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Acute Undifferentiated LeukemiaPhase 1/2NCT00006251

Fludarabine Phosphate, Low-Dose Total-Body Irradiation, and Donor Stem Cell Transplant Followed by Cyclosporine, Mycophenolate Mofetil, Donor Lymphocyte Infusion in Treating Patients With Hematopoietic Cancer

A Phase 1/2 study testing total-body irradiation, fludarabine phosphate and cyclosporine in people with Acute Undifferentiated Leukemia and Adult Nasal Type Extranodal NK/T-cell Lymphoma, run by Fred Hutchinson Cancer Center at 2 sites in 2 countries.

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 clinical trial studies fludarabine phosphate, low-dose total-body irradiation, and donor stem cell transplant followed by cyclosporine, mycophenolate mofetil, and donor lymphocyte infusion in treating patients with hematopoietic cancer. Read more about this study

Who is it for?
Ages Up to 74 years
What is being tested?
total-body irradiation, fludarabine phosphate and cyclosporine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
2 sitesin 2 countries
Study dates
May 2000to Sep 2005
Phase
Phase 1/2
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 74 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Patients aged > 49 years and < 75 years with non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma who are not eligible for a curative autologous transplantation or who have failed prior autologous transplantation; patients with NHL and CLL must have failed prior therapy with an alkylating agent and/or fludarabine, or be at high risk of relapse; patients with multiple myeloma must have stage II or III disease and received prior chemotherapy
  • Patients < 50 years of age with NHL, CLL or multiple myeloma at high risk of regimen related toxicity through prior autologous transplant or through pre-existing medical conditions
  • Patients < 75 years of age with other malignant diseases treatable by allogeneic bone marrow transplant (BMT) whom through pre-existing chronic disease affecting kidneys, liver, lungs, and heart are considered to be at high risk for regimen related toxicity using standard high dose regimens; the following diseases are the likely candidates:
  • Myelodysplastic syndromes
  • Myeloproliferative syndromes
  • Acute Leukemia with < 10% blasts
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  • Amyloidosis
  • Hodgkin's disease
  • Renal cell carcinoma
  • Patients with other malignancies declining standard allografts may be approved for transplant following presentation and approval by the Fred Hutchinson Cancer Research Center (FHCRC) chimerism group
  • DONOR:
  • Human leukocyte antigen (HLA) genotypically or phenotypically identical related donor
  • Donor must consent to granulocyte colony-stimulating factor (G-CSF) administration and leukopheresis
  • Donor must have adequate veins for leukopheresis or agree to placement of central venous catheter (femoral, subclavian)
  • Age < 75 years

Who cannot join

  • Eligible for a high-priority curative autologous transplant
  • Patients with rapidly progressive aggressive NHL unless in minimal disease state
  • Active central nervous system (CNS) involvement with disease
  • Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
  • Females who are pregnant
  • Patients who are human immunodeficiency virus (HIV) positive
Show all 21Show fewer
  • Cardiac ejection fraction < 40%
  • Severe defects in pulmonary function testing (defects are currently categorized as mild, moderate and severe) as defined by the pulmonary consultant, or receiving supplementary continuous oxygen
  • Total bilirubin > 2 x the upper limit of normal
  • Serum glutamate pyruvate transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) 4 x the upper limit of normal
  • Karnofsky score < 50
  • Patients with poorly controlled hypertension
  • Patients with renal failure are eligible, however patients with renal compromise (serum creatinine greater than 2.0) will likely have further compromise in renal function and may require hemodialysis (which may be permanent) due to the need to maintain adequate serum cyclosporine levels
  • DONOR:
  • Identical twin
  • Age less than 12 years
  • Pregnancy
  • Infection with HIV
  • Inability to achieve adequate venous access
  • Known allergy to G-CSF
  • Current serious systemic illness

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

United States1 site

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

    Seattle, Washington, 98109

Other trials in United States

Italy1 site

  • University of Torino

    Torino, 10126

Other trials in Italy

About this study

Official title: Induction of Mixed Hematopoietic Chimerism in Patients Using Fludarabine, Low Dose TBI, PBSC Infusion and Post-Transplant Immunosuppression With Cyclosporine and Mycophenolate Mofetil

This clinical trial studies fludarabine phosphate, low-dose total-body irradiation, and donor stem cell transplant followed by cyclosporine, mycophenolate mofetil, and donor lymphocyte infusion in treating patients with hematopoietic cancer. Giving low doses of chemotherapy, such as fludarabine phosphate, and total body irradiation (TBI) before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also keep the patient's immune response from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To estimate the risk of graft rejection associated with the addition of fludarabine (fludarabine phosphate) to a non-myeloablative conditioning regimen for patients with malignant diseases treatable by allogeneic stem cell transplantation and compare this rate to that observed among patients previously treated without fludarabine.

II. To estimate the rate of grade acute II/IV graft-vs-host disease (GVHD) and chronic GVHD in patients treated with low-dose total-body irradiation (TBI), fludarabine, peripheral blood stem cell (PBSC) infusion and immunosuppression with cyclosporine and mycophenolate mofetil.

OUTLINE:

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days - 4 to -2 and undergo low-dose TBI on day 0. (Note: Patients who have had an autologous transplant within 90 days prior to day 0 will not receive fludarabine phosphate.)

PBSC INFUSION: Patients undergo allogeneic PBSC transplant on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) twice daily (BID) on days -3 to 35 with a taper to day 56. Patients receive mycophenolate mofetil PO BID on days 0-27.

POST TRANSPLANT DONOR LYMPHOCYTE INFUSION (DLI): Patients with stable mixed chimerism on day 56, and without evidence of GVHD, undergo DLI IV over 30 minutes on day 65. Patients without a complete response, full donor chimerism, and GVHD after 2 months undergo further DLI at higher cell numbers. Up to 6 DLIs may be given 65 days apart.

After completion of study treatment, patients are followed up at 4, 6, 12, 18 and 24 months and then annually thereafter.

Being tested
total-body irradiation, fludarabine phosphate, cyclosporine, mycophenolate mofetil, nonmyeloablative allogeneic hematopoietic stem cell transplantation
Medical subject headings
Leukemia, Biphenotypic, Acute, Lymphoma, Extranodal NK-T-Cell, Lymphoma, Large-Cell, Anaplastic, Immunoblastic Lymphadenopathy, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Leukemia, Myelomonocytic, Chronic, Intraocular Lymphoma

What participants receive

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

  • total-body irradiationRadiation

    Also called TBI

    Undergo TBI

  • fludarabine phosphateDrug

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

    Given IV

  • cyclosporineDrug

    Also called ciclosporin, cyclosporin, cyclosporin A, CYSP

    Given PO

  • mycophenolate mofetilDrug

    Also called Cellcept, MMF

    Given PO

  • nonmyeloablative allogeneic hematopoietic stem cell transplantationProcedure or surgery

    Undergo allogeneic PBSC transplant

  • donor lymphocytesBiological

    Undergo DLI

  • peripheral blood stem cell transplantationProcedure or surgery

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

    Undergo allogeneic PBSC transplant

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00006251
Study groupRoleWhat they receive
Treatment (fludarabine phosphate, TBI, PBSC transplant, DLI)ExperimentalCONDITIONING REGIMEN : Patients receive fludarabine phosphate IV on days - 4 to -2 and undergo low-dose TBI on day 0. (Note: Patients who have had an autologous transplant within 90 days prior to day 0 will not receive fludarabine phosphate.) PBSC INFUSION: Patients undergo allogeneic PBSC transplant on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID on days -3 to 35 with a taper to day 56. Patients receive mycophenolate mofetil PO BID on days 0-27. POST TRANSPLANT DLI: Patients with stable mixed chimerism on day 56, and without evidence of GVHD, undergo DLI IV over 30 minutes on day 65. Patients without a complete response, full donor chimerism, and GVHD after 2 months undergo further DLI at higher cell numbers. Up to 6 DLIs may be given 65 days apart.
Receives: Radiation: total-body irradiation; Drug: fludarabine phosphate; Drug: cyclosporine; Drug: mycophenolate mofetil; Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation; Biological: donor lymphocytes; Procedure: peripheral blood stem cell transplantation; Other: laboratory biomarker analysis

What is being measured

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

  1. Risk of graft rejection defined as the absence of detectable peripheral blood donor T cells with the addition of fludarabine phosphate

    Measured: Up to day 56

  2. Incidence of acute grade II/IV GVHD

    Measured: Up to day 90 after the last DLI

  3. Incidence of chronic GVHD

    Measured: Up to 24 months

Secondary outcomes (5)

  1. Incidence of myelosuppression (ANC < 500/ul for > 2 days, platelets < 20,000/ul for > 2 days) after initial PBSC infusion

    Measured: Up to day 56

  2. Response of malignancy to DLI

    Measured: Up to 24 months

  3. Incidence of aplasia after DLI

    Measured: Up to 24 months

  4. Dose of CD3+ cells required to convert mixed to full lymphoid chimeras

    Measured: Up to 24 months

  5. Incidence of non-relapse mortality

    Measured: Up to 24 months

Timeline

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

  1. First posted9 Jun 2004 (estimated)
  2. Study startMay 2000
  3. Primary completionSep 2005

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00006251
Sponsor's protocol ID
1533.00
Other IDs
NCI-2013-01634, 1533.00, P01CA078902, P30CA015704
Status last verified
Jan 2020
First submitted
11 Sep 2000
Last updated
21 Jan 2020
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 1/2 study testing total-body irradiation, fludarabine phosphate and cyclosporine in people with Acute Undifferentiated Leukemia and Adult Nasal Type Extranodal NK/T-cell Lymphoma, run by Fred Hutchinson Cancer Center at 2 sites in 2 countries.

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 15 inclusion and 21 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 21 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States, Italy. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Risk of graft rejection defined as the absence of detectable peripheral blood donor T cells with the addition of fludarabine phosphate (time frame: Up to day 56). 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 NCT00006251, 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 21 Jan 2020; AzTrials last refreshed its copy on 26 Oct 2026.

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