Alemtuzumab in Treating Patients With B-Cell Chronic Lymphocytic Leukemia
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
2 other identifiers
interventional
13
1 country
6
Brief 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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Nov 2003
Longer than P75 for phase_1
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 1, 2003
CompletedFirst Submitted
Initial submission to the registry
March 12, 2008
CompletedFirst Posted
Study publicly available on registry
March 13, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2010
CompletedStudy Completion
Last participant's last visit for all outcomes
February 17, 2012
CompletedJune 13, 2019
June 1, 2019
6.2 years
March 12, 2008
June 12, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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.
28 days after the last dose of study medication
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.
28 days after the last dose of study medication
Secondary Outcomes (8)
Rate of complete minimal residual disease response
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
Rate of immunophenotypic remission using 4-color flow cytometry
will be tested repeatedly, first time 3 months after the last dose of study medication,
Rate of infections (especially CMV infections and reactivations)
upt to 24 months after last dose of study medication (end of study)
Rate of severe hematologic and non-hematologic side effects
28 days after the last dose of study medication
Pharmacokinetics of alemtuzumab (after IV and subcutaneous administration)
up to 8 weeks during the alemtuzumab treatment
- +3 more secondary outcomes
Study Arms (2)
Cohort A: Alemtuzumab i.v.
EXPERIMENTALIntravenous administration of alemtuzumab according to the 3 + 3 dose escalation design.
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.
Interventions
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 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)
Eligibility Criteria
You may qualify if:
- 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)
- 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
You may not qualify if:
- 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:
- 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
- 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
- More than 1 episode of NCI grade 3 infection
- +14 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (6)
Medizinische Universitaetsklinik I at the University of Cologne
Cologne, D-50924, Germany
Klinikum Barnim GmbH, Werner Forssmann Krankenhaus
Eberswalde, 16225, Germany
Universitatsklinikum Heidelberg
Heidelberg, D-69115, Germany
Klinikum Lippe - Lemgo
Lemgo, D-32657, Germany
III Medizinische Klinik Mannheim
Mannheim, D-68305, Germany
Krankenhaus Barmherzige Brueder Regensburg
Regensburg, D-93049, Germany
Related Publications (1)
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.
PMID: 27862308RESULT
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Michael Hallek, MD
Medizinische Universitaetsklinik I at the University of Cologne
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 12, 2008
First Posted
March 13, 2008
Study Start
November 1, 2003
Primary Completion
January 1, 2010
Study Completion
February 17, 2012
Last Updated
June 13, 2019
Record last verified: 2019-06
Data Sharing
- IPD Sharing
- Will not share