Trial of DFP-10917 vs Non-Intensive or Intensive Reinduction for AML Patients in 2nd/3rd Salvage
Phase III, multicenter, randomized study with two arms (1:1 ratio) enrolling patients with AML relapsed/refractory after 2 or 3 prior induction regimens: Experimental arm: DFP-10917 14-day continuous intravenous (IV) infusion at a dose of 6 mg/m²/day followed by a 14-day resting period per 28-day cycles. Control arm: Non-Intensive Reinduction (LoDAC, Azacitidine, Decitabine) or Intensive Reinduction (High and Intermediate Dose Cytarabine Regimens), depending on the patient's prior induction treatment.
- Leukemia, Myeloid, Acute
- Eligible Ages
- Over 18 Years
- Eligible Genders
- Accepts Healthy Volunteers
- Histologically or pathologically confirmed diagnosis of AML based on World Health Organization (WHO) classification that has relapsed after, or is refractory to, two or three prior induction regimens that may have included intensive chemotherapy (e.g., "7+3" cytarabine and daunorubicin), epigenetic therapy (i.e., azacitidine or decitabine) , or targeted therapy (e.g., FLT-3, IDH-1/2, BCL-2, monoclonal antibody).
(Relapse is defined as reemergence of ≥5% leukemia blasts in bone marrow or ≥1% blasts in peripheral blood 90 days to 24 months after first CR or CR without complete platelet recovery (CRp). Refractory AML is defined as persistent disease ≥28 days after initiation of intensive induction therapy (up to two induction cycles) or relapse <90 days after first CR or CRp. Refractory disease for patients undergoing hypomethylating agent induction is defined as lack of remission following at least 2 cycles of epigenetic therapy without reduction in bone marrow blast status.)
2. Aged ≥ 18 years.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.
4. Adequate clinical laboratory values (i.e., plasma creatinine < 2.5 x upper limit of normal (ULN) for the institution, bilirubin < 2.5 x ULN, alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5 x ULN).
5. Absence of active central nervous system (CNS) involvement by leukemia. Patients with previously diagnosed CNS leukemia are eligible if the CNS leukemia is under control and intrathecal treatment may continue throughout the study.
6. Absence of uncontrolled intercurrent illnesses, including uncontrolled infections, cardiac conditions, or other organ dysfunctions.
7. Signed informed consent prior to the start of any study specific procedures.
8. Women of child-bearing potential must have a negative serum or urine pregnancy test.
9. Male and female patients must agree to use acceptable contraceptive methods for the duration of the study and for at least one month after the last drug administration.
- The interval from prior treatment to time of study drug administration is < 2 weeks for cytotoxic agents or < 5 half-lives for noncytotoxic agents. Exceptions: Use of hydroxyurea is allowed before the start of study and is to be discontinued prior to randomization. Hydroxyurea may be administered before study start and up to the time of study randomization. At the investigator's discretion, for patients with significant leukocytosis during the early treatment cycles, hydroxyurea may be administered. The hydroxyurea should be discontinued as soon as clinically appropriate.
- Any >grade 1 persistent clinically significant toxicities from prior chemotherapy.
- Cardiac (left ventricular ejection fraction ≤40%) function.
- White blood cell (WBC) >15,000/uL.
- For patients with prior hematopoietic stem cell transplant (HSCT):
- Less than 3 months since HSCT
- Acute Graft versus Host Disease (GvHD) >Grade 1
- Chronic GvHD >Grade 1
- Any concomitant condition that in the opinion of the investigator could compromise the objectives of this study and the patient's compliance.
- A pregnant or lactating woman.
- Current malignancies of another type. Exceptions: Patients may participate if they have previously treated and currently controlled prostate cancer, or adequately treated in situ cervical cancer or basal cell skin cancer, or other malignancies with no evidence of disease for 2 years or more.
- Patient has acute promyelocytic leukemia (APL).
- Patients with known HIV, HBV or HCV infection (note: testing for these infections is not required).
- Documented or known clinically significant bleeding disorder.
- Phase 3
- Study Type
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- randomized, controlled
- Primary Purpose
- None (Open Label)
|DFP-10917 Dose: 6 mg/m²/day administered by continuous infusion for 14 days followed by a 14-day resting period per 28-day treatment cycle. If a patient experiences a significant treatment-related AE, the patient may undergo one dose reduction of DFP-10917 to 4 mg/m²/day x 14 days for subsequent treatment cycles||
|Non-Intensive or Intensive Reinduction Non-Intensive: LoDAC: 20 mg Cytarabine SC injection BID 10days + best supportive care per 28day cycle Azacitidine: 75 mg/m²/day SC 7 days (or 5+2) + best supportive care per 28day cycle Decitabine: CIV 20 mg/m² x 5 days + best supportive care per 28day cycle Intensive: High DAC: cytarabine doses 1-2 g/m²/day up to 5days, max total dose 10 g/m² per course FLAG: Days 1-5: fludarabine 30 mg/m² IV for 30min, Days 1-5: cytarabine 1-2 grm/m² for 4hr daily x 5 & G-CSF 5 mcg/kg or 300 mcg/m² until PMN recovery, with or without idarubicin Days 1-3 at 8 mg/m² IV daily x 3 (FLAG-Ida) MEC: Days 1-6: mitoxantrone 6 mg/m² IV bolus, etoposide 80 mg/m² IV 1hr & cytarabine 1 grm/m² IV 6hr Intermediate DAC: cytarabine 20 mg/m² IV daily x 5||
- Delta-Fly Pharma, Inc.
Study ContactKiran Naqvi
Study to compare the rate of complete response (CR) and duration of CR, in patients with relapsed or refractory AML to two or three prior induction regimens that may have included intensive chemotherapy (e.g., "7+3" cytarabine and daunorubicin), epigenetic therapy (i.e., azacitidine or decitabine), or targeted therapy (e.g., FLT-3, IDH-1/2, BCL-2, monoclonal antibody), who will receive DFP-10917 versus non-intensive reinduction (LoDAC, azacitidine, decitabine) or intensive reinduction (high and intermediate dose cytarabine regimens) as a second or third salvage treatment.
Experimental Arm DFP-10917 Dose: 6 mg/m²/day administered by continuous infusion for 14 days followed by a 14-day resting period per 28-day treatment cycle. If a patient experiences a significant treatment-related AE, the patient may undergo one dose reduction of DFP-10917 to 4 mg/m²/day x 14 days for subsequent treatment cycles
Control arm: Non-Intensive Reinduction (LoDAC, Azacitidine, Decitabine) or Intensive Reinduction (High and Intermediate Dose Cytarabine Regimens), depending on the patient's prior induction treatment. Control treatment is to be selected only from among the following. Institutional practice for administering these treatments are permitted, but the dose and days of drug administration should be followed as below.
- LoDAC: 20 mg Cytarabine administered by subcutaneous (SC) injection, twice daily (BID) for 10 days, plus best supportive care per 28-day treatment cycle
- Azacitidine: 75 mg/m²/day administered by SC for 7 consecutive days (or 5+2), plus best supportive care per 28-day treatment cycle
- Decitabine: administered as continuous intravenous (CIV) infusion 20 mg/m² x 5 days plus best supportive care per 28 day treatment cycle
- High DAC = cytarabine at doses of 1-2 g/m²/day for up to 5 days, with a maximum total dose 10 g/m² per course
- FLAG = Days 1-5: fludarabine 30 mg/m² IV over 30 minutes, Days 1-5: cytarabine 1 2 grm/m² over 4 hours daily x 5, and granulocyte colony-stimulating factor 5 mcg/kg or 300 mcg/m² until Polymorphonuclear Neutrophil (PMN) recovery, with or without idarubicin Days 1-3 at 8 mg/m² IV daily x 3 (FLAG-Ida)
- MEC = Days 1-6: mitoxantrone 6 mg/m² IV bolus, etoposide 80 mg/m² IV over 1 hour, and cytarabine 1 grm/m² IV over 6 hrs
- Intermediate DAC = cytarabine 20 mg/m² IV daily x 5
The selection of control arm treatment will be determined by the investigator depending on the patient's prior initial induction and salvage treatment regimen(s), as well as the patient's clinical condition and comorbidities. The investigator will select the patient's control treatment from among the non-intensive or intensive regimens prior to study treatment randomization in order to balance treatment allocation between the experimental and control treatment arms.