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Chronic Lymphocytic LeukemiaPhase 1/2NCT00281983

Fludarabine and Cyclophosphamide in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Chronic Lymphocytic Leukemia or Waldenstrom's Macroglobulinemia

A Phase 1/2 study testing alemtuzumab, anti-thymocyte globulin and filgrastim in people with Chronic Lymphocytic Leukemia, run by German CLL Study Group at 13 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

RATIONALE: Giving chemotherapy before a donor bone marrow transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Chronic Lymphocytic Leukemia
What is being tested?
alemtuzumab, anti-thymocyte globulin and filgrastim
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
13 sitesin 2 countries
Study dates
Jun 2000to Jul 2010
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 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

DISEASE CHARACTERISTICS:

  • Diagnosis of B-cell chronic lymphocytic leukemia or lymphoplasmocytic lymphoma (Waldenstrom's macroglobulinemia)
  • Must have poor prognostic features and low probability of successful autografting, defined by one of the following criteria:
  • Progressive disease with unfavorable cytogenetics (deletion or mutation of critical regions on chromosomes 11q and/or 17p [p53]; and/or unmutated status of the immunoglobulin V_H gene region; and/or usage of the V_H 3-21 gene), defined as 1 of the following:
  • Doubling of lymphocyte count or nodal involvement within 3 months or less
  • Progressive decline of platelet count and/or hemoglobin values defining Binet stage C disease (or to 50% or less of baseline values within 3 months) not due to immune mechanisms
  • Symptomatic splenomegaly
  • Discomfort or imminent complications due to large tumor masses
  • B symptoms
  • Refractory disease or early relapse (within 12 months) after treatment with a fludarabine-containing regimen
  • Relapsed after autologous stem cell transplant (SCT)
  • Insufficient stem cell harvest for intended autologous SCT
  • Presence of a clonal CDR III rearrangement detected by polymerase chain reaction
  • No Richter's syndrome
  • HLA-identical sibling or unrelated donor available

PATIENT CHARACTERISTICS:

  • ECOG performance status ≤ 1
  • Creatinine clearance > 60 mL/min
  • SGOT, SGPT, and bilirubin < 2 times normal
  • Normal cardiac function determined by ECG and echocardiographic examination
  • Inspiratory vital capacity, FEV_1, and DLCO > 50% of predicted
  • No serious localized or systemic infections
  • No other concurrent malignant disease
  • No impaired organ function
  • No uncontrolled diabetes
  • No uncontrolled hypertension
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No HIV infection
  • No hepatitis B or C infection
  • No concurrent alcohol or drug abuse
  • No dementia or altered mental status that would preclude giving informed consent

PRIOR CONCURRENT THERAPY:

  • Not specified

Trial locations and contacts

13 sites in 2 countries.

13 sites in 2 countries

Germany12 sites

  • Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin

    Berlin, 12200

  • Universitaetsklinikum Essen

    Essen, 45122

  • Universitaetsklinikum Goettingen

    Göttingen, 37075

  • Asklepios Klinik St. Georg

    Hamburg, D-20099

  • Medizinische Hochschule Hannover

    Hanover, 30625

  • Universitaets-Kinderklinik Heidelberg

    Heidelberg, D-69120

  • Universitaetsklinikum des Saarlandes

    Homburg, 66421

  • Clinic for Bone Marrow Transplantation and Hematology and Oncology

    Idar-Oberstein, D-55743

  • University Hospital Schleswig-Holstein - Kiel Campus

    Kiel, 24116

  • University Hospital of Leipzig

    Leipzig, 04103

  • Klinikum der Universitaet Regensburg

    Regensburg, 93053

  • Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm

    Ulm, 89081

Other trials in Germany

Canada1 site

  • Maisonneuve-Rosemont Hospital

    Montreal, Quebec, H1T 2M4

Other trials in Canada

About this study

Official title: Pilot Study on Allogeneic Stem Cell Transplantation Following Conditioning With Fludarabine and an Alkylating Agent in Patients With High-Risk Chronic Lymphocytic Leukemia

RATIONALE: Giving chemotherapy before a donor bone marrow transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. Also, monoclonal antibodies, such as alemtuzumab, can find cancer cells and either kill them or deliver cancer-killing substances to them without harming normal 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. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving methotrexate, cyclosporine and mycophenolate mofetil after the transplant may stop this from happening. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them (called graft-versus-tumor effect). Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) may boost this effect.

PURPOSE: This phase I/II trial is studying the side effects of giving fludarabine together with cyclophosphamide and to see how well they work in treating patients who are undergoing donor stem cell transplant for B-cell chronic lymphocytic leukemia or Waldenström's macroglobulinemia.

Read the detailed description

OBJECTIVES:

Primary

  • Determine the feasibility and safety of induction therapy comprising fludarabine and cyclophosphamide followed by allogeneic stem cell transplantation in patients with high-risk B-cell chronic lymphocytic leukemia or lymphoplasmocytic lymphoma (Waldenstrom's macroglobulinemia).

Secondary

  • Determine the incidence and kinetics of clinical and molecular remissions in patients treated with this regimen.
  • Determine event-free and overall survival of patients treated with this regimen.
  • Determine the duration of clinical and molecular remission in relation to the underlying cytogenetic deviation in patients treated with this regimen.
  • Determine the kinetics and extent of lympho-hematopoietic donor chimerism in patients treated with this regimen.

OUTLINE: This is a multicenter, open-label, nonrandomized, pilot study.

  • Cytoreductive therapy: Patients receive up to 3 courses of cytoreductive therapy comprising fludarabine IV and cyclophosphamide IV on days 1-3 (with or without rituximab IV on day 1). Patients refractory to fludarabine-containing therapy may receive alemtuzumab IV for 12 weeks OR any other cytotoxic salvage regimen for cytoreduction.
  • Conditioning regimen: Patients receive 1 of the following conditioning regimens*:

NOTE: *Patients who did not achieve partial response after cytoreductive therapy receive regimen 3.

  • Regimen 1: Patients receive fludarabine IV and cyclophosphamide IV on days -7 to -3. If stem cells are collected from an unrelated donor, patients also receive anti-thymocyte globulin (ATG) IV on days -4 to -1.
  • Regimen 2: Patients undergo total-body irradiation on day -9. Patients then receive alemtuzumab IV on days -8 to -4 and fludarabine IV and cyclophosphamide IV on days -6 to -2.
  • Regimen 3: Patients receive fludarabine IV on days -7 to -3, busulfan IV or orally on days -7 to -5, and cyclophosphamide IV on days -3 to -2. If stem cells are collected from an unrelated donor, patients also receive ATG on days -3 to -1.
  • Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo allogeneic PBSCT on day 0. Patients receive filgrastim (G-CSF) subcutaneously daily starting on day 5 and continuing until blood count recover.
  • Graft-versus-host-disease (GVHD) prophylaxis: Patients receive cyclosporine IV beginning on day -1 and continuing until approximately day 100. Patients treated with conditioning regimen 1 or 3 also receive methotrexate IV on days 1, 3, and 6 OR oral mycophenolate mofetil twice daily on days 0-50. Patients with evidence of residual disease at least 4 weeks after completion of cyclosporine undergo donor lymphocyte infusion (DLI).
  • DLI: The donor T-lymphocytes are collected from the PBSCT donor without prior G-CSF mobilization. Patients receive DLI every 8 weeks in the presence of residual disease and the absence of GVHD.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study.

Being tested
alemtuzumab, anti-thymocyte globulin, filgrastim, rituximab, therapeutic allogeneic lymphocytes
Keywords
B-cell chronic lymphocytic leukemia, refractory chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, Waldenström macroglobulinemia
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Waldenstrom Macroglobulinemia

What participants receive

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

Study groups in NCT00281983
Study groupRoleWhat they receive
Allogeneic stem cell transplantationExperimental1. Cytoreductive therapy for inducing a state of partial remission: FC or FC-R or alternative salvage regimens (e.g. Alemtuzumab) 2. Conditioning regimen: FC +/- ATG (Arm A) or FC/Busulfan +/- ATG (Arm C: refractory patients only) 3. allogeneic-PBSCT (from HLA-identical donor) 4. GVHD prophylaxis: CSA + MTX or MMF 5. +/- DLI (Donor lymphocyte infusions)
Receives: Biological: alemtuzumab; Biological: anti-thymocyte globulin; Biological: filgrastim; Biological: rituximab; Biological: therapeutic allogeneic lymphocytes; Drug: busulfan; Drug: cyclophosphamide; Drug: cyclosporine; Drug: fludarabine phosphate; Drug: methotrexate; Drug: mycophenolate mofetil; Procedure: peripheral blood stem cell transplantation; Radiation: radiation therapy

What is being measured

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

  1. Feasibility as measured by the proportion of eligible patients completing the transplant procedure successfully

  2. Safety as measured by a treatment-related mortality of < 25% at 2 years following transplant

Secondary outcomes (4)

  1. Clinical remission rate by NIH criteria at 12 months following transplant

  2. Minimal residual disease negativity rate as measured by high-resolution flow or CDR PCR at 12 months following transplant

  3. Chimerism as measured by STR-PCR at 12 months following transplant

  4. Event-free and overall survival at 5 years following transplant

Timeline

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

  1. First posted25 Jan 2006 (estimated)
  2. Study startJun 2000
  3. Study completionJul 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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
100 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00281983
Sponsor's protocol ID
CLL3X
Other IDs
EU-20554, MEDAC-FLUD.10/CLL
Status last verified
Apr 2007
First submitted
24 Jan 2006
Last updated
24 Jul 2017
Results posted
No
Individual data sharing
No

Publications

  • Dreger P, Dohner H, Ritgen M, Bottcher S, Busch R, Dietrich S, Bunjes D, Cohen S, Schubert J, Hegenbart U, Beelen D, Zeis M, Stadler M, Hasenkamp J, Uharek L, Scheid C, Humpe A, Zenz T, Winkler D, Hallek M, Kneba M, Schmitz N, Stilgenbauer S; German CLL Study Group. Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial. Blood. 2010 Oct 7;116(14):2438-47. doi: 10.1182/blood-2010-03-275420. Epub 2010 Jul 1.

    PubMed 20595516

  • Ritgen M, Bottcher S, Stilgenbauer S, Bunjes D, Schubert J, Cohen S, Humpe A, Hallek M, Kneba M, Schmitz N, Dohner H, Dreger P; German CLL Study Group. Quantitative MRD monitoring identifies distinct GVL response patterns after allogeneic stem cell transplantation for chronic lymphocytic leukemia: results from the GCLLSG CLL3X trial. Leukemia. 2008 Jul;22(7):1377-86. doi: 10.1038/leu.2008.96. Epub 2008 Apr 17.

    PubMed 18418404

  • Dreger P, Schnaiter A, Zenz T, Bottcher S, Rossi M, Paschka P, Buhler A, Dietrich S, Busch R, Ritgen M, Bunjes D, Zeis M, Stadler M, Uharek L, Scheid C, Hegenbart U, Hallek M, Kneba M, Schmitz N, Dohner H, Stilgenbauer S. TP53, SF3B1, and NOTCH1 mutations and outcome of allotransplantation for chronic lymphocytic leukemia: six-year follow-up of the GCLLSG CLL3X trial. Blood. 2013 Apr 18;121(16):3284-8. doi: 10.1182/blood-2012-11-469627. Epub 2013 Feb 22.

    PubMed 23435461

  • Scheffold A, Jebaraj BMC, Jaramillo S, Tausch E, Steinbrecher D, Hahn M, Bottcher S, Ritgen M, Bunjes D, Zeis M, Stadler M, Uharek L, Scheid C, Hegenbart U, Hallek M, Kneba M, Schmitz N, Dohner H, Dreger P, Stilgenbauer S. Impact of telomere length on the outcome of allogeneic stem cell transplantation for poor-risk chronic lymphocytic leukaemia: results from the GCLLSG CLL3X trial. Br J Haematol. 2017 Oct;179(2):342-346. doi: 10.1111/bjh.14219. Epub 2016 Jul 8. No abstract available.

    PubMed 27391907

  • Kramer I, Stilgenbauer S, Dietrich S, Bottcher S, Zeis M, Stadler M, Bittenbring J, Uharek L, Scheid C, Hegenbart U, Ho A, Hallek M, Kneba M, Schmitz N, Dohner H, Dreger P. Allogeneic hematopoietic cell transplantation for high-risk CLL: 10-year follow-up of the GCLLSG CLL3X trial. Blood. 2017 Sep 21;130(12):1477-1480. doi: 10.1182/blood-2017-04-775841. Epub 2017 Jul 17. No abstract available.

    PubMed 28716861

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing alemtuzumab, anti-thymocyte globulin and filgrastim in people with Chronic Lymphocytic Leukemia, run by German CLL Study Group at 13 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?

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 24 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Germany, Canada. 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?

Feasibility as measured by the proportion of eligible patients completing the transplant procedure successfully. The study lists 2 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 NCT00281983, which also lists 5 linked publications.

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 24 Jul 2017; AzTrials last refreshed its copy on 7 Nov 2026.

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