses will be judged according to modified European LeukemiaNet recommendations published in 2017. Patients who achieve either 1) complete remission without minimal residual disease, 2) complete remission, or 3) complete remission with incomplete hematologic recovery will be considered responders
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
All adverse events will be graded according to CTCAE version 5.
Presence of minimal residual disease
This is determined by flow cytometry completed through Hematologics, Inc.
Time to relapse or death
Time to relapse is measured from the date of confirmed remission until the date of confirmed relapse. Time to death (survival) is measured from the date of enrollment until the date of death, assessed up to 2 years.
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University of Maryland, Baltimore
Lead sponsor
Hematologics, Inc
Collaborator
