CLAG Gleevec in Relapsed or Refractory Acute Myeloid Leukemia (AML)

NCT00955916 | Completed Phase 2 Results DMC

• 2 other identifiers: MCC-15787CSTI571AUS235
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to find out what effects (good and bad) Gleevec® (Imatinib mesylate) combined with chemotherapy has on participants and their acute myeloid leukemia.

Conditions

Leukemia

Keywords

relapsed; refractory; acute; myeloid; AML; CML; blast crisis

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  Overall Response Rate: Morphologic Complete Remission (CR) + Morphologic Complete Remission with incomplete blood count recovery (CRi) for evaluable participants. CR - Bone Marrow: \< 5% blasts without Auer rods with at least 20% cellularity with maturation of all cell lines, No presence of unique phenotype by flow cytometry identical to what was found in the pretreatment specimen, No persistent dysplasia; Peripheral: normal blood counts, absolute neutrophil count (ANC) \> 1.0 k/μl and platelets \> 100 k/μl ANC \> 1.0 k/μl and platelets \> 100 k/μl (Peripheral blood counts documenting recovery can be utilized within 4 weeks of the bone marrow); No evidence of extramedullary leukemia. CRi - All CR criteria are met except for residual Neutropenia \<1.0 x 10\^9/L platelets \< 100 k/μl.

  8 weeks per participant

Secondary Outcomes (2)

• Median Progression Free Survival (PFS)

  Up to 3 years

• Median Overall Survival (OS)

  Up to 3 years

Study Arms (1)

CLAG Regimen with Gleevec®

EXPERIMENTAL

Combined chemotherapy treatment (CLAG regimen) with Gleevec® (imatinib mesylate).

Drug: CLAG Regimen; Drug: Gleevec®

Interventions

CLAG Regimen DRUG

The CLAG regimen consisted of: Cladribine, 5 mg/m\^2 administered via 2 hour IV daily for 5 consecutive days starting on day 2; Cytarabine, 2 mg/m\^2 administered through a 4 hour IV starting 2 hours after the ignition of Cladribine for 5 days starting on day 2; granulocyte colony-stimulating factor (G-CSF): 300 mcg subcutaneous (SC) for 6 days starting 12-24 hours (Day 1) before the first dose of Cladribine.

Also known as: cladribine, cytarabine, neupogen

CLAG Regimen with Gleevec®

Gleevec® DRUG

Imatinib mesylate 400 mg orally twice daily was administered on day 2 to day 15. Re-induction was allowed if participant had partial response (PR).

Also known as: imatinib mesylate

CLAG Regimen with Gleevec®

Eligibility Criteria

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

You may qualify if:

• Men and Women of all ethnic groups whose age is ≥ 18 years old.
• Diagnosis of AML or CML blast crisis, according to World Health Organization (WHO) criteria, except acute promyelocytic leukemia AML-M3 French-American-British (FAB) subgroup. A documentation of relapse is required by a bone marrow/aspirate within 4 weeks of registration.
• Refractory or Relapsed AML. Refractory AML is defined as failure to achieve CR after 2 cycles of induction chemotherapy or persistent (\>40%) bone marrow blasts after one cycle of chemotherapy induction.
• Relapsed AML is defined as any evidence of disease recurrence after achieving complete response (CR) (more than 5% myeloblasts). Early relapse is defined as that occurring within 12 months and late relapse is defines as that occurring after 12 months.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Patients must sign a written informed consent.
• Females of childbearing potential (FOCP) must not be pregnant or actively nursing a child. They must have a negative pregnancy test 7 days before initiation of study drug administration
• Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
• Male and females of reproductive potential must agree to employ an effective barrier method of birth control throughout the duration of the trial and for 3 months following study medication discontinuation.
• Prior allogeneic or autologous stem cell transplantation is allowed.

You may not qualify if:

• Abnormal Kidney Functions: creatinine ≥2.5 mg/dL.
• Abnormal Liver Functions: Bilirubin more 3 mg/dL, transaminases (AST/ALT) more than 2.5 times the institutional upper limits of normal (IULN).
• Systemic active infection, unless controlled on active therapy.
• Patients with Grade III/IV cardiac problems as defined by the New York Heart Association (NYHA) Criteria ( i.e., congestive heart failure, myocardial infarction within 6 months of the study), or ejection fraction (EF)\< 30%.
• Patient has known chronic liver disease (i.e., chronic active hepatitis, hepatitis B, hepatitis C, and cirrhosis).
• Patient has known diagnosis of human immunodeficiency virus (HIV) infection.
• History of other malignancy, except non-melanotic skin cancers or no disease recurrence/progression for more than 2 years.
• Patients that have received investigational agents within 1 month of study entry.
• History of allergic reaction attributed to compounds of similar chemical or biologic composition to Gleevec or any component of the CLAG regimen
• Prior therapy with CLAG chemotherapy regimen
• Any adverse event attributable to previous chemotherapy regimen must be resolved to grade 1 or less at time of registration.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Novartis: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Leukemia; Recurrence; Blast Crisis

Interventions

Cladribine; Cytarabine; Filgrastim; Imatinib Mesylate

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease

Intervention Hierarchy (Ancestors)

2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines

Results Point of Contact

• Title: Rami Komrokji, M.D.
• Organization: H. Lee Moffitt Cancer Center and Research Institute

rami.komrokji@moffitt.org

813-745-4291

Study Officials

• Rami Komrokji, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2009
• First Posted: August 10, 2009
• Study Start: August 1, 2009
• Primary Completion: December 1, 2012
• Study Completion: May 1, 2014
• Last Updated: June 27, 2014
• Results First Posted: January 14, 2014

Record last verified: 2014-06

Locations

US (1)