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

NCT03926624 | Terminated Phase 3 DMC FDA Drug

• 1 other identifier: D18-11141
• Study Type: interventional
• Target: 167
• Locations: 1 country
• Sites: 39

Brief Summary

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.

Conditions

Leukemia, Myeloid, Acute

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (8)

• The rate of complete remission (CR) + (complete remission with incomplete hematologic recovery) CRi+ (complete remission with partial hematologic recovery) CRp

  3 years

• The duration of complete remission (CR) + (complete remission with incomplete hematologic recovery) CRi+ (complete remission with partial hematologic recovery) CRp

  3 years

• Overall survival

  3 years

• Transition rate to hematopoietic stem cell transplantation (HSCT)

  3 years

• Overall response rate (ORR)

  3 years

Study Arms (2)

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

Control

ACTIVE COMPARATOR

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: Cytarabine; Drug: Azacitidine; Drug: Decitabine; Drug: Mitoxantrone; Drug: Etoposide; Drug: Fludarabine; Drug: Idarubicin; Drug: Venetoclax; Drug: Cladribine

Interventions

DFP-10917 DRUG

DFP-10917 Powder for Injection. Active ingredient: 4-amino-1-(2-cyano-deoxy-β-D-arabinofuranosyl)-2(1H)-pyrimidinone monohydrochloride

Experimental

Cytarabine DRUG

cytosine arabinoside (ara-C)

Control

Decitabine DRUG

Decitabine

Control

Mitoxantrone DRUG

Mitoxantrone

Control

Etoposide DRUG

Etoposide

Control

Fludarabine DRUG

Fludarabine

Control

Idarubicin DRUG

Idarubicin

Control

Venetoclax DRUG

Venetoclax

Control

Cladribine DRUG

Cladribine

Control

Azacitidine DRUG

Azacitidine

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Aged ≥ 18 years.
• ECOG Performance Status of 0, 1 or 2.
• 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).
• 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.
• Absence of uncontrolled intercurrent illnesses, including uncontrolled infections, cardiac conditions, or other organ dysfunctions.
• Signed informed consent prior to the start of any study specific procedures.
• Women of child-bearing potential must have a negative serum or urine pregnancy test.
• 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.

You may not qualify if:

• 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.
• Any \>grade 1 persistent clinically significant toxicities from prior chemotherapy.
• Inadequate Cardiac (left ventricular ejection fraction ≤40%) function.
• 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).
• 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, 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.
• Documented or known clinically significant bleeding disorder.

Sponsors & Collaborators

• Delta-Fly Pharma, Inc.: lead

Study Sites (39)

O'Neal Comprehensive Cancer Center

Birmingham, Alabama, 35294, United States

Location

Banner MD Anderson

Gilbert, Arizona, 85234, United States

Location

HonorHealth (VGPCC Cancer Transplant Institute)

Scottsdale, Arizona, 85258, United States

Location

The University of Arizona Cancer Center

Tucson, Arizona, 85724-5024, United States

Location

University of California

Irvine, California, 92697, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

UF-Health Cancer Center Gainesville

Gainesville, Florida, 32608, United States

Location

Baptist MD Anderson

Jacksonville, Florida, 32207, United States

Location

UF-Health Jacksonville

Jacksonville, Florida, 32209, United States

Location

AdventHealth Medical Group Blood and Marrow Transplant at Orlando

Orlando, Florida, 32804, United States

Location

Georgia Cancer Center at Augusta University

Augusta, Georgia, 30912, United States

Location

Rush University

Chicago, Illinois, 60612, United States

Location

Decatur Memorial Hospital-Cancer Care Specialists of Central IL

Decatur, Illinois, 62526, United States

Location

Loyola University Medical Center

Hines, Illinois, 60153, United States

Location

Franciscan Health Indianapolis

Indianapolis, Indiana, 46237, United States

Location

The University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

University of KY- Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40241, United States

Location

Ochsner Benson Cancer Center

Jefferson, Louisiana, 70121, United States

Location

Tulane University

New Orleans, Louisiana, 70118, United States

Location

Henry Ford Cancer Institute

Detroit, Michigan, 48202, United States

Location

The University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

Novant Health Cancer Institute - Elizabeth (Hematology)

Charlotte, North Carolina, 28204, United States

Location

East Carolina University

Greenville, North Carolina, 27834, United States

Location

Vidant Oncology

Kinston, North Carolina, 28501, United States

Location

Novant Health Cancer Institute - Forsyth (Hematology)

Winston-Salem, North Carolina, 27103, United States

Location

Wake Forest Baptist Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

University of Cincinnati Cancer Center

Cincinnati, Ohio, 45267, United States

Location

Seidman Cancer Center, University Hospitals, Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Prisma Health Cancer Institute

Greenville, South Carolina, 29605, United States

Location

Avera Medical Group

Sioux Falls, South Dakota, 57105, United States

Location

UT Southwestern

Dallas, Texas, 75390, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22903, United States

Location

Multicare Institute for Research and Innovation

Spokane, Washington, 99218, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

DFP-10917; Cytarabine; Azacitidine; Decitabine; Mitoxantrone; Etoposide; fludarabine; Idarubicin; venetoclax; Cladribine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Aza Compounds; Organic Chemicals; Ribonucleosides; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Quinones; Polycyclic Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Glycosides; Carbohydrates; Daunorubicin; Anthracyclines; Naphthacenes; Aminoglycosides; 2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyadenosines; Deoxyribonucleosides

Study Officials

• Tapan Kadia, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: randomized, controlled

Study Record Dates

• First Submitted: April 11, 2019
• First Posted: April 24, 2019
• Study Start: November 22, 2019
• Primary Completion: January 7, 2026
• Study Completion: January 7, 2026
• Last Updated: January 22, 2026

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (39)