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Acute Lymphoblastic LeukemiaPhase 2NCT00390793

Combination Chemotherapy and Dasatinib in Treating Participants With Philadelphia Positive or BCR-ABL Positive Acute Lymphoblastic Leukemia.

A Phase 2 study testing Cyclophosphamide, Cytarabine and Dasatinib in people with Acute Lymphoblastic Leukemia and BCR-ABL1 Fusion Protein Expression, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This phase II trial studies how well combination chemotherapy and dasatinib works in treating participants with Philadelphia-positive or B-cell receptor-ABL positive acute lymphoblastic leukemia. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cyclophosphamide, Cytarabine and Dasatinib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
107 participants
Where
1 siteUnited States
Study dates
28 Sep 2006to 2 Feb 2024
Phase
Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of one of the following: Previously untreated Ph-positive acute lymphoblastic leukemia (ALL) (either t(9;22) and/or BCR-ABL positive) (includes patients initiated on first course of hyper-CVAD before cytogenetics known). These groups will be analyzed separately. After 1-2 courses of chemotherapy with or without imatinib mesylate (Gleevec). If they achieved complete response (CR), they are assessable only for event-free and overall survival, or if they failed to achieve CR, they are assessable for CR, event-free, and overall survival. Patients with relapsed Ph-positive ALL or lymphoid blast phase of chronic myelogenous leukemia (CML)
  • Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
  • Adequate liver function (bilirubin less than or equal to 3.0 mg/dl, unless considered due to tumor), and renal function (creatinine less than or equal to 3.0 mg/dl, unless considered due to tumor)
  • Adequate cardiac function as assessed clinically
  • Signed informed consent

Who cannot join

  • Active serious infection not controlled by oral or intravenous antibiotics
  • Treatment with any investigational antileukemic agents or chemotherapy agents in the last 7 days before study entry, unless full recovery from side effects has occurred or patient has rapidly progressive disease judged to be life-threatening by the investigator
  • Active secondary malignancy other than skin cancer (e.g., basal cell carcinoma or squamous cell carcinoma) that in the investigator's opinion will shorten survival to less than 1 year
  • Active grade III-V cardiac failure as defined by the New York Heart Association criteria. Uncontrolled angina, or myocardial infarction (MI) within 6 months. Diagnosed or suspected congenital long QT syndrome. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes). Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (> 470 msec). Patients currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes (unless these can be changed to acceptable alternatives)
  • Prior history of treatment with dasatinib
  • Pregnant and lactating women will not be eligible; women of childbearing potential should have a negative pregnancy test prior to entering on the study and be willing to practice methods of contraception. Women do not have childbearing potential if they have had a hysterectomy or are postmenopausal without menses for 12 months. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control
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  • History of significant bleeding disorder unrelated to cancer, including:
  • Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
  • Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
  • Patients with documented significant pleural or pericardial effusions unless they are thought to be secondary to their leukemia

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase II Study of Combination of Hyper-CVAD and Dasatinib in Patients With Philadelphia (Ph) Chromosome Positive and/or BCR-ABL Positive Acute Lymphoblastic Leukemia (ALL)

This phase II trial studies how well combination chemotherapy and dasatinib works in treating participants with Philadelphia-positive or B-cell receptor-ABL positive acute lymphoblastic leukemia. Drugs used in chemotherapy, such as cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving chemotherapy in combination with dasatinib may work better in treating participants with Philadelphia-positive or BCR-ABL positive acute lymphoblastic leukemia.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the clinical efficacy (event-free survival) of an intensive short-term chemotherapy regimen (Hyper- cyclophosphamide, vincristine, doxorubicin, dexamethasone [CVAD] program) given in combination with the tyrosine kinase inhibitor dasatinib for Philadelphia (Ph)-positive and/or B-cell receptor BCR-ABL-positive acute lymphoblastic leukemia (ALL).

II. To evaluate other clinical efficacy (overall response rate and survival) and safety of an intensive short-term chemotherapy regimen (Hyper-CVAD program) given in combination with the tyrosine kinase inhibitor dasatinib for Philadelphia (Ph)-positive and/or BCR-ABL-positive acute lymphoblastic leukemia (ALL).

OUTLINE:

HYPER-CVAD THERAPY: Participants receive cyclophosphamide intravenously (IV) twice daily (BID) over 3 hours on days 1-3, vincristine IV over 30 minutes on days 4 and 11, and doxorubicin IV over 24-48 hours on day 4. Participants also receive dexamethasone orally (PO) or IV over 30 minutes on days 1-4 and 11-14, and dasatinib PO once daily (QD) on days 1-14 of course 1 and on days 1-21 for subsequent courses. Courses repeat every 21 days for up to 4 odd courses (1, 3, 5, and 7) in the absence of disease progression or unacceptable toxicity.

METHOTREXATE PLUS CYTARABINE: Participants receive methotrexate IV over 24 hours on day 1, dasatinib PO on days 1-21, and cytarabine IV BID over 2 hours on days 2 and 3. Courses repeat every 21 days for up to 4 even courses (2, 4, 6, and 8) in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Participants receive vincristine IV over 30 minutes on day 1, prednisone PO on days 1-5, and dasatinib PO BID. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. During courses 6 and 13, participants may receive an additional course of hyper-CVAD therapy.

After completion of study treatment, participants are followed for up to 12 months.

Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Blast Crisis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • CytarabineDrug

    Also called .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone

    Given IV or IT

  • DasatinibDrug

    Also called BMS-354825, Sprycel

    Given PO

  • DexamethasoneDrug

    Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex

    Given IV or PO

  • DoxorubicinDrug

    Also called Adriablastin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin

    Given IV

  • MethotrexateDrug

    Also called Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate

    Given IV or IT

  • PrednisoneDrug

    Also called .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl

    Given PO

  • VincristineDrug

    Also called LEUROCRISTINE, VCR, Vincrystine

    Given IV

Study groups in NCT00390793
Study groupRoleWhat they receive
Treatment (chemotherapy, dasatinib)ExperimentalSee detailed description in outline.
Receives: Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dasatinib; Drug: Dexamethasone; Drug: Doxorubicin; Drug: Methotrexate; Drug: Prednisone; Drug: Vincristine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Event-free Survival Rate (EFS)

    Time from date of treatment start until the date of failure or death from any cause.

    Measured: Up to 17 years, 4 months, 2 days

  2. Disease-free Survival

    Time from date of treatment start until the date of first objective documentation of disease-relapse.

    Measured: Up to 17 years, 4 months, 2 days

Secondary outcomes (2)

  1. Participants With a Response

    Participants achieving complete remission (CR) + partial remission (PR) - Complete Remission (CR): Normalization of the peripheral blood and bone marrow with 5% or less blasts in normocellular or hypercellular marrow with a granulocyte count of 1 x 10^9/L or above, and platelet count of 100 x 10^9/L. Complete resolution of all sites of extramedullary disease is required for CR.

    Measured: Up to 17 years, 4 months, 2 days

  2. Overall Survival

    Time from date of treatment start until date of death due to any cause or last Follow-up.

    Measured: Up to 17 years, 4 months, 2 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Oct 2006 (estimated)
  2. Study start28 Sep 2006
  3. Primary completion2 Feb 2024
  4. Study completion2 Feb 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
107 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00390793
Sponsor's protocol ID
2006-0478
Other IDs
NCI-2018-01846, 2006-0478
Status last verified
Jan 2025
First submitted
18 Oct 2006
Last updated
17 Feb 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Ravandi F, O'Brien S, Thomas D, Faderl S, Jones D, Garris R, Dara S, Jorgensen J, Kebriaei P, Champlin R, Borthakur G, Burger J, Ferrajoli A, Garcia-Manero G, Wierda W, Cortes J, Kantarjian H. First report of phase 2 study of dasatinib with hyper-CVAD for the frontline treatment of patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia. Blood. 2010 Sep 23;116(12):2070-7. doi: 10.1182/blood-2009-12-261586. Epub 2010 May 13.

    PubMed 20466853

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