A Phase II Study of Cladribine, Cytarabine, and Granulocyte-Colony Stimulating Factor With Fractionated Gemtuzumab Ozogamicin (CLAG-GO) for the Treatment of Patients With Persistent, Relapsed or Refractory Acute Myeloid Leukemia
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.
• At least 20% expression of CD33 as determined by flow cytometry or immunohistochemical staining.
• Adequate renal function, defined as a serum creatinine less than 1.8 mg/dL.
• Adequate hepatic function, defined as a direct bilirubin less than 2 times the institutional upper limit of normal (ULN) and AST, ALT and Alkaline Phosphatase less than 3 times the ULN.
• Patients who relapse after allogeneic hematopoietic stem cell transplantation are eligible, provided they are at least 60 days from stem cell infusion, do not have \> grade 1 graft versus host disease, and have been off all immunosuppressive therapy for at least 2 weeks.
• Female patients of childbearing potential must have a negative pregnancy test and agree to use an adequate method of contraception as defined by the protocol. This must persist through the treatment period until at least 6 months after the last dose of chemotherapy or GO.
⁃ Male subjects who are able to father children and are having intercourse with females of childbearing potential must also agree to an acceptable method of contraception through the treatment period until at least 3 months after the last dose of chemotherapy or GO, and must refrain from sperm donation during this period.
⁃ Ability to give written informed consent.