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Clofarabine and Daunorubicin in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

Primary Purpose

Leukemia

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
clofarabine
daunorubicin hydrochloride
cytogenetic analysis
protein expression analysis
immunologic technique
pharmacological study
Sponsored by
Roswell Park Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring adult erythroleukemia (M6a), adult pure erythroid leukemia (M6b), adult acute megakaryoblastic leukemia (M7), adult acute minimally differentiated myeloid leukemia (M0), adult acute monoblastic leukemia (M5a), adult acute monocytic leukemia (M5b), adult acute myeloblastic leukemia with maturation (M2), adult acute myeloblastic leukemia without maturation (M1), adult acute myelomonocytic leukemia (M4), untreated adult acute myeloid leukemia, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), secondary acute myeloid leukemia

Eligibility Criteria

60 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS:

  • Newly diagnosed acute myeloid leukemia

    • At least 10% blasts in the peripheral blood
  • De novo or secondary disease
  • No acute promyelocytic leukemia with t[15;17] or any other variant
  • No clinical evidence of CNS disease

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN
  • Alkaline phosphatase ≤ 2.5 times ULN
  • LVEF ≥ 45%
  • Estimated glomerular filtration rate ≥ 50 mL/min
  • Not pregnant or nursing
  • Fertile patients must use effective barrier contraception during and for at least 6 months following study treatment
  • No known HIV positivity
  • Able to comply with study procedures and follow-up examinations
  • No psychiatric disorders that would interfere with consent, study participation, or follow-up
  • No uncontrolled systemic fungal, bacterial, viral, or other infection (i.e., exhibiting ongoing signs/symptoms related to the infection and without improvement despite appropriate antibiotics or other treatment)
  • No history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo induction therapy with both agents

  • No other malignancy, unless disease-free for at least 3 years following curative intent therapy

    • Nonmelanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are allowed if definitive treatment for the condition has been completed
    • Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed
  • No other severe concurrent disease

PRIOR CONCURRENT THERAPY:

  • No other concurrent systemic antileukemic therapy (standard or investigational)
  • No concurrent cytotoxic therapy or investigational therapy
  • No concurrent alternative medications (e.g., herbal or botanical for anticancer purposes)

  • No prior chemotherapy

    • Prior hydroxyurea allowed

Sites / Locations

  • Roswell Park Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Clorafarbine with daunorubicin

Arm Description

Patients receive clofarabine IV over 1 hour on days 1-5 and daunorubicin hydrochloride IV over 5 minutes on days 1, 3, and 5.

Outcomes

Primary Outcome Measures

Complete Remission (CR)
Complete Response/Remission (CR) was defined on morphologic criteria at a single response assessment as follows: A bone marrow aspirate or biopsy of < 5% blasts, with evidence of normal hematopoiesis; Absence of Auer rods in the blast that are present; Absence of extramedullary disease [imaging required only if obtained pretreatment for known site(s) of disease]; If applicable and available, absence of a unique phenotype determined at the pretreatment specimen, as assessed by immunophenotyping; Recovery of peripheral counts (platelets ≥100x109/L, and ANC ≥1.0x109/L). Peripheral count recovery must be documented no earlier than 7 days prior to, and no later than 14 days following, the bone marrow assessment that provides evidence of the CR. Complete Response/Remission without platelet recovery (CRp) was defined as all criteria for CR except for thrombocytopenia (platelet count ≥75x109/L).

Secondary Outcome Measures

Disease-free Survival
Disease-free survival was defined as time from first objective documentation of CR or CRp until the date of first objective documentation of disease relapse or death due to any cause, whichever occurs first.
Overall Survival
Overall survival was defined as time from date of treatment initiation until date of death due to any cause.
Differences in Disease-free and Overall Survival Between Patients Whose Cells do or do Not Demonstrate Apoptosis Following Clofarabine and Daunorubicin Hydrochloride Therapy
Difference in Disease-free and Overall Survival According to p53R2 Protein Sizes
Difference in Disease-free and Overall Survival According to Multi-drug Resistance Protein Expression
Difference in Disease-free and Overall Survival Based on Clofarabine Triphosphate Levels
A Preliminary Relationship Between Treatment Outcome and Biologic Parameters

Full Information

First Posted
December 23, 2008
Last Updated
July 7, 2016
Sponsor
Roswell Park Cancer Institute
Collaborators
Genzyme, a Sanofi Company
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1. Study Identification

Unique Protocol Identification Number
NCT00814164
Brief Title
Clofarabine and Daunorubicin in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia
Official Title
A Phase II Study Evaluating Mechanisms of Resistance Following Treatment With Clofarabine and Daunorubicin in Newly Diagnosed Adult Acute Myeloid Leukemia Patients > or = to 60 Years Old
Study Type
Interventional

2. Study Status

Record Verification Date
July 2016
Overall Recruitment Status
Terminated
Why Stopped
Sponsor withdrew support
Study Start Date
December 2008 (undefined)
Primary Completion Date
June 2013 (Actual)
Study Completion Date
August 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Roswell Park Cancer Institute
Collaborators
Genzyme, a Sanofi Company

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RATIONALE: Drugs used in chemotherapy, such as clofarabine and daunorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving clofarabine together with daunorubicin may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving clofarabine together with daunorubicin works in treating older patients with newly diagnosed acute myeloid leukemia.
Detailed Description
OBJECTIVES: Primary Study complete response (CR) and CR without platelet recovery (CRp) following treatment with clofarabine and daunorubicin hydrochloride in older patients with newly diagnosed acute myeloid leukemia. Secondary Study disease-free and overall survival of these patients following treatment with this regimen. Compare disease-free and overall survival of patients whose cells do or do not demonstrate apoptosis following treatment with this regimen. OUTLINE: Induction therapy: Patients receive clofarabine IV over 1 hour on days 1-5 and daunorubicin hydrochloride IV over 5 minutes on days 1, 3, and 5. Patients are assessed after induction course 1. Patients with ≥ 5% blasts in bone marrow may receive another course of induction therapy beginning between 28-84 days after initiation of course 1. Patients who achieve complete remission (CR) or CR without platelet recovery (CRp) (after 1 or 2 courses of induction therapy) proceed to consolidation therapy. Consolidation therapy: Beginning between 28 -84 days after initiation of last course of induction therapy, patients receive clofarabine IV over 1 hour on days 1-3 and daunorubicin hydrochloride IV over 5 minutes on days 1 and 3. Patients may receive a second course of consolidation therapy beginning between 28-84 days of consolidation course 1. Blood and bone marrow samples are collected periodically to assess response and for pharmacokinetic, cytogenetic, immunophenotyping, and molecular analyses. After completion of study treatment, patients are followed for at least 2 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia
Keywords
adult erythroleukemia (M6a), adult pure erythroid leukemia (M6b), adult acute megakaryoblastic leukemia (M7), adult acute minimally differentiated myeloid leukemia (M0), adult acute monoblastic leukemia (M5a), adult acute monocytic leukemia (M5b), adult acute myeloblastic leukemia with maturation (M2), adult acute myeloblastic leukemia without maturation (M1), adult acute myelomonocytic leukemia (M4), untreated adult acute myeloid leukemia, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), secondary acute myeloid leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Clorafarbine with daunorubicin
Arm Type
Experimental
Arm Description
Patients receive clofarabine IV over 1 hour on days 1-5 and daunorubicin hydrochloride IV over 5 minutes on days 1, 3, and 5.
Intervention Type
Drug
Intervention Name(s)
clofarabine
Intervention Description
IV
Intervention Type
Drug
Intervention Name(s)
daunorubicin hydrochloride
Intervention Description
IV
Intervention Type
Genetic
Intervention Name(s)
cytogenetic analysis
Intervention Description
Correlative study
Intervention Type
Genetic
Intervention Name(s)
protein expression analysis
Intervention Description
Correlative Study
Intervention Type
Other
Intervention Name(s)
immunologic technique
Intervention Description
Correlative Study
Intervention Type
Other
Intervention Name(s)
pharmacological study
Intervention Description
Correlative Study
Primary Outcome Measure Information:
Title
Complete Remission (CR)
Description
Complete Response/Remission (CR) was defined on morphologic criteria at a single response assessment as follows: A bone marrow aspirate or biopsy of < 5% blasts, with evidence of normal hematopoiesis; Absence of Auer rods in the blast that are present; Absence of extramedullary disease [imaging required only if obtained pretreatment for known site(s) of disease]; If applicable and available, absence of a unique phenotype determined at the pretreatment specimen, as assessed by immunophenotyping; Recovery of peripheral counts (platelets ≥100x109/L, and ANC ≥1.0x109/L). Peripheral count recovery must be documented no earlier than 7 days prior to, and no later than 14 days following, the bone marrow assessment that provides evidence of the CR. Complete Response/Remission without platelet recovery (CRp) was defined as all criteria for CR except for thrombocytopenia (platelet count ≥75x109/L).
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Disease-free Survival
Description
Disease-free survival was defined as time from first objective documentation of CR or CRp until the date of first objective documentation of disease relapse or death due to any cause, whichever occurs first.
Time Frame
5 years
Title
Overall Survival
Description
Overall survival was defined as time from date of treatment initiation until date of death due to any cause.
Time Frame
4 years
Title
Differences in Disease-free and Overall Survival Between Patients Whose Cells do or do Not Demonstrate Apoptosis Following Clofarabine and Daunorubicin Hydrochloride Therapy
Time Frame
4 years
Title
Difference in Disease-free and Overall Survival According to p53R2 Protein Sizes
Time Frame
4 years
Title
Difference in Disease-free and Overall Survival According to Multi-drug Resistance Protein Expression
Time Frame
4 years
Title
Difference in Disease-free and Overall Survival Based on Clofarabine Triphosphate Levels
Time Frame
4 years
Title
A Preliminary Relationship Between Treatment Outcome and Biologic Parameters
Time Frame
4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Newly diagnosed acute myeloid leukemia At least 10% blasts in the peripheral blood De novo or secondary disease No acute promyelocytic leukemia with t[15;17] or any other variant No clinical evidence of CNS disease PATIENT CHARACTERISTICS: ECOG performance status 0-2 Serum bilirubin ≤ 1.5 times upper limit of normal (ULN) AST and ALT ≤ 2.5 times ULN Alkaline phosphatase ≤ 2.5 times ULN LVEF ≥ 45% Estimated glomerular filtration rate ≥ 50 mL/min Not pregnant or nursing Fertile patients must use effective barrier contraception during and for at least 6 months following study treatment No known HIV positivity Able to comply with study procedures and follow-up examinations No psychiatric disorders that would interfere with consent, study participation, or follow-up No uncontrolled systemic fungal, bacterial, viral, or other infection (i.e., exhibiting ongoing signs/symptoms related to the infection and without improvement despite appropriate antibiotics or other treatment) No history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo induction therapy with both agents No other malignancy, unless disease-free for at least 3 years following curative intent therapy Nonmelanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are allowed if definitive treatment for the condition has been completed Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed No other severe concurrent disease PRIOR CONCURRENT THERAPY: No other concurrent systemic antileukemic therapy (standard or investigational) No concurrent cytotoxic therapy or investigational therapy No concurrent alternative medications (e.g., herbal or botanical for anticancer purposes) No prior chemotherapy Prior hydroxyurea allowed
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Meir Wetzler, MD
Organizational Affiliation
Roswell Park Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263-0001
Country
United States

12. IPD Sharing Statement

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Clofarabine and Daunorubicin in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

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