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Adult Acute Lymphoblastic Leukemia in RemissionPhase 2NCT00031655

Reduced Intensity Donor Stem Cell Transplant in Treating Patients With High Risk Acute Lymphocytic Leukemia in Complete Remission

A Phase 2 study testing nonmyeloablative allogeneic hematopoietic stem cell transplantation, donor lymphocytes and cyclosporine in people with Adult Acute Lymphoblastic Leukemia in Remission and Childhood Acute Lymphoblastic Leukemia in Remission, run by Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium at 3 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

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. Read more about this study

Who is it for?
Ages Up to 75 years
What is being tested?
nonmyeloablative allogeneic hematopoietic stem cell transplantation, donor lymphocytes and cyclosporine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
3 sitesUnited States
Study dates
Sep 2001to Nov 2012
Phase
Phase 2
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 Up to 75 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Patients < 12 years old require approval by the Fred Hutchinson Cancer Research Center (FHCRC) principal investigator prior to enrollment
  • CR is defined as < 5% blasts by morphology on a bone marrow aspirate and absence of peripheral blasts
  • High risk pediatric ALL in CR1 includes those patients with one or more of the following:
  • Cytogenetic abnormalities including:
  • t(9;22) with a white blood cell (WBC) >= 25,000 at diagnosis or
  • t(4;11) in patients < 1 year old and >= 10 years old or
  • Hypodiploidy (< 45 chromosomes)
  • Failure to achieve CR after 4 weeks of induction chemotherapy
  • Persistent peripheral blasts after one week of induction chemotherapy
  • DONOR: FHCRC matching Grade 2.1: Unrelated donors who are prospectively:
  • Matched for human leukocyte antigen (HLA)-DRB1 and DQB1 alleles (must be defined by high resolution typing) and
  • Only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing
  • DONOR: A positive anti-donor cytotoxic crossmatch is an absolute donor exclusion; donors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment; this determination is based on the standard practice of the individual institution; the recommended procedure for patients with 10 of 10 HLA allele level (phenotypic) match is to obtain a panel reactive antibody (PRA) screens to class I and class II antigens for all patients before hematopoietic cell transplantation (HCT); if the PRA shows > 10% activity, then flow cytometric or B and T cell cytotoxic cross matches should be obtained; the donor should be excluded if any of the cytotoxic cross match assays are positive; for those patients with an HLA class I allele mismatch, flow cytometric or B and T cell cytotoxic cross matches should be obtained regardless of the PRA results
  • DONOR: Patient and donor pairs homozygous at a mismatched allele are considered a two-allele mismatch, i.e., the patient is A*0101 and the donor is A*0102, and this type of mismatch is not allowed
  • DONOR: Donor must consent to peripheral blood stem cell (PBSC) mobilization with filgrastim (G-CSF) arranged through the National Marrow Donor Program (NMDP) or other donor centers

Who cannot join

  • 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:
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  • 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

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Oregon Health and Sciences University

    Portland, Oregon

  • Veterans Affairs Puget Sound Healthcare System

    Seattle, Washington, 98108

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation From HLA Matched Unrelated Donors for Treatment of Patients With High Risk Acute Lymphocytic Leukemia in Complete Remission - A Multicenter Trial

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

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine if a one-year disease-free survival (DFS) of > 25% can be achieved among adult patients with high risk acute lymphocytic leukemia (ALL) in complete remission (CR) who undergo nonmyeloablative allografting.

II. To determine if a one-year DFS of >= 40% can be achieved among pediatric patients with high risk ALL in CR who undergo nonmyeloablative allografting.

SECONDARY OBJECTIVES:

  1. To determine if a day +200 transplant-related mortality (TRM) of < 25% can be achieved among patients with high risk ALL in CR who undergo nonmyeloablative allografting.

II. To evaluate the efficacy and toxicity of donor lymphocyte infusion (DLI) in the treatment of minimal residue disease (MRD) after nonmyeloablative allografting for patients with high risk ALL in CR.

OUTLINE:

NONMYELOALATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2 and undergo total body irradiation (TBI) on day 0.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation (PBSCT) on day 0. Patients with minimal residual disease may receive donor lymphocyte infusion IV.

IMMUNOSUPPRESSION: Patients receive cyclosporine orally (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.

After completion of study treatment, patients are followed up at days 28, 56, 84, 120, 180, and 360; at 18 months; and annually for up to 5 years.

Being tested
nonmyeloablative allogeneic hematopoietic stem cell transplantation, donor lymphocytes, cyclosporine, total-body irradiation, fludarabine phosphate
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

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

  • nonmyeloablative allogeneic hematopoietic stem cell transplantationProcedure or surgery

    Undergo nonmyeloablative allogeneic PBSCT

  • donor lymphocytesBiological

    Given IV

  • cyclosporineDrug

    Also called ciclosporin, cyclosporin, cyclosporin A, CYSP

    Given PO

  • total-body irradiationRadiation

    Also called TBI

    Undergo TBI

  • fludarabine phosphateDrug

    Also called 2-F-ara-AMP, Beneflur, Fludara

    Given IV

  • mycophenolate mofetilDrug

    Also called Cellcept, MMF

    Given PO

  • laboratory biomarker analysisOther

    Correlative studies

  • peripheral blood stem cell transplantationProcedure or surgery

    Also called PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

    Undergo nonmyeloablative allogeneic PBSCT

Study groups in NCT00031655
Study groupRoleWhat they receive
Treatment (nonmyeloablative allogeneic PBSCT)ExperimentalNONMYELOALATIVE 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.
Receives: Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation; Biological: donor lymphocytes; Drug: cyclosporine; Radiation: total-body irradiation; Drug: fludarabine phosphate; Drug: mycophenolate mofetil; Other: laboratory biomarker analysis; Procedure: peripheral blood stem cell transplantation

What is being measured

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

  1. Leukemia-free survival

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

    Measured: 1 year

Secondary outcomes (9)

  1. Transplant-related mortality

    Measured: Day +200

  2. Transplant-related mortality

    Measured: 1 year

  3. Efficacy of DLI for the elimination of MRD

    Measured: Up to day 120

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

    Measured: Up to 5 years

  5. Overall survival

    Measured: 1 year

  6. Incidence of relapse

    Measured: 1 year

  7. Incidence of rejection

    Measured: 1 year

  8. Incidence of acute grade II-IV graft-versus-host disease (GVHD) and chronic GVHD, graded using a modified version of the National Cancer Institute (NCI) Common Toxicity Criteria

    Measured: Up to 5 years

  9. Karnofsky performance score and Lansky performance score

    Measured: 1 year

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 startSep 2001
  3. Primary completionAug 2006
  4. Study completionNov 2012

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
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00031655
Sponsor's protocol ID
1623.00
Other IDs
NCI-2012-00580, P01CA018029
Status last verified
Dec 2012
First submitted
8 Mar 2002
Last updated
7 Dec 2012
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 32499241

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing nonmyeloablative allogeneic hematopoietic stem cell transplantation, donor lymphocytes and cyclosporine in people with Adult Acute Lymphoblastic Leukemia in Remission and Childhood Acute Lymphoblastic Leukemia in Remission, run by Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium at 3 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?

The sponsor lists 30 inclusion and 14 exclusion criteria. 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 7 Dec 2012. 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 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?

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?

Leukemia-free survival (time frame: 1 year). 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 NCT00031655, 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 7 Dec 2012.

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