Alemtuzumab in Treating Patients With B-Cell Chronic Lymphocytic Leukemia

NCT ID: NCT00634881

Last Updated: 2019-06-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-11-30
• Study Completion Date: 2012-02-17

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.

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.

Conditions

Chronic Lymphocytic Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A: Alemtuzumab i.v.

Intravenous administration of alemtuzumab according to the 3 + 3 dose escalation design.

Group Type: EXPERIMENTAL

Alemtuzumab i.v.

Intervention Type: 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)

Cohort B: Alemtuzumab s.c.

After 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.

Group Type: EXPERIMENTAL

Alemtuzumab s.c.

Intervention Type: 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)

Interventions

Alemtuzumab i.v.

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)

Intervention Type: BIOLOGICAL

Alemtuzumab s.c.

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)

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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

• 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

Exclusion Criteria

• 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
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

German CLL Study Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Hallek, MD

Role: STUDY_CHAIR

Medizinische Universitaetsklinik I at the University of Cologne

Locations

Medizinische Universitaetsklinik I at the University of Cologne

Cologne, , Germany

Klinikum Barnim GmbH, Werner Forssmann Krankenhaus

Eberswalde, , Germany

Universitatsklinikum Heidelberg

Heidelberg, , Germany

Klinikum Lippe - Lemgo

Lemgo, , Germany

III Medizinische Klinik Mannheim

Mannheim, , Germany

Krankenhaus Barmherzige Brueder Regensburg

Regensburg, , Germany

Countries

Germany

References

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.

Reference Type: RESULT

PMID: 27862308 (View on PubMed)

Other Identifiers

CDR0000587746

Identifier Type: OTHER

Identifier Source: secondary_id

CLL2i

Identifier Type: -

Identifier Source: org_study_id