NCT00031655

Brief Summary

The reason for doing this study is to determine whether a new method of blood stem cell transplant (also known as bone marrow transplant) is able to treat acute lymphocytic leukemia. Blood stem cells are the "seed cells" necessary to make all blood cells. This new method of transplant uses a combination of low dose radiation and chemotherapy that may be less toxic and cause less harm than a conventional transplant. This lower dose transplant is called a "nonmyeloablative transplant". Researchers want to see if using less radiation and less chemotherapy combined with new immune suppressing drugs after the transplant will help a stem cell transplant to work. Researchers hope that this treatment will cure acute lymphocytic leukemia with fewer side effects. Researchers are hoping to see a mixture of recipient and donor blood cells after transplant. This mixture of donor and recipient blood cells is called "mixed chimerism". Researchers hope that donor cells will attack and eliminate the leukemia. This is called the "graft-versus-leukemia" effect. In addition, after the transplant, white blood cells from the donor may be given to enhance or "boost" the graft-versus-leukemia effect, and hopefully remove all remaining cancer cells. This study is being done because at the present time blood stem cell transplantation (or bone marrow transplantation) is the only known curative therapy for acute lymphocytic leukemia. Because of age or underlying health status acute lymphocytic leukemia patients have a higher likelihood of experiencing severe harm from a conventional blood stem cell transplant. Researchers are doing this study to see if this new nonmyeloablative method of low dose radiation and low dose chemotherapy given before transplant and immune suppressive drugs after transplant will help make the transplant safer and also cure acute lymphocytic leukemia

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Sep 2001

Longer than P75 for phase_2

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2001

Completed
6 months until next milestone

First Submitted

Initial submission to the registry

March 8, 2002

Completed
11 months until next milestone

First Posted

Study publicly available on registry

January 27, 2003

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2006

Completed
6.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2012

Completed
Last Updated

December 7, 2012

Status Verified

December 1, 2012

Enrollment Period

4.9 years

First QC Date

March 8, 2002

Last Update Submit

December 5, 2012

Conditions

Adult Acute Lymphoblastic Leukemia in RemissionChildhood Acute Lymphoblastic Leukemia in RemissionRecurrent Adult Acute Lymphoblastic LeukemiaRecurrent Childhood Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (1)

  • Leukemia-free survival

    Incidence of survival without relapse. Kaplan-Meier estimates will be used to estimate one-year leukemia-free survival.

    1 year

Secondary Outcomes (9)

  • Transplant-related mortality

    Day +200

  • Transplant-related mortality

    1 year

  • Efficacy of DLI for the elimination of MRD

    Up to day 120

  • Toxicity of DLT, graded using a modified version of the National Cancer Institute (NCI) Common Toxicity Criteria

    Up to 5 years

  • Overall survival

    1 year

  • +4 more secondary outcomes

Study Arms (1)

Treatment (nonmyeloablative allogeneic PBSCT)

EXPERIMENTAL

NONMYELOALATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0. Patients with minimal residual disease may receive donor lymphocyte infusion IV. IMMUNOSUPPRESSION: Patients receive cyclosporine PO every 12 hours on days -3 to 100 with taper to day 177 and mycophenolate mofetil PO very 8 hours on days 0 to 40 with taper to day 96.

Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantationBiological: donor lymphocytesDrug: cyclosporineRadiation: total-body irradiationDrug: fludarabine phosphateDrug: mycophenolate mofetilOther: laboratory biomarker analysisProcedure: peripheral blood stem cell transplantation

Interventions

nonmyeloablative allogeneic hematopoietic stem cell transplantationPROCEDURE

Undergo nonmyeloablative allogeneic PBSCT

Treatment (nonmyeloablative allogeneic PBSCT)
donor lymphocytesBIOLOGICAL

Given IV

Treatment (nonmyeloablative allogeneic PBSCT)
cyclosporineDRUG

Given PO

Also known as: ciclosporin, cyclosporin, cyclosporin A, CYSP, Sandimmune
Treatment (nonmyeloablative allogeneic PBSCT)
total-body irradiationRADIATION

Undergo TBI

Also known as: TBI
Treatment (nonmyeloablative allogeneic PBSCT)
fludarabine phosphateDRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, Fludara
Treatment (nonmyeloablative allogeneic PBSCT)
mycophenolate mofetilDRUG

Given PO

Also known as: Cellcept, MMF
Treatment (nonmyeloablative allogeneic PBSCT)
laboratory biomarker analysisOTHER

Correlative studies

Treatment (nonmyeloablative allogeneic PBSCT)
peripheral blood stem cell transplantationPROCEDURE

Undergo nonmyeloablative allogeneic PBSCT

Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell
Treatment (nonmyeloablative allogeneic PBSCT)

Eligibility Criteria

AgeUp to 75 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • ADULT PATIENTS:
  • Patients 50-75 years old with high risk ALL in first CR (CR1) or ALL in CR \>= second CR (CR2)
  • Patients \>= 18 years old and \< 50 years old with high risk ALL in CR1 who are not eligible for a conventional allogeneic transplantation based on general medical condition
  • Patients \>= 18 years old and \< 50 years old with high risk ALL in CR1 who refuse a conventional allogeneic transplant
  • Patients \>= 18 years old and \< 50 years old with ALL in CR \>= CR2 who are not eligible for a conventional allogeneic transplantation based on general medical condition
  • Patients \>= 18 years old and \< 50 years old with high risk ALL in CR \>= CR2 who refuse a conventional allogeneic transplant
  • CR is defined as \< 5% blasts by morphology on a bone marrow aspirate and the absence of peripheral blasts
  • High risk adult ALL in CR1 includes those patients with one or more of the following:
  • Age \>=30 years
  • Non T-cell phenotype
  • Cytogenetic abnormalities including t(9;22), t(4;11), trisomy 8, or monosomy 7
  • Failure to achieve CR after 4 weeks of induction chemotherapy
  • PEDIATRIC PATIENTS:
  • Patients \< 18 years old with ALL in high risk CR1 who are not candidates for conventional allogeneic transplantation based on general medical condition
  • Patients \< 18 years old with ALL in CR \>= CR2 who are not candidates for conventional allogeneic transplantation based on general medical condition
  • +14 more criteria

You may not qualify if:

  • Active central nervous system (CNS) disease
  • Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology
  • Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
  • Pregnancy or breastfeeding
  • Human immunodeficiency virus (HIV) seropositivity
  • ORGAN DYSFUNCTION, ADULT CRITERIA:
  • Requiring supplementary continuous oxygen OR diffusing capacity of the lung for carbon monoxide (DLCO) \< 40%
  • Cardiac ejection fraction \< 35%
  • Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bridging fibrosis, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin \> 3 mg/dL, and symptomatic biliary disease
  • Karnofsky performance score \< 50
  • ORGAN DYSFUNCTION, PEDIATRIC CRITERIA:
  • Lansky play-performance score \< 40
  • Patients with active non-hematologic malignancies (except non-melanoma skin cancers)
  • Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a \> 20% risk of disease recurrence

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Oregon Health and Sciences University

Portland, Oregon, United States

Location

Veterans Affairs Puget Sound Healthcare System

Seattle, Washington, 98108, United States

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

  • Cooper JP, Storer BE, Granot N, Gyurkocza B, Sorror ML, Chauncey TR, Shizuru J, Franke GN, Maris MB, Boyer M, Bruno B, Sahebi F, Langston AA, Hari P, Agura ED, Lykke Petersen S, Maziarz RT, Bethge W, Asch J, Gutman JA, Olesen G, Yeager AM, Hubel K, Hogan WJ, Maloney DG, Mielcarek M, Martin PJ, Flowers MED, Georges GE, Woolfrey AE, Deeg JH, Scott BL, McDonald GB, Storb R, Sandmaier BM. Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies: Improved outcomes over two decades. Haematologica. 2021 Jun 1;106(6):1599-1607. doi: 10.3324/haematol.2020.248187.

    PMID: 32499241DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

CyclosporineWhole-Body Irradiationfludarabine phosphateMycophenolic AcidPeripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Leukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

CyclosporinsPeptides, CyclicMacrocyclic CompoundsPolycyclic CompoundsPeptidesAmino Acids, Peptides, and ProteinsRadiotherapyTherapeuticsInvestigative TechniquesCaproatesAcids, AcyclicCarboxylic AcidsOrganic ChemicalsFatty AcidsLipidsHematopoietic Stem Cell TransplantationStem Cell TransplantationCell TransplantationCell- and Tissue-Based TherapyBiological TherapyTransplantationSurgical Procedures, Operative

Study Officials

  • George Georges

    Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER

Study Record Dates

First Submitted

March 8, 2002

First Posted

January 27, 2003

Study Start

September 1, 2001

Primary Completion

August 1, 2006

Study Completion

November 1, 2012

Last Updated

December 7, 2012

Record last verified: 2012-12

Locations

US(3)