Trial of DFP-10917 vs Non-Intensive or Intensive Reinduction for AML Patients in 2nd/3rd/4th Salvage

Phase 3 Randomized Trial of DFP-10917 vs Non-Intensive Reinduction (LoDAC, Azacitidine, Decitabine, Venetoclax Combination Regimens) or Intensive Reinduction (High & Intermediate Dose Cytarabine Regimens) for Acute Myelogenous Leukemia Patients in Second, Third, or Fourth Salvage

Phase III, multicenter, randomized study with two arms (1:1 ratio) enrolling patients with AML relapsed/refractory after 2, 3, or 4 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, Venetoclax Combination Regimens) or Intensive Reinduction (High and Intermediate Dose Cytarabine Regimens), depending on the patient's prior induction treatment.

Study Overview

• Status: Terminated
• Conditions: Leukemia, Myeloid, Acute
• Intervention / Treatment: Drug: Fludarabine; Drug: Mitoxantrone; Drug: Decitabine; Drug: Azacitidine; Drug: Venetoclax; Drug: DFP-10917; Drug: Cytarabine; Drug: Etoposide; Drug: Idarubicin; Drug: Cladribine

Detailed Description

Study to compare the rate of complete response (CR) and duration of CR, in patients with relapsed or refractory AML to two, three, or four 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, venetoclax + LoDAC or azacitidine or decitabine) or intensive reinduction (high and intermediate dose cytarabine regimens) as a second, third, or fourth 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, Venetoclax + LoDAC or Azacitidine or Decitabine) or Intensive Reinduction (High and Intermediate Dose Cytarabine Regimens), depending on the patient's prior induction treatment as well as the patient's clinical condition and comorbidities. 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.

Non-Intensive Reinduction:

• 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
• Venetoclax + LoDAC or Azacitidine or Decitabine: In combination with LoDAC, Venetoclax will be administered via a daily ramp-up to a final 600 mg once daily dose. During the ramp-up, patients are to receive TLS prophylaxis and may be hospitalized for monitoring. Cytarabine will be administered subcutaneously at a dose of 20 mg/m² once daily on Days 1-10 of each 28-day cycle beginning Cycle 1 Day 1. In combination with Azacitidine or Decitabine, Venetoclax will be administered via a daily ramp-up to a final 400 mg once daily dose. Azacitidine will be administered intravenously or subcutaneously at a dose of 75 mg/m² on Days 1-7 of each 28-day cycle beginning on Cycle 1 Day 1. Decitabine will be administered via IV at a dose of 20 mg/m² on Days 1-5 or 1-10, as per institutional practice, of each 28-day cycle beginning Cycle 1 Day 1.

Intensive Reinduction:

• 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 (Etoposide may be deleted per institutional guidelines, i.e., HAM regimen)
• CLAG/M or Ida = cladribine 5 mg/m² on Days 1-5, cytarabine 2 g/m² on Days 1-5, granulocyte-colony stimulating factor 300 μg on Days 0-5 (G-CSF starts 24 hr prior to chemotherapy), and mitoxantrone 10 mg/m² on Days 1-3 or Idarubicin 10 mg/m² on Days 1-3
• 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.

• Study Type: Interventional
• Enrollment (Actual): 167
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • O'Neal Comprehensive Cancer Center
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth (VGPCC Cancer Transplant Institute)
    • Tucson, Arizona, United States, 85724-5024
      • The University of Arizona Cancer Center
  • California
    • Irvine, California, United States, 92697
      • University of California
    • Los Angeles, California, United States, 90095
      • UCLA
  • Florida
    • Gainesville, Florida, United States, 32608
      • UF-Health Cancer Center Gainesville
    • Jacksonville, Florida, United States, 32207
      • Baptist MD Anderson
    • Jacksonville, Florida, United States, 32209
      • UF-Health Jacksonville
    • Orlando, Florida, United States, 32804
      • AdventHealth Medical Group Blood and Marrow Transplant at Orlando
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Cancer Center at Augusta University
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital-Cancer Care Specialists of Central IL
    • Hines, Illinois, United States, 60153
      • Loyola University Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Franciscan Health Indianapolis
  • Kansas
    • Westwood, Kansas, United States, 66205
      • The University of Kansas Cancer Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of KY- Markey Cancer Center
    • Louisville, Kentucky, United States, 40241
      • Norton Cancer Institute
  • Louisiana
    • Jefferson, Louisiana, United States, 70121
      • Ochsner Benson Cancer Center
    • New Orleans, Louisiana, United States, 70118
      • Tulane University
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Cancer Institute
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • The University of Mississippi Medical Center
  • New York
    • Valhalla, New York, United States, 10595
      • New York Medical College
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Cancer Institute - Elizabeth (Hematology)
    • Greenville, North Carolina, United States, 27834
      • East Carolina University
    • Kinston, North Carolina, United States, 28501
      • Vidant Oncology
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Comprehensive Cancer Center
    • Winston-Salem, North Carolina, United States, 27103
      • Novant Health Cancer Institute - Forsyth (Hematology)
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati Cancer Center
    • Cleveland, Ohio, United States, 44106
      • Seidman Cancer Center, University Hospitals, Cleveland Medical Center
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Cancer Institute
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Medical Group
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Health System
  • Washington
    • Spokane, Washington, United States, 99218
      • MultiCare Institute for Research and Innovation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically or pathologically confirmed diagnosis of AML based on WHO classification that has relapsed after, or is refractory to, two, three, or four 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 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.)

   Patients with a history of IPSS-R high or very high risk MDS that transformed to AML during treatment with hypomethylating drugs and then relapse following or are refractory to a subsequent AML induction regimen may be enrolled as Second Salvage AML patients. Additionally, patients with a history of MPN in accelerated phase (MPN-AP) or high-risk primary myelofibrosis (PMF) that transformed to AML during treatment with hypomethylating drugs and then relapse following or are refractory to a subsequent AML induction regimen may be enrolled as Second Salvage AML patients.

2. Aged ≥ 18 years.
3. 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.

Exclusion Criteria:

1. 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 the initiation of study treatment. At the investigator's discretion, for patients with significant leukocytosis that develops during the early treatment cycles, hydroxyurea may be administered. The hydroxyurea should be discontinued as soon as clinically appropriate.
2. Any >grade 1 persistent clinically significant toxicities from prior chemotherapy.
3. Inadequate Cardiac (left ventricular ejection fraction ≤40%) function.
4. White blood cell (WBC) count >15,000/μL (Note: Patients considered for possible venetoclax-containing regimen must have WBC ≤10k/μL prior to initiating venetoclax treatment).

5. For patients with prior hematopoietic stem cell transplant (HSCT):

   1. Less than 3 months since HSCT
   2. Acute Graft versus Host Disease (GvHD) >Grade 1
   3. Chronic GvHD >Grade 1
6. Any concomitant condition that in the opinion of the investigator could compromise the objectives of this study and the patient's compliance.
7. A pregnant or lactating woman.
8. 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.
9. Patient has acute promyelocytic leukemia (APL).
10. Patients with known HIV, active HBV or active HCV infection (note: testing for these infections is not required). For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
11. Documented or known clinically significant bleeding disorder.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; 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	Drug: DFP-10917; DFP-10917 Powder for Injection. Active ingredient: 4-amino-1-(2-cyano-deoxy-β-D-arabinofuranosyl)-2(1H)-pyrimidinone monohydrochloride
Active Comparator: Control; Non-Intensive: LoDAC: 20 mg SC BID 10 days; Azacitidine: 75 mg/m²/day SC 7 days(or 5+2); Decitabine: CIV 20 mg/m²x5 days; Venetoclax + LoDAC/Azacitidine/Decitabine:LoDAC-Venetoclax ramp-up to 600 mgxday. Cytarabine SC 20 mg/m²xday D1-10. Azacitidine or Decitabine-Venetoclax ramp-up to 400 mgxday. Azacitidine IV or SC 75 mg/m² D1-7. Decitabine IV 20 mg/m² on D1-5 or 1-10. Intensive: High DAC: cytarabine 1-2 g/m² up to 5 days, max total dose 10 g/m²; FLAG: D1-5: fludarabine 30 mg/m² IV for 30min, D1-5: cytarabine 1-2 g/m² for 4hr daily x 5 & G-CSF 5 mcg/kg or 300 mcg/m² until PMN recovery, with or without idarubicin D1-3 8 mg/m² IV dailyx3 (FLAG-Ida); MEC: D1-6: mitoxantrone 6 mg/m² IV bolus, etoposide 80 mg/m² IV 1hr & cytarabine 1g/m² IV 6hr.; CLAG/M or Ida = cladribine 5 mg/m² D1-5, cytarabine 2 g/m² D1-5, G-CSF 300 μg D0-5, mitoxantrone 10 mg/m² D1-3 or Idarubicin 10 mg/m² D1-3.; Intermediate DAC: cytarabine 20 mg/m² IV dailyx5	Drug: Fludarabine; Fludarabine; Drug: Mitoxantrone; Mitoxantrone; Drug: Decitabine; Decitabine; Drug: Azacitidine; Azacitidine; Drug: Venetoclax; Venetoclax; Drug: Cytarabine; cytosine arabinoside (ara-C); Drug: Etoposide; Etoposide; Drug: Idarubicin; Idarubicin; Drug: Cladribine; Cladribine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remission (CR) rate	The rate of CR based on International Working Group (IWG) Guidelines for bone marrow and blood response	3 years
Duration of complete remission	Number of days from time of initial CR until disease recurrence or death	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of complete remission (CR) + (complete remission with incomplete hematologic recovery) CRi+ (complete remission with partial hematologic recovery) CRp	CR as above including neutrophil granulocyte count > 0.5x10^9/L & platelet count > 50x10^9/L	3 years
The duration of complete remission (CR) + (complete remission with incomplete hematologic recovery) CRi+ (complete remission with partial hematologic recovery) CRp	CR as above including neutrophil granulocyte count > 0.5x10^9/L & platelet count > 50x10^9/L + platelet count < 100x10^9/L	3 years
Overall survival	Number of days from date of first dose to date of death	3 years
Transition rate to hematopoietic stem cell transplantation (HSCT)	Number of subjects who transition to HSCT	3 years
Overall response rate (ORR)	The rate of CR + CRi + CRp + PR	3 years
Duration overall response	The duration of CR + CRi + CRp + PR	3 years
Rate of disease related co-morbidities	Number and severity of expected leukemia-related adverse events	3 years
Adverse events	Number of patients with adverse events	3 years

Collaborators and Investigators

• Sponsor: Delta-Fly Pharma, Inc.
• Investigators: Principal Investigator: Tapan Kadia, MD, M.D. Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2019
• Primary Completion (Actual): January 7, 2026
• Study Completion (Actual): January 7, 2026

Study Registration Dates

• First Submitted: April 11, 2019
• First Submitted That Met QC Criteria: April 23, 2019
• First Posted (Actual): April 24, 2019

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 21, 2026
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleic Acids, Nucleotides, and Nucleosides; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glucosides; Glycosides; Purines; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Arabinonucleosides; Anthracyclines; Naphthacenes; Aminoglycosides; Daunorubicin; Anthraquinones; Anthrones; Anthracenes; Quinones; Deoxyribonucleosides; 2-Chloroadenosine; Adenosine; Purine Nucleosides; Deoxyadenosines; Decitabine; Cytarabine; Etoposide; Azacitidine; Mitoxantrone; Cladribine; Idarubicin; fludarabine; venetoclax; DFP-10917
• Other Study ID Numbers: D18-11141

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No