AzTrials
AzTrials

LeukemiaPhase 3NCT00005823

Intensive Compared With Nonintensive Chemotherapy in Treating Older Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome

A Phase 3 study testing cytarabine, daunorubicin hydrochloride and etoposide in people with Leukemia and Myelodysplastic Syndromes, run by Leukemia Research Fund at 3 sites in United Kingdom.

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

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. It is not yet known if stronger doses of chemotherapy given over a longer period of time are as well tolerated or as effective as less intensive chemotherapy. Read more about this study

Who is it for?
Ages 60 years and older
What is being tested?
cytarabine, daunorubicin hydrochloride and etoposide
How many people
2,000 participants
Where
3 sitesUnited Kingdom
Study dates
Dec 1998to Dec 2007
Phase
Phase 3
Are there results?
None posted in the registry

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

DISEASE CHARACTERISTICS:

  • Acute myeloid leukemia (de novo or secondary) OR
  • Myelodysplastic syndrome
  • More than 10% myeloblasts in the bone marrow
  • Refractory anemia with excess blasts
  • Refractory anemia with excess blasts in transformation
  • Chronic myelomonocytic leukemia
  • No acute promyelocytic leukemia (FAB type M3)
  • No blastic phase chronic myeloid leukemia

PATIENT CHARACTERISTICS:

Age:

  • 60 and over (younger patients allowed if intensive chemotherapy not indicated)

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • Not specified

Hepatic:

  • No liver function test ≥ 2 times normal (for non-intensive therapy arm)

Renal:

  • Not specified

Cardiovascular:

  • No myocardial infarction within past 6 months in patients receiving daunorubicin or PSC 833

Other:

  • No other concurrent active malignancy

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • No prior cytotoxic chemotherapy for leukemia

Endocrine therapy:

  • Not specified

Radiotherapy:

  • Not specified

Surgery:

  • Not specified

Trial locations and contacts

3 sites in 1 country.

United Kingdom3 sites

  • Queen Elizabeth Hospital at University of Birmingham

    Birmingham, England, B15 2RR

  • University Hospital of Wales

    Cardiff, Wales, CF14 4XN

  • University College Hospital

    London, England, WC1E 6AU

Other trials in United Kingdom

About this study

Official title: A Randomized Trial for Patients With Acute Myeloid Leukemia or High Risk Myelodysplatic Syndrome Aged 60 or Over

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. It is not yet known if stronger doses of chemotherapy given over a longer period of time are as well tolerated or as effective as less intensive chemotherapy.

PURPOSE: This randomized phase III trial is studying intensive regimens of chemotherapy to see how well they work compared to nonintensive regimens of chemotherapy in treating older patients with acute myeloid leukemia or myelodysplastic syndrome.

Read the detailed description

OBJECTIVES:

  • Compare the response rate, survival, quality of life, and supportive care requirements with intensive versus nonintensive chemotherapy in older patients with acute myeloid leukemia or high risk myelodysplastic syndrome.
  • Compare response achievement, response duration, survival, toxicity and supportive care requirements with differing doses of daunorubicin and cytarabine in these patients receiving intensive chemotherapy.
  • Determine the efficacy of PSC 833 in enhancing the effects of daunorubicin in these patients receiving intensive chemotherapy.
  • Compare relapse rate, deaths in complete remission, disease free survival, and survival with short versus long intensive chemotherapy in these patients.
  • Compare response achievement, response duration, survival, toxicity, quality of life, and resource use with hydroxyurea versus cytarabine in these patients receiving low dose chemotherapy.
  • Determine response achievement, response duration, survival, toxicity, quality of life, and supportive care requirements with the addition of tretinoin to the nonintensive chemotherapy in these patients.
  • Assess the correlation between P-gp and BCL-2 in family members and treatment outcomes and other prognostic factors in these patients with these treatment regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized or electively assigned to either intensive or nonintensive chemotherapy*.

Intensive chemotherapy

  • Induction therapy: Patients are randomized to 1 of 6 treatment arms. Patients receive 2 courses of chemotherapy comprising 1 of 2 daunorubicin doses, 1 of 2 cytarabine doses, thioguanine, and with or without PSC 833.

Patients receive daunorubicin IV once daily on days 1-3 with cytarabine IV twice daily and oral thioguanine once daily on days 1-10 during course 1. Treatment repeats in approximately 31 days as in course 1 except cytarabine and thioguanine are given only on days 1-8.

  • Arm I: Patients receive higher dose of daunorubicin, lower dose of cytarabine, and thioguanine.
  • Arm II: Patients receive higher dose of daunorubicin, higher dose of cytarabine, and thioguanine.
  • Arm III: Patients receive lower dose of daunorubicin, lower dose of cytarabine, and thioguanine.
  • Arm IV: Patients receive lower dose of daunorubicin, higher dose of cytarabine, and thioguanine.
  • Arm V: Patients receive treatment as in arm III in combination with continuous infusion of PSC 833 beginning day 1.
  • Arm VI: Patients receive treatment as in arm IV in combination with continuous infusion of PSC 833 beginning on day 1.

Patients with refractory disease after the first course of induction chemotherapy may continue with the intensive protocol arm or enter the nonintensive arm*. Patients who do not achieve complete remission after completion of induction chemotherapy are removed from study. Patients in complete remission after induction therapy receive consolidation therapy.

  • Consolidation therapy: Patients in complete remission after induction are randomized to either short or long consolidation.
  • Short consolidation: Patients receive mitoxantrone IV on days 1-3 and cytarabine IV over 2 hours twice daily on days 1-3.
  • Long consolidation: Patients complete short consolidation and then receive idarubicin IV over 5 minutes once daily on days 1 and 3, cytarabine IV over 2 hours twice daily and etoposide IV over 1 hour once daily on days 1-3.

Non-intensive chemotherapy*

  • Patients are randomized to 1 of 4 treatment arms.
  • Arm I: Patients receive oral hydroxyurea as necessary to control WBC count until treatment failure.
  • Arm II: Patients receive hydroxyurea as in arm I and oral tretinoin daily for up to 16 weeks.
  • Arm III: Patients receive low dose cytarabine subcutaneously twice daily on days 1-10 every 28 days for a minimum of 4 courses.
  • Arm IV: Patients receive cytarabine as in arm III plus oral tretinoin daily for up to 16 weeks.

NOTE: *Patients with liver function test > 2 times upper limit of normal are not eligible for nonintensive randomization

Quality of life is assessed at study entry, and then at 1, 3, and 6 months.

Patients are followed at one year.

PROJECTED ACCRUAL: Approximately 2,000 patients (1,200 to intensive arm and 800 to nonintensive arm) will be accrued for this study over 5 years.

Being tested
cytarabine, daunorubicin hydrochloride, etoposide, hydroxyurea, idarubicin
Keywords
untreated adult acute myeloid leukemia, adult acute erythroid leukemia (M6), adult acute myeloblastic leukemia without maturation (M1), adult acute myeloblastic leukemia with maturation (M2), adult acute myelomonocytic leukemia (M4), adult acute monoblastic leukemia (M5a), adult acute megakaryoblastic leukemia (M7), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, chronic myelomonocytic leukemia, secondary acute myeloid leukemia, de novo myelodysplastic syndromes, adult acute monocytic leukemia (M5b), secondary myelodysplastic syndromes, adult acute minimally differentiated myeloid leukemia (M0), atypical chronic myeloid leukemia, BCR-ABL1 negative, myelodysplastic/myeloproliferative neoplasm, unclassifiable, 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)
Medical subject headings
Leukemia, Myelodysplastic Syndromes, Myelodysplastic-Myeloproliferative Diseases, Leukemia, Erythroblastic, Acute, Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Acute, Leukemia, Monocytic, Acute, Leukemia, Megakaryoblastic, Acute

What participants receive

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

  • cytarabineDrug

  • daunorubicin hydrochlorideDrug

  • etoposideDrug

  • hydroxyureaDrug

  • idarubicinDrug

  • mitoxantrone hydrochlorideDrug

  • thioguanineDrug

  • tretinoinDrug

  • valspodarDrug

What is being measured

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

  1. Survival

  2. Response achievement

  3. Response duration

Secondary outcomes (3)

  1. Toxicity by WHO Toxicity Grading after each treatment course

  2. Quality of life EORTC QLQ-C30 at 3 days, 1 month, 3 months, and 6 months from study entry

  3. Resource use (use of blood products, antibiotics and days in hospital) after each treatment course

Timeline

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

  1. First posted27 Jan 2003 (estimated)
  2. Study startDec 1998
  3. Study completionDec 2007

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 3
Primary purpose
Treatment
Allocation
Randomised
Enrolment
2,000 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00005823
Sponsor's protocol ID
CDR0000067831
Other IDs
LRF-AML14, EU-20016, ISRCTN62207270
Status last verified
Sep 2006
First submitted
2 Jun 2000
Last updated
18 Dec 2013
Results posted
No

Publications

  • Seedhouse CH, Grundy M, White P, Li Y, Fisher J, Yakunina D, Moorman AV, Hoy T, Russell N, Burnett A, Pallis M; National Cancer Research Network. Sequential influences of leukemia-specific and genetic factors on p-glycoprotein expression in blasts from 817 patients entered into the National Cancer Research Network acute myeloid leukemia 14 and 15 trials. Clin Cancer Res. 2007 Dec 1;13(23):7059-66. doi: 10.1158/1078-0432.CCR-07-1484.

    PubMed 18056183

  • Burnett AK, Milligan D, Hills RK, et al.: Does all-transretinoic acid (ATRA) have a role in non-APL acute myeloid leukaemia? Results from 1666 patients in three MRC trials. [Abstract] Blood 104 (11): A-1794, 2004.

  • Burnett AK, Milligan D, Goldstone A, Prentice A, McMullin MF, Dennis M, Sellwood E, Pallis M, Russell N, Hills RK, Wheatley K; United Kingdom National Cancer Research Institute Haematological Oncology Study Group. The impact of dose escalation and resistance modulation in older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome: the results of the LRF AML14 trial. Br J Haematol. 2009 May;145(3):318-32. doi: 10.1111/j.1365-2141.2009.07604.x. Epub 2009 Mar 8.

    PubMed 19291085

  • Burnett AK, Milligan D, Prentice AG, Goldstone AH, McMullin MF, Hills RK, Wheatley K. A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment. Cancer. 2007 Mar 15;109(6):1114-24. doi: 10.1002/cncr.22496.

    PubMed 17315155

  • Burnett AK, Milligan DW, Prentice AG, et al.: Modification or dose or treatment duration has no impact on outcome of AML in older patients: preliminary results of the UK NCRI AML14 trial. [Abstract] Blood 106 (11): A-543, 2005.

  • Burnett AK, Milligan D, Prentice AG, et al.: Low dose Ara-C versus hydroxyurea with or without retinoid in older patients not considered fit for intensive chemotherapy: the UK NCRI AML14 trial. [Abstract] Blood 104 (11): A-872, 2004.

  • Pallis M, Truran L, Grundy M, et al.: P-Glycoprotein overexpresion and internal tandem duplications of FLT3 are characteristic of discrete populations of elderly AML patients. [Abstract] Blood 104 (11): A-196, 2004.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing cytarabine, daunorubicin hydrochloride and etoposide in people with Leukemia and Myelodysplastic Syndromes, run by Leukemia Research Fund at 3 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Survival. The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00005823, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2013.

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