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Chronic Lymphocytic LeukemiaPhase 1/2NCT00634881

Alemtuzumab in Treating Patients With B-Cell Chronic Lymphocytic Leukemia

A Phase 1/2 study testing Alemtuzumab i.v. and Alemtuzumab s.c. in people with Chronic Lymphocytic Leukemia, run by German CLL Study Group at 6 sites in Germany.

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

RATIONALE: Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Lymphocytic Leukemia
What is being tested?
Alemtuzumab i.v. and Alemtuzumab s.c.
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
6 sitesGermany
Study dates
Nov 2003to 17 Feb 2012
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of B-cell chronic lymphocytic leukemia (B-CLL)
  • Disease in complete or partial remission after completion of 4-6 courses of second-line cytoreductive therapy no less than 90 days and no more than 150 days ago
  • Second-line cytoreductive therapy must comprise 1 of the following regimens:
  • Fludarabine phosphate alone (F)
  • Fludarabine phosphate and cyclophosphamide (FC)
  • Fludarabine phosphate, cyclophosphamide, and rituximab (FCR)
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  • Bendamustine hydrochloride alone (B)
  • Bendamustine hydrochloride and rituximab chemotherapy (BR)
  • Complete minimal residual disease response defined by the following:
  • At least negativity of 4-color-cytometry and/or even PCR-amplifiable clonal CDR III rearrangement of the IgV_H
  • For PCR analysis, blood sample need to be taken at beginning or during second-line cytoreductive therapy before achievement of a clinical complete remission
  • Disease not refractory to first-line F/FC/FCR/B/BR if received such therapy
  • ECOG performance status 0-1
  • ANC ≥ 1,500/µL
  • Platelets ≥ 50,000/µL
  • Creatinine ≤ 1.5 times the upper normal limit (ULN)
  • Conjugated bilirubin ≤ 2 times ULN
  • Thyroid function normal
  • Not pregnant or nursing
  • Fertile patients must use effective contraception

Who cannot join

  • Presence of bulky lymph nodes (> 5 cm) after second-line F/FC/FCR/B/BR
  • Clinically apparent autoimmune cytopenia (i.e., autoimmune hemolytic anemia, autoimmune thrombocytopenia, or pure red cell aplasia)
  • CNS involvement with B-CLL
  • PATIENT CHARACTERISTICS:
  • Severe infection during second-line treatment with F/FC/FCR/B/BR, meeting any 1 of the following criteria:
  • Any episode of NCI grade 4 infection
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  • More than 1 episode of NCI grade 3 infection
  • Medical condition requiring long-term use of oral corticosteroids for more than 1 month
  • Active bacterial, viral, or fungal infection
  • HIV, hepatitis B virus, and/or hepatitis C virus-positive serum status
  • Concurrent severe diseases that exclude the administration of protocol therapy, including any of the following:
  • NYHA class III-IV heart insufficiency
  • Severe chronic obstructive lung disease with hypoxemia
  • Severe ischemic cardiac disease
  • Active secondary malignancy other than B-CLL prior to the study
  • Known hypersensitivity or anaphylactic reaction against murine proteins or one of the drug components
  • PRIOR CONCURRENT THERAPY:
  • See Disease Characteristics
  • No more than 2 prior chemotherapies, including F/FC/FCR/B/BR therapy
  • No more than 1 pretreatment (before second-line therapy) with chlorambucil or F/FC/FCR/B/BR
  • No chemotherapy or radiotherapy for any neoplastic disease other than B-CLL prior to the study

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

Germany6 sites

  • Medizinische Universitaetsklinik I at the University of Cologne

    Cologne, D-50924

  • Klinikum Barnim GmbH, Werner Forssmann Krankenhaus

    Eberswalde, 16225

  • Universitatsklinikum Heidelberg

    Heidelberg, D-69115

  • Klinikum Lippe - Lemgo

    Lemgo, D-32657

  • III Medizinische Klinik Mannheim

    Mannheim, D-68305

  • Krankenhaus Barmherzige Brueder Regensburg

    Regensburg, D-93049

Other trials in Germany

About this study

Official title: Consolidation Therapy With Alemtuzumab (MabCampath®) in Patients With Chronic Lymphocytic Leukemia Who Are in Complete or Partial 2nd Remission After Cytoreduction With Fludarabine or Fludarabine Plus Cyclophosphamide or Fludarabine Plus Cyclophosphamide Plus Rituximab or Bendamustine or Bendamustine Plus Rituximab - a Phase I/II Study

RATIONALE: Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them.

PURPOSE: This phase I/II trial is studying the side effects and best dose of alemtuzumab in treating patients with B-cell chronic lymphocytic leukemia.

Read the detailed description

OBJECTIVES:

  • To determine the safest dose of alemtuzumab as consolidation therapy in patients in second remission after fludarabine phosphate alone; fludarabine phosphate and cyclophosphamide; fludarabine phosphate, cyclophosphamide, and rituximab; bendamustine hydrochloride alone; or bendamustine hydrochloride and rituximab.
  • To determine the frequency of cytomegalovirus reactivations or infections during or after alemtuzumab treatment.
  • To determine which dose of alemtuzumab is efficient to eliminate minimal residual disease in peripheral blood and bone marrow (i.e., to turn a clinical partial remission into a clinical complete remission [CR], to turn a flow cytometry-positive CR into a flow cytometry-negative CR, or to turn a PCR-positive CR into a PCR-negative CR).
  • To determine the pharmacokinetic profile of alemtuzumab.
  • To compare the pharmacokinetic profile between intravenous versus subcutaneous administration of alemtuzumab.

OUTLINE: This is a multicenter, dose-escalation study of alemtuzumab.

  • Group 1: Patients receive escalating doses of alemtuzumab IV over 2 hours once weekly for 8 weeks until the maximum tolerated dose (MTD) is determined.
  • Group 2: Patients receive escalating doses of alemtuzumab subcutaneously once weekly for 8 weeks, beginning with the MTD determined in group 1 until a second MTD is determined.

Patients undergo bone marrow and blood sample collection periodically for laboratory and pharmacokinetic studies. Samples are analyzed for minimal residual disease and T-cell subsets (i.e., CD4 and CD8) via quantitative-PCR analysis and flow cytometry and cytomegalovirus antigens via PCR.

After completion of study treatment, patients are followed at 3, 6, 9, 12, 18, and 24 months.

Being tested
Alemtuzumab i.v., Alemtuzumab s.c.
Keywords
B-cell chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

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

  • Alemtuzumab i.v.Biological

    Alemtuzumab will be administered once per week as a 2 h infusion

    • Dose level I: 10mg once weekly (start with dose escalation : 3 mg on day 1, 10mg on day 2) Duration
    • Dose level II: 20mg once weekly (start with dose escalation: 3mg on day 1, 10mg on day 2, 20mg on day 3)
    • Dose level III: 30mg once weekly (start with dose escalation: 3mg on day 1, 10mg on day 2, 30mg on day 3)

  • Alemtuzumab s.c.Biological

    Alemtuzumab will be administered once per week subcutaneously

    • Dose level I: 10mg once weekly (start with dose escalation : 3 mg on day 1, 10mg on day 2) Duration
    • Dose level II: 20mg once weekly (start with dose escalation: 3mg on day 1, 10mg on day 2, 20mg on day 3)
    • Dose level III: 30mg once weekly (start with dose escalation: 3mg on day 1, 10mg on day 2, 30mg on day 3)
Study groups in NCT00634881
Study groupRoleWhat they receive
Cohort A: Alemtuzumab i.v.ExperimentalIntravenous administration of alemtuzumab according to the 3 + 3 dose escalation design.
Receives: Biological: Alemtuzumab i.v.
Cohort B: Alemtuzumab s.c.ExperimentalAfter i.v. MTD (maximum tolerable dosage) has been determined, subcutaneous dose escalation is performed according to the same escalation rules as for cohort A, starting with the recommended dose level of i.v. application.
Receives: Biological: Alemtuzumab s.c.

What is being measured

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

  1. Dose-limiting toxicity

    • Dose-limiting toxicity (DLT) and maximal tolerable dose (MTD) DLT is defined as a) all grade III/IV non-hematologic toxicity and b) all grade IV hematologic toxicity lasting for more than 2 weeks (excluding lymphopenia) occuring during or within 4 weeks after end of consolidation therapy.

    Measured: 28 days after the last dose of study medication

  2. Maximum tolerated dose

    • Dose-limiting toxicity (DLT) and maximal tolerable dose (MTD) DLT is defined as a) all grade III/IV non-hematologic toxicity and b) all grade IV hematologic toxicity lasting for more than 2 weeks (excluding lymphopenia) occuring during or within 4 weeks after end of consolidation therapy.

    Measured: 28 days after the last dose of study medication

Secondary outcomes (8)

  1. Rate of complete minimal residual disease response

    • Rate of molecular responses (defined by negativity of 4- colour- cytometry in BOTH peripheral blood AND bone marrow in patients in clinical CR) The approved laboratory diagnostics for detection of MRD response is 4-colour flow cytometry. Collaterally, it is possible to take samples for potential PCR- analysis for confirmation if available.

    Measured: will be tested repeatedly, first time 3 months after the last dose of study medication, last time point 24 months after last dose of study medication

  2. Rate of immunophenotypic remission using 4-color flow cytometry

    Measured: will be tested repeatedly, first time 3 months after the last dose of study medication,

  3. Rate of infections (especially CMV infections and reactivations)

    Measured: upt to 24 months after last dose of study medication (end of study)

  4. Rate of severe hematologic and non-hematologic side effects

    Measured: 28 days after the last dose of study medication

  5. Pharmacokinetics of alemtuzumab (after IV and subcutaneous administration)

    Pharmacokinetic samples will be taken at week 4 and 8 during alemtuzumab treatment at the following time points: 0, 4, 8, 24, 48, 96, 168 h

    Measured: up to 8 weeks during the alemtuzumab treatment

  6. Progression-free survival

    Measured: upt to 24 months after last dose of study medication (end of study)

  7. Overall survival

    Measured: upt to 24 months after last dose of study medication (end of study)

  8. Complete remission rate

    Measured: 28 days after the last dose of study medication

Timeline

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

  1. First posted13 Mar 2008 (estimated)
  2. Study startNov 2003
  3. Primary completionJan 2010
  4. Study completion17 Feb 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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00634881
Sponsor's protocol ID
CLL2i
Other IDs
CDR0000587746
Status last verified
Jun 2019
First submitted
12 Mar 2008
Last updated
13 Jun 2019
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Al-Sawaf O, Fischer K, Herling CD, Ritgen M, Bottcher S, Bahlo J, Elter T, Stilgenbauer S, Eichhorst BF, Busch R, Elberskirch U, Abenhardt W, Kneba M, Hallek M, Wendtner CM. Alemtuzumab consolidation in chronic lymphocytic leukaemia: a phase I/II multicentre trial. Eur J Haematol. 2017 Mar;98(3):254-262. doi: 10.1111/ejh.12825. Epub 2016 Dec 1.

    PubMed 27862308

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Alemtuzumab i.v. and Alemtuzumab s.c. in people with Chronic Lymphocytic Leukemia, run by German CLL Study Group at 6 sites in Germany.

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 20 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 13 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Germany. 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?

Dose-limiting toxicity (time frame: 28 days after the last dose of study medication). 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 NCT00634881, 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 13 Jun 2019.

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