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Adult Acute Myeloid Leukemia in RemissionPhase 2NCT00070135

Fludarabine and Busulfan Followed by Allogeneic Stem Cell Transplant in Treating Older Patients With Acute Myeloid Leukemia in First Complete Remission

A Phase 2 study testing filgrastim, Anti-Thymocyte Globulin and busulfan in people with Adult Acute Myeloid Leukemia in Remission and Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, run by Alliance for Clinical Trials in Oncology at 21 sites 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 fludarabine and busulfan followed by a donor (allogeneic) stem cell transplant work in treating older patients with acute myeloid leukemia that is in first complete remission. Read more about this study

Who is it for?
Ages 60 to 74 years
What is being tested?
filgrastim, Anti-Thymocyte Globulin and busulfan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
121 participants
Where
21 sitesUnited States
Study dates
Jan 2004to 15 Jun 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 to 74 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Eligibility Criteria:

  • Patients with acute myeloid leukemia (AML) (excluding French-American-British [FAB] classification system M3) who have achieved a first morphologic complete remission and who meet the criteria below; patients with preceding myelodysplastic syndrome (MDS) or treatment-related AML are eligible; patients with prior central nervous system (CNS) involvement are eligible as long as disease is in remission at transplant; patients with acute leukemia following blast transformation of prior chronic myeloid leukemia (CML) or other myeloproliferative disease are excluded
  • Complete remission (CR) will be defined according to the revised recommendations of the International Working Group (24) as all of the following:
  • Normal bone marrow morphology with < 5% blasts
  • Absolute neutrophil count (ANC) > 1,000/uL, referring to the count needed to confirm that the patient achieved a CR
  • Platelet count > 100,000/uL
  • No extramedullary leukemia
  • No blasts in peripheral blood
  • CR was achieved after one or two (but no more than two) cycles of induction chemotherapy with standard cytotoxic chemotherapy (e.g., cytarabine and an anthracycline) or after no more than four cycles of a hypomethylating agent containing regimen including either 5-azacytidine or decitabine
  • Patients may have received as many as but no more than two cycles of consolidation therapy prior to transplant; any consolidation regimen that does not require transplant can be used; no more than 6 months can elapse from documentation of morphologic CR to transplant; the platelet count does not need to be > 100,000/uL after consolidation, as long as the bone marrow assessment prior to transplant does not show relapse
  • Identification of hematopoietic cell donor
  • >= 4 weeks since prior chemotherapy, radiation therapy, and surgery
  • Performance status 0-2
  • Diffusion capacity of carbon monoxide (DLCO) > 40% with no symptomatic pulmonary disease
  • Left ventricular ejection fraction (LVEF) by multi gated acquisition scan (MUGA) or echocardiogram (ECHO) >= 30%
  • No uncontrolled diabetes mellitus or active serious infection requiring antibiotics
  • No known hypersensitivity to E. coli-derived products
  • No human immunodeficiency virus (HIV) infection
  • Calculated creatinine clearance >= 40 cc/min
  • Bilirubin < 2 mg/dL
  • If bilirubin is 2-3 mg/dL, but direct bilirubin is normal then patient will be considered eligible
  • Aspartate aminotransferase (AST) < 3 x upper limit of normal
  • DONOR: HLA-identical sibling (6/6); the donor must be determined to be an human leukocyte antigen (HLA)-identical sibling (6/6) by serologic typing for class (A, B) and low resolution molecular typing for class II (DRB1)
  • DONOR: Matched unrelated donor (10/10); high resolution molecular typing at the following loci is required: HLA-A, -B, -C, -DRB1, and -DQB1
  • DONOR: the donor must be healthy and must be an acceptable donor as per institutional standards for stem cell donation
  • DONOR: the donor must have no significant cardiopulmonary, renal, endocrine, or hepatic disease
  • DONOR: there is no donor age restriction if the donor is a matched sibling
  • DONOR: syngeneic donors are not eligible

Trial locations and contacts

21 sites in 1 country.

21 sites in 1 country

United States21 sites

  • Greenebaum Cancer Center at University of Maryland Medical Center

    Baltimore, Maryland, 21201

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana-Farber/Brigham and Women's Cancer Center

    Boston, Massachusetts, 02115

  • Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263-0001

  • Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210-1240

  • Union Hospital of Cecil County

    Elkton, Maryland, 21921

  • Monter Cancer Center of the North Shore-LIJ Health System

    Lake Success, New York, 11042

  • Tunnell Cancer Center at Beebe Medical Center

    Lewes, Delaware, 19958

  • CCOP - North Shore University Hospital

    Manhasset, New York, 11030

  • Don Monti Comprehensive Cancer Center at North Shore University Hospital

    Manhasset, New York, 11030

  • Masonic Cancer Center at University of Minnesota

    Minneapolis, Minnesota, 55455

  • Long Island Jewish Medical Center

    New Hyde Park, New York, 11040

  • New York Weill Cornell Cancer Center at Cornell University

    New York, New York, 10021

  • Mount Sinai Medical Center

    New York, New York, 10029

  • CCOP - Christiana Care Health Services

    Newark, Delaware, 19713

  • UCSF Helen Diller Family Comprehensive Cancer Center

    San Francisco, California, 94115

  • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

    St Louis, Missouri, 63110

  • Cancer Institute of New Jersey at Cooper - Voorhees

    Voorhees Township, New Jersey, 08043

  • Wake Forest University Comprehensive Cancer Center

    Winston-Salem, North Carolina, 27157-1096

Other trials in United States

About this study

Official title: A Phase II Study Of Allogeneic Transplant For Older Patients With AML In First Morphologic Complete Remission Using A Non-Myeloablative Preparative Regimen

This phase II trial studies how well fludarabine and busulfan followed by a donor (allogeneic) stem cell transplant work in treating older patients with acute myeloid leukemia that is in first complete remission. Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stops the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Giving tacrolimus, methotrexate, and rabbit antithymocyte globulin before or after the transplant may stop this from happening.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine if allogeneic transplantation from a matched sibling or unrelated donor using a non-myeloablative preparative regimen results in a 2-year disease-free survival (DFS) that is better than historical results using standard chemotherapy.

SECONDARY OBJECTIVES:

  1. Determine 2-year actuarial risks of transplant-related mortality, acute and chronic graft-versus-host (GVHD) disease and relapse among patients with acute myeloid leukemia (AML) in first complete remission (CR1) following a non-myeloablative preparative regimen.

II. To examine recovery of T and B cell number and function following non-myeloablative stem cell transplant.

III. To examine the time course of T, B and myeloid progenitor chimerism following this preparative regimen.

IV. To characterize the pharmacokinetics of intravenous busulfan used in a non-myeloablative preparation regimen in AML patients age >= 60 years.

OUTLINE:

PREPARATIVE REGIMEN: Patients receive fludarabine intravenously (IV) over 30 minutes on days -7 to -3 and busulfan IV over 2 hours 4 times per day (every 6 hours) on days -4 and -3.

GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive tacrolimus orally (PO) or IV twice daily (BID) on days -2 with taper between days 90-120, and stopping by days 150-180. Patients also receive methotrexate IV on days 1, 3, 6, and 11 and rabbit antithymocyte globulin IV over 4-6 hours on days -4 through -2.

ALLOGENEIC PERIPHERAL BLOOD STEM CELL TRASNPLANTATION (PBSC): Patients undergo allogeneic PBSC transplant on day 0. Patients then receive filgrastim subcutaneously (SC) daily beginning on day 12 and continuing until blood counts recover.

Patients are followed monthly for 1 year, every 3 months for 1 year, and then every 6 months for 3 years.

Being tested
filgrastim, Anti-Thymocyte Globulin, busulfan, fludarabine phosphate, methotrexate
Keywords
adult acute myeloid leukemia in remission, secondary acute myeloid leukemia, adult acute monocytic leukemia (M5b), adult acute erythroid leukemia (M6), adult acute megakaryoblastic leukemia (M7), adult acute minimally differentiated myeloid leukemia (M0), adult acute myeloblastic leukemia with maturation (M2), adult acute myeloblastic leukemia without maturation (M1), adult acute myelomonocytic leukemia (M4), adult acute monoblastic leukemia (M5a), adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with 11q23 (MLL) abnormalities
Medical subject headings
Leukemia, Monocytic, Acute, Leukemia, Erythroblastic, Acute, Leukemia, Megakaryoblastic, Acute, Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Acute, Congenital Abnormalities

What participants receive

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

Study groups in NCT00070135
Study groupRoleWhat they receive
Treatment (fludarabine, busulfan, allogeneic PBSC)ExperimentalPREPARATIVE REGIMEN: Patients receive fludarabine IV over 30 minutes on days -7 to -3 and busulfan IV over 2 hours 4 times per day (every 6 hours) on days -4 and -3. GVHD PROPHYLAXIS: Patients receive tacrolimus PO or IV BID on days -2 with taper between days 90-120, and stopping by days 150-180. Patients also receive methotrexate IV on days 1, 3, 6, and 11 and rabbit antithymocyte globulin IV over 4-6 hours on days -4 through -2. ALLOGENEIC PBSC: Patients undergo allogeneic PBSC transplant on day 0. Patients then receive filgrastim SC daily beginning on day 12 and continuing until blood counts recover.
Receives: Biological: filgrastim; Biological: Anti-Thymocyte Globulin; Drug: busulfan; Drug: fludarabine phosphate; Drug: methotrexate; Drug: tacrolimus; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation

What is being measured

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

  1. 2 Year Disease Free Survival In Unrelated Donor Recipient Group

    Percentage of participants who were alive and relapse free at 2 years for patients who were matched with an unrelated donor for transplant. The 2 year disease free survival, with 95% confidence interval, was estimated using the Kaplan Meier method.

    A relapse is defined as any of the following:

    • Reappearance of leukemia blasts cells in peripheral blood
    • >5% blasts in the marrow, not attributable to another cause (e.g., bone marrow regeneration)
    • If there are no circulating blasts, but the marrow contains 5-20% blasts, a repeat bone marrow ≥ 1 week later with >5% blasts is necessary to meet the criteria for relapse
    • The development of extramedullary leukemia or leukemic cells in the cerebral spinal fluid

    Measured: 2 years

Secondary outcomes (2)

  1. 2 Year DFS for All Patients

    Percentage of participants who were alive and relapse free at 2 years for all patients. The 2 year disease free survival, with 95% confidence interval, was estimated using the Kaplan Meier method.

    Measured: Up to 2 years

  2. Non-relapse Mortality (NRM)

    Percentage of patients who died due to causes other than relapse

    Measured: Up to 5 years

Timeline

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

  1. First posted7 Oct 2003 (estimated)
  2. Study startJan 2004
  3. Primary completionDec 2013
  4. Study completion15 Jun 2016

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
121 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00070135
Sponsor's protocol ID
CALGB-100103
Other IDs
CDR0000330001, NCI-2009-00438, U10CA180821
Status last verified
May 2018
First submitted
3 Oct 2003
Last updated
12 Jun 2018
Data monitoring committee
Yes

Publications

  • Devine SM, Owzar K, Blum W, Mulkey F, Stone RM, Hsu JW, Champlin RE, Chen YB, Vij R, Slack J, Soiffer RJ, Larson RA, Shea TC, Hars V, Sibley AB, Giralt S, Carter S, Horowitz MM, Linker C, Alyea EP. Phase II Study of Allogeneic Transplantation for Older Patients With Acute Myeloid Leukemia in First Complete Remission Using a Reduced-Intensity Conditioning Regimen: Results From Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502. J Clin Oncol. 2015 Dec 10;33(35):4167-75. doi: 10.1200/JCO.2015.62.7273. Epub 2015 Nov 2.

    PubMed 26527780

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing filgrastim, Anti-Thymocyte Globulin and busulfan in people with Adult Acute Myeloid Leukemia in Remission and Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, run by Alliance for Clinical Trials in Oncology at 21 sites in United States.

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 12 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

2 Year Disease Free Survival In Unrelated Donor Recipient Group (time frame: 2 years). 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 NCT00070135, which also lists 1 linked publication.

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 12 Jun 2018.

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