Clofarabine, Idarubicin, and Cytarabine (CIA) Versus Fludarabine, Idarubicin, and Cytarabine (FLAI) in Acute Myelogenous Leukemia (AML) and High-Risk Myelodysplastic Syndrome

NCT01289457 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 2010-0788NCI-2011-00251
• Study Type: interventional
• Target: 282
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if the combination of clofarabine, idarubicin, and cytarabine, or the combination of fludarabine, idarubicin, and cytarabine can help control Acute myeloid leukemia (AML) and Myelodysplastic syndromes (MDS). The safety of these study drug combinations will also be studied.

Conditions

Leukemia

Keywords

Acute Myelogenous Leukemia; AML; High-Risk Myelodysplastic Syndrome; MDS; Relapsed; Refractory; Clofarabine; Clofarex; Clolar; Idarubicin; Idamycin; Cytarabine; Ara-C; Cytosar; DepoCyt; Cytosine Arabinosine Hydrochloride

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Clofarabine, Idarubicin, and Cytarabine

  MTD is highest dose level in which \<2 patients of 6 develop first cycle dose limiting toxicities (DLT). Toxicity defined as any treatment-related grade 3 or greater non-hematological toxicities.

  28 days

Secondary Outcomes (3)

• Response Rates of Clofarabine, Idarubicin, and Cytarabine (CIA) Versus Fludarabine, Idarubicin, and Cytarabine (FLAI)

  12 months

• Event-Free Survival (EFS) at 2 Years

  Up to 2 years or until relapse/death

• Overall Survival

  up to 2 years

Study Arms (3)

Clofarabine + Idarubicin + Cytarabine

EXPERIMENTAL

Phase I: Clofarabine Starting dose 15 mg/m2 by vein for 5 days (days 1-5) + Idarubicin 10 mg/m2 by vein on day 1-3 + Cytarabine 1 g/m2 by vein on day 1-5.

Drug: Clofarabine; Drug: Idarubicin; Drug: Cytarabine; Drug: Fludarabine

Group 1 CIA

EXPERIMENTAL

Phase II, Group 1 CIA (Clofarabine + Idarubicin + Cytarabine): Clofarabine Maximum Tolerated Dose (MTD) based on Phase I by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5.

Drug: Clofarabine; Drug: Idarubicin; Drug: Cytarabine

Group 2 FLAI

EXPERIMENTAL

Phase II, Group 2 FLAI (Fludarabine + Idarubicin + Cytarabine): Fludarabine 30 mg/m2 by vein on days 1-5; Idarubicin 10 mg/m2 by vein on days 1-3; Cytarabine 1 g/m2 by vein on days 1-5.

Drug: Idarubicin; Drug: Cytarabine; Drug: Fludarabine

Interventions

Clofarabine DRUG

Phase I: 15 mg/m2 by vein (IV) daily for 5 days of a 28 day cycle. Phase II: Clofarabine (dose selected based on Phase I portion) by vein over approximately 1 hour daily for 5 days (days 1-5) for a 28 day cycle.

Also known as: Clofarex, Clolar

Clofarabine + Idarubicin + Cytarabine; Group 1 CIA

Idarubicin DRUG

10 mg/m2 by vein over approximately 30 minutes daily for 3 days (days 1-3) of a 28 day cycle.

Also known as: Idamycin

Clofarabine + Idarubicin + Cytarabine; Group 1 CIA; Group 2 FLAI

Cytarabine DRUG

1 g/m2 by vein over approximately 2 hours daily for 5 days (days 1-5) for a 28 day cycle.

Also known as: Ara-C, Cytosar, DepoCyt, Cytosine Arabinosine Hydrochloride

Clofarabine + Idarubicin + Cytarabine; Group 1 CIA; Group 2 FLAI

Fludarabine DRUG

30 mg/m2 by vein over approximately 30 minutes daily for 5 days (days 1-5).

Also known as: Fludara

Clofarabine + Idarubicin + Cytarabine; Group 2 FLAI

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Sign an Institutional Review Board (IRB)-approved informed consent document.
• Age 18 to 60. Patients above the age of 60 only with principal investigator (PI) approval
• Diagnosis of newly diagnosed AML \[other than acute promyelocytic leukemia (APL)\] or high-risk (intermediate-2 or high by International Prostate Symptom Score (IPSS) or \> 10% blasts, including CMML) MDS. Prior therapy with hydrea and the use of a single or a two day dose of cytarabine (up to 3 g/m2) for emergency use up to 24 hours prior to start of study therapy is allowed. Prior therapy for MDS or other AHD is not allowed.
• Eastern Cooperative Oncology Group (ECOG) performance status of \</= 3 at study entry.
• Organ function as defined below (unless due to leukemia): Serum creatinine \</= 3 mg/dL Total bilirubin \</= 2.5 mg/dL , Alanine aminotransferase (ALT) (SGPT) \</= 3 \* upper limit of normal (ULN) or \</= 5 \* ULN if related to disease.
• Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days and must agree to practice acceptable contraceptive methods. Men must agree not to father a child and agree to use a condom if his partner is of child bearing potential.
• Cardiac ejection fraction \>/= 40% (by either cardiac echo or multiple gated acquisition scan (MUGA) scan). Documentation of recent (\</= 6 months from screening) outside reports is acceptable.

You may not qualify if:

• Breast feeding females
• Patients with uncontrolled active infections (viral, bacterial, and fungal are not eligible).
• Patients with active secondary malignancy will not be eligible.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Morita K, Kantarjian HM, Wang F, Yan Y, Bueso-Ramos C, Sasaki K, Issa GC, Wang S, Jorgensen J, Song X, Zhang J, Tippen S, Thornton R, Coyle M, Little L, Gumbs C, Pemmaraju N, Daver N, DiNardo CD, Konopleva M, Andreeff M, Ravandi F, Cortes JE, Kadia T, Jabbour E, Garcia-Manero G, Patel KP, Futreal PA, Takahashi K. Clearance of Somatic Mutations at Remission and the Risk of Relapse in Acute Myeloid Leukemia. J Clin Oncol. 2018 Jun 20;36(18):1788-1797. doi: 10.1200/JCO.2017.77.6757. Epub 2018 Apr 27.

  PMID: 29702001 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Acute; Recurrence

Interventions

Clofarabine; Idarubicin; Cytarabine; fludarabine; fludarabine phosphate

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Jabbour,Elias Joseph, M.D./Associate Professor
• Organization: The University of Texas M D Anderson Cancer Center

CR_Study_Registration@mdanderson.org

713-792-4764

Study Officials

• Elias Jabbour, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2011
• First Posted: February 3, 2011
• Study Start: February 2, 2011
• Primary Completion: June 28, 2017
• Study Completion: June 28, 2017
• Last Updated: February 24, 2020
• Results First Posted: February 24, 2020

Record last verified: 2020-02

Locations

US (1)