Cladribine in Combination With CAG in Patients With Refractory/Relapsed Acute Myeloid Leukemia

Efficacy and Safety of Cladribine in Combination With G-CSF, Low-dose Cytarabine and Aclarubicin in Patients With Refractory/Relapsed Acute Myeloid Leukemia: a Phase 2 Clinical Trial

The vast majority of patients with AML will die of the disease, and no standard chemotherapy regimen were defined for patients with relapsed/refractory AML. Previous studies have confirmed the efficacy of cladribine in the treatment of AML, both de novo or relapse/refractory AML. Our previous experience has shown that Cladribine in combination of CAG (G-CSF priming, low dose cytarabine, and aclarubicin) are effective with tolerable toxicity profiling.Thus, this phase 2 clincial trial is going to evaluate the efficacy and safety of cladribine in combination with G-CSF, low-dose cytarabine and aclarubicin (C-CAG) in patients with refractory/relapsed acute myeloid leukemia.

Study Overview

• Status: Unknown
• Conditions: Acute Myeloid Leukemia; Relapse Leukemia
• Intervention / Treatment: Drug: Cladribine; Drug: G-CSF; Drug: Aclarubicin; Drug: Cytarabine

Detailed Description

AML is most common in the elderly patients, who can not tolerate the intensified treatments. The vast majority of patients with AML will die of the disease, and no standard chemotherapy regimen were defined for patients with relapsed/refractory AML. Previous studies have confirmed the efficacy of cladribine in the treatment of AML, both de novo or relapse/refractory AML. Our previous experience has shown that Cladribine in combination of CAG (G-CSF priming, low dose cytarabine, and aclarubicin) are effective with tolerable toxicity profiling.Thus, this phase 2 clincial trial is going to evaluate the efficacy and safety of cladribine in combination with G-CSF, low-dose cytarabine and aclarubicin (C-CAG) in patients with refractory/relapsed acute myeloid leukemia.

• Study Type: Interventional
• Enrollment (Anticipated): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Liang Wang
      • Contact: Liang Wang, M.D.; Phone Number: +862087342439; Email: wangliang@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 73 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women;
• Clinical diagnosis of Relapsed/Refractory AML (non-APL);
• ECOG performance status (PS) score 0-3;
• AST and ALT <=2.5 times the institutional ULN;
• Total bilirubin <=2.0 times the institutional ULN
• Serum creatinine<2.0 times the institutional ULN;
• Subjects should take effective contraceptive measures，and serum or urine pregnancy tests must be negative during the screening and study periods in women subjects;
• Patients should understand the disease and voluntarily receive the study regimen and follow-up.

Exclusion Criteria:

• Concurrent diagnosis of tumors other than AML, with exclusion of superficial bladder cancer, basal cell and squamous cell carcinoma, cervical intraepithelial neoplasms (CIN), prostatic intraepithelial neoplasms(PIN);
• Active viral or bacterial infection that would impair the ability of the subject to receive protocol therapy;
• Concurrent autoimmune hemolytic anemia or immune thrombocytopenia;
• Subjects suffered from AIDS，active hepatitis B or C virus infection; 垫·Dementia or altered mental status that would prohibit the understanding or rendering of informed consent;
• Be allergic to any component of C-CAG regimen;
• Subjects ever exposed to cladribine or CAG-based regimen.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: treatment arm; The patients in this arm will receive C-CAG regimen for salvage treatment,detailed as following: Cladribine 5mg/㎡，d1-5；G-CSF 300ug,d0-9; aclarubicin 10mg,d3-6;cytarabine 10mg/㎡ q12h, SC, d3-9;4 weeks a cycle	Drug: Cladribine; 5mg/㎡ d1-5; Other Names: cladribine injection; Drug: G-CSF; 300ug d0-9; Other Names: granulocyte; Drug: Aclarubicin; 10mg d3-6; Other Names: Aclacinomycin; Drug: Cytarabine; 10mg/㎡ q12h SC d3-9; Other Names: Ara-C

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Remission (CR) rate	Less than 5% of blast cells in bone marrow aspiration is defined as CR.	Bone marrow aspiration will be done within 2 weeks after blood cell count recovery (about 4 weeks after initiation of C-CAG treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	The hematologic toxicities and non-hematologic toxicities will be graded according to CTCAE version 3.0	From initiation of C-CAG treatment to end of the study (about within 3 months since enrollment)

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Liang Wang, M.D., Sun Yat-Sen Univerisity

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Anticipated): December 31, 2019
• Study Completion (Anticipated): December 31, 2019

Study Registration Dates

• First Submitted: June 7, 2017
• First Submitted That Met QC Criteria: June 7, 2017
• First Posted (Actual): June 9, 2017

Study Record Updates

• Last Update Posted (Actual): August 20, 2019
• Last Update Submitted That Met QC Criteria: August 18, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: ACUTE MYELOID LEUKEMIA; CLADRIBINE
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Adjuvants, Immunologic; Antibiotics, Antineoplastic; Cytarabine; Cladribine; Aclarubicin; Aclacinomycins
• Other Study ID Numbers: C-CAG in AML

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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