Acute Myeloid Leukemia (AML) in Remission
Conditions
Keywords
Acute Myeloid Leukemia, Remission
Brief summary
This is a phase IB/II study with a 3+3 dose de-escalation study design. Patients will continue maintenance treatment with CPX-351 for 6 cycles on D1 and D3, as long as patient remains in CR. The dose de-escalation will be one dose given on D1 only, every 28 days pending toxicity. The maximum tolerated dose will be used for the phase II expansion portion of the study.
Interventions
DRUGCPX-351
Daunorubicin 8.8mg/m2 + cytarabine 20mg/m2
Sponsors
Georgetown University
Jazz Pharmaceuticals
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose de-escalation of CPX-351
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Newly diagnosed patients \> 18 years of age * Patients must be in CR or CRh (complete remission with partial count recovery). * Must have received ANY induction treatment with standard consolidation or hypomethylating agent (HMA) + venetoclax, for up to 6 cycles or no more than 12 cycles of treatment. * Must be able to start therapy within 3 months of last documented CR * De novo or secondary AML/treatment related AML (non-M3) including AML with myelodysplasia-related changes (MRC), histologically confirmed * Patients must be ineligible for allogeneic BMT (for any reason including poor performance status, patient's preference, favorable AML not a candidate for transplant, or comorbidities and age precluding from transplant etc) * Cardiac ejection fraction ≥ 50% by transthoracic echocardiography or MUGA scan * Adequate hepatic and renal function defined as: * Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 3 x upper limit of normal (ULN) * Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 3 is permissible if due to disease. * Bilirubin ≤3 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin) * Estimated Creatinine Clearance ≥30 ml/min (Cockcroft-Gault based on actual weight) (See Appendix A) * Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 3 (Appendix A) * Female subjects who are of non-reproductive potential (i.e., post-menopausal by history - no menses for ≥1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy). Female subjects of childbearing potential must have a negative serum pregnancy test upon study entry. * Male and female subjects who agree to use highly effective methods of birth control (e.g., condoms, implants, injectables, combined oral contraceptives, some intrauterine devices \[IUDs\], sexual abstinence, or sterilized partner) during the period of therapy and for at least 6 months after the last dose of study drug
Exclusion criteria
* Prior allogeneic transplant * Previous cumulative anthracycline (doxorubicin equivalent) dose equal to or greater than 345 mg/m2, and for patients with prior mediastinal XRT, anthracycline dose equal to or greater than 295 mg/m2 * Acute promyelocytic leukemia \[t(15;17)\] * If patient is unable to sign informed consent due to any serious medical condition, laboratory abnormality or psychiatric illness * Patients with evidence of uncontrolled current myocardial impairment (e.g. unstable ischemic heart disease, uncontrolled arrhythmia, symptomatic valvular dysfunction not controlled on medical therapy, uncontrolled hypertensive heart disease, and uncontrolled congestive heart failure) * History of Wilson's disease or other copper-related disorders * History of allergic reactions attributed to compounds of similar composition to cytarabine and daunorubicin or liposomal products * History of other malignancies, except: * Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician. * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. * Adequately treated low risk prostate cancer or carcinoma in situ without evidence of disease. * Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE, version 4.03), grade ≤1, or to the levels dictated in the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerate dose (Phase 1) | 1 cycle (28 day cycle) | Number of subjects with Dose Limiting toxicities will be used to determine the recommended phase II dose of CPX-351 to be used in the maintenance setting for newly diagnosed AML in complete remission. |
| Inicidence of Treatment Emergent Adverse events (Phase 2) | 6 cycles (28 day cycles) | To determine the safety, tolerability and toxicity of CPX-351 in the maintenance setting for newly diagnosed AML in complete remission by analyzing the incidence of treatment emergent adverse events reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment Emergent Adverse Events (Phase 1) | 6 cycles (28 day Cycle) | To determine the safety, tolerability and toxicity of CPX-351 in the maintenance setting for newly diagnosed AML in complete remission by analyzing the incidence of treatment emergent adverse events reported. |
| Overall Survival (Phase 1 and 2) | 1 year after end of treatment | Determine the efficacy of CPX-351 as maintenance treatment in newly diagnosed AML patients who have achieved remission after induction treatment as measured by overall survival of subjects. |
| Event free survival (Phase 1 and 2) | 1 year after end of treatment | Determine efficacy of CPX-351 as maintenance treatment in newly diagnosed AML patients who have achieved remission after induction treatment as measured by event free survival. |
| Relapse Free Survival (Phase 1 and 2) | 1 year after end of treatment | Determine efficacy of CPX-351 as maintenance treatment in newly diagnosed AML patients who have achieved remission after induction treatment as measured by relapse free survival. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORKimberley Doucette, MD
Georgetown University
Outcome results
None listed