Treatment for patients with difficult-to-treat acute myeloid leukemia
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 is testing a new combination of chemotherapy drugs to see if it can help adults with tough-to-treat acute myeloid leukemia that hasn't responded to previous treatments.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 39 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | University of Maryland, Baltimore Academic / other |
| Drugs / interventions | gemtuzumab, chemotherapy |
| Locations | 1 site (Baltimore, Maryland) |
| Trial ID | NCT04050280 on ClinicalTrials.gov |
What this trial studies
This clinical trial evaluates the effectiveness of a chemotherapy combination known as CLAG-GO, which includes cladribine, cytarabine, granulocyte-colony stimulating factor, and gemtuzumab ozogamicin, in adult patients with acute myeloid leukemia (AML) that has either persisted or relapsed after initial treatment. The trial is a single-arm, two-stage phase II design conducted at the University of Maryland Greenebaum Comprehensive Cancer Center, aiming to enroll up to 39 patients. Participants will receive induction chemotherapy and will be monitored for response, with options for further treatment based on their outcomes. The study includes strict eligibility criteria to ensure the safety and appropriateness of the treatment for participants.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18 and older with a confirmed diagnosis of acute myeloid leukemia who have not responded to standard therapies.
Not a fit: Patients with acute promyelocytic leukemia or those who have not undergone prior intensive chemotherapy may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a new effective option for patients with relapsed or refractory acute myeloid leukemia.
How similar studies have performed: Other studies have shown promise with similar chemotherapy combinations, but this specific approach is being evaluated for the first time in this context.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
1. 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.
2. 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.
3. Eastern Cooperative Oncology Group performance status of 0-2.
4. 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.
5. At least 20% expression of CD33 as determined by flow cytometry or immunohistochemical staining.
6. Adequate renal function, defined as a serum creatinine less than 1.8 mg/dL.
7. 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.
8. 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.
9. 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.
10. 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.
11. Ability to give written informed consent.
Exclusion Criteria:
1. Patients with acute promyelocytic leukemia (FAB-M3) or chronic myelogenous leukemia in blast phase.
2. Isolated myeloid sarcoma. Patients must have marrow involvement with AML to enter the study.
3. Patients with known active AML involvement of the central nervous system.
4. Prior treatment with gemtuzumab ozogamicin or cladribine for AML. Prior treatment with cytarabine is permitted.
5. As patients will be receiving G-CSF prior to chemotherapy, patients presenting with symptomatic leukostasis (as judged by the investigator) are excluded. Hydroxyurea, 6-mercaptopurine and/or leukapheresis for blast count control (see inclusion criterion #4) for patients with asymptomatic hyperleukocytosis is permitted before starting treatment, but must be stopped for at least 24 hours prior to starting protocol treatment.
6. Active uncontrolled infection. Patients on prophylactic antibacterial, antifungal, and/or antiviral agents and patients whose infections are controlled with these agents are eligible.
7. Known active hepatitis B or C or other known active hepatic disorder.
8. Any history of veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS).
9. Active concurrent malignancy, unless disease-free for at least 3 years. Subjects with treated non-melanoma skin cancer, in situ carcinoma or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed. Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease are eligible if hormonal therapy has been initiated or the malignancy has been treated surgically or with definitive radiotherapy.
10. Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that per investigator's judgment would limit compliance with study requirements.
Where this trial is running
Baltimore, Maryland
- University of Maryland Greenebaumn Comprehensive Cancer Center — Baltimore, Maryland, United States (Recruiting)
Study contacts
- Principal investigator: Vu H. Duong, MD, MS — University of Maryland Greenebaumn Comprehensive Cancer Center
- Study coordinator: Veronica Kflu
- Email: veronica.kflu@umm.edu
- Phone: 410-328-9416
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.