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B-Cell Prolymphocytic LeukemiaPhase 2NCT00060424

Fludarabine Phosphate and Total-Body Irradiation Before Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia

A Phase 2 study testing Cyclosporine, Fludarabine Phosphate and Hematopoietic Cell Transplantation in people with B-Cell Prolymphocytic Leukemia and Chronic Lymphocytic Leukemia, run by Fred Hutchinson Cancer Center at 3 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 how well giving fludarabine phosphate together with total-body irradiation (TBI) before donor peripheral blood stem cell transplant works in treating patients with chronic lymphocytic leukemia or small lymphocytic leukemia. Read more about this study

Who is it for?
Ages 21 years and older
What is being tested?
Cyclosporine, Fludarabine Phosphate and Hematopoietic Cell Transplantation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
3 sitesin 2 countries
Study dates
Mar 2003to 22 Sep 2010
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 21 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with CLL (or small lymphocytic lymphoma) or diagnosis of CLL that progresses to prolymphocytic leukemia (PLL), or T-cell CLL or PLL
  • Patients with B-Cell CLL or PLL who have at least one of the following:
  • Failed to meet National Cancer Institute (NCI) Working Group criteria for complete or partial response after therapy with a regimen containing fludarabine (or another nucleoside analog, e.g. cladribine [2-CDA], pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing fludarabine (or another nucleoside analog)
  • Failed FCR combination chemotherapy at any time point
  • Had de novo of acquired "17p deletion" cytogenetic abnormality; patients should have received induction chemotherapy but could be transplanted in first (1st) complete response (CR)
  • Patient has a suitable human leukocyte antigen (HLA)-matched related donor who is willing to undergo leukapheresis initially for collection of PBSC and subsequently for collection of peripheral blood mononuclear cells (PBMC) with filgrastim (G-CSF) mobilization and willing to donate stem cells
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  • DONOR: Related donor who is HLA phenotypically or genotypically identical at the allele level at HLA-A, -B, -C, -DRB1, and -DQB1
  • DONOR: Donor must consent to G-CSF administration and leukapheresis
  • DONOR: Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian)

Who cannot join

  • Infection with human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV)-1, or HTLV-2
  • Active central nervous system (CNS) involvement with CLL
  • 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
  • Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
  • Pregnant or breastfeeding women
Show all 20Show fewer
  • Karnofsky score =< 70
  • Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month
  • Cytotoxic agents for "cytoreduction" (with the exception of imatinib mesylate [Gleevec], cytokine therapy, hydroxyurea, chlorambucil or Rituxan) within three weeks of the initiation of conditioning
  • Active bacterial or fungal infections unresponsive to medical therapy
  • Cardiovascular: cardiac ejection fraction < 40%; patients with poorly controlled hypertension despite multiple antihypertensives
  • Pulmonary: diffusing capacity of carbon monoxide (DLCO) < 40%, total lung capacity (TLC) < 40%, forced expiratory volume in one second (FEV1) < 40% and/or requiring continuous supplementary oxygen, or severe deficits in pulmonary function testing as defined by pulmonary consultant service
  • Liver function abnormalities: 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, bridging fibrosis, 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, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3mg/dL, or symptomatic biliary disease
  • DONOR: Age < 12 years
  • DONOR: Identical twin
  • DONOR: Pregnancy
  • DONOR: Infection with HIV
  • DONOR: Inability to achieve adequate venous access
  • DONOR: Known allergy to filgrastim (G-CSF)
  • DONOR: Current serious systemic illness

Trial locations and contacts

3 sites in 2 countries.

3 sites in 2 countries

United States2 sites

  • Veterans Administration Center-Seattle

    Seattle, Washington, 98108

  • 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: Allogeneic Hematopoietic Stem Cell Transplantation With Nonmyeloablative Conditioning for Patients With Chronic Lymphocytic Leukemia - A Multi-center Trial

This clinical trial studies how well giving fludarabine phosphate together with total-body irradiation (TBI) before donor peripheral blood stem cell transplant works in treating patients with chronic lymphocytic leukemia or small lymphocytic leukemia. Giving low doses of chemotherapy, such as fludarabine phosphate, and TBI before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. Giving chemotherapy before or after peripheral blood stem cell transplant also stops the patient's immune system 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). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil before and after the transplant may stop this from happening.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine whether nonmyeloablative allogeneic hematopoietic stem cell transplantation (HSCT) from matched-related donors can improve the probability of survival 18 months after treatment for fludarabine (fludarabine phosphate)-refractory, fludarabine phosphate, cyclophosphamide, and rituximab (FCR)-failed, or del 17p chronic lymphocytic leukemia (CLL) beyond that observed in historical controls (30%).

SECONDARY OBJECTIVES:

  1. To assess the rate of relapse with allogeneic HSCT using nonmyeloablative conditioning for patients with fludarabine-refractory, FCR-failed, or del 17p CLL compared with historical data on autologous HSCT.

II. To estimate the incidence of grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD in patients with CLL treated with low-dose TBI, fludarabine, peripheral blood stem cell (PBSC) infusion and immunosuppression with cyclosporine and mycophenolate mofetil.

III. To characterize the rate and types of infections with this regimen.

IV. To estimate the rate of transplant-related mortality in the first 200 days.

OUTLINE:

NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2 and TBI on day 0.

TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant on day 0.

GVHD PROPHYLAXIS: Patients receive cyclosporine orally (PO) every 12 hours on days -3 to 180 with taper beginning on day 56 and mycophenolate mofetil PO every 12 hours on days 0-27.

After completion of study treatment, patients are followed up at 12 and 18 months and then annually for 5 years.

Being tested
Cyclosporine, Fludarabine Phosphate, Hematopoietic Cell Transplantation, Laboratory Biomarker Analysis, Mycophenolate Mofetil
Medical subject headings
Leukemia, Prolymphocytic, B-Cell, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Prolymphocytic, Leukemia, Prolymphocytic, T-Cell

What participants receive

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

  • CyclosporineDrug

    Also called 27-400, Ciclosporin, CsA, Cyclosporin

    Given PO

  • Fludarabine PhosphateDrug

    Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara

    Given IV

  • Hematopoietic Cell TransplantationProcedure or surgery

    Also called HCT, Hematopoietic Stem Cell Transplantation, HSCT, stem cell transplantation

    Undergo allogeneic peripheral blood stem cell transplant

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Mycophenolate MofetilDrug

    Also called Cellcept, MMF

    Given PO

  • Nonmyeloablative Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called Non-myeloablative allogeneic transplant, Nonmyeloablative Stem Cell Transplantation, NST

    Undergo allogeneic peripheral blood stem cell transplant

  • Total-Body IrradiationRadiation

    Also called TOTAL BODY IRRADIATION, Whole-Body Irradiation

    Undergo TBI

Study groups in NCT00060424
Study groupRoleWhat they receive
Treatment (enzyme inhibitor, transplant, GVHD prophylaxis)ExperimentalNONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and TBI on day 0. TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclosporine PO every 12 hours on days -3 to 180 with taper on day 56 and mycophenolate mofetil PO every 12 hours on days 0-27.
Receives: Drug: Cyclosporine; Drug: Fludarabine Phosphate; Procedure: Hematopoietic Cell Transplantation; Other: Laboratory Biomarker Analysis; Drug: Mycophenolate Mofetil; Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation; Radiation: Total-Body Irradiation

What is being measured

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

  1. Overall Survival

    Number of patients surviving 18 months post-transplant.

    Measured: At 18 months

Secondary outcomes (4)

  1. Rate of Relapse

    Number of patients with relapsed disease post-transplant. Relapse/progression is defined as 1) Physical exam/Imaging studies (nodes, liver, and/or spleen) ≥50% increase or new, 2) circulating lymphocytes by morphology and/or flow cytometry ≥50% increase, or 3) lymph node Biopsy Richter's transformation.

    Measured: 18 months

  2. Acute Grade II-IV GVHD and Chronic (Extensive) GVHD

    Number of patients who developed acute/chronic GVHD post-transplant. aGVHD Stages

    Skin:

    a maculopapular eruption involving < 25% BSA a maculopapular eruption involving 25 - 50% BSA generalized erythroderma generalized erythroderma with bullous formation and often with desquamation

    Liver:

    bilirubin 2.0 - 3.0 mg/100 mL bilirubin 3 - 5.9 mg/100 mL bilirubin 6 - 14.9 mg/100 mL bilirubin > 15 mg/100 mL

    Gut:

    Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall.

    aGVHD Grades Grade II: Stage 1 - 3 skin and/or stage 1 gut involvement and/or stage 1 liver involvement Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death

    Measured: aGVHD: 100 days after transplant; cGVHD: 1 Year after transplant.

  3. Rate and Types of Infections

    Number of infections patients experienced, by infection type.

    Measured: 18 months

  4. Transplant-related Mortality

    Defined as death before day +200 not related to progression of disease.

    Measured: At 200 days

Timeline

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

  1. First posted7 May 2003 (estimated)
  2. Study startMar 2003
  3. Primary completionSep 2010
  4. Study completion22 Sep 2010

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
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00060424
Sponsor's protocol ID
1711.00
Other IDs
NCI-2010-01276, NCI-2011-01116, 1711.00, P30CA015704
Status last verified
Dec 2017
First submitted
6 May 2003
Last updated
8 Dec 2017
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 Cyclosporine, Fludarabine Phosphate and Hematopoietic Cell Transplantation in people with B-Cell Prolymphocytic Leukemia and Chronic Lymphocytic Leukemia, run by Fred Hutchinson Cancer Center at 3 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 9 inclusion and 20 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 8 Dec 2017. 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, 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 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 8 Dec 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?

Overall Survival (time frame: At 18 months). 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 NCT00060424, 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 8 Dec 2017.

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