Subcutaneous Alemtuzumab Combined With Oral Dexamethasone, Followed by Alemtuzumab Maintenance or Allo-SCT in CLL With 17p- or Refractory to Fludarabine

• Status: Completed
• Trial end date: 2016-03-01
• Target enrollment: 0
• Participant gender: All

Summary

Aims and objectives

• Assessment of the efficacy of the study treatment in the study population in terms of response rate, progression-free survival, failure-free survival and overall survival.

• Acquisition of further data to expand the data base on the toxicity of the study treatment.

• Assessment of the efficacy of the study treatment in biological risk groups.

• Assessment of response in terms of minimal residual disease. Number of patients and estimated duration Total no. of patients: 122 (~29 with 17p deletion for first-line therapy, ~29 with 17p deletion for second- or higher-line treatment, ~65 fludarabine-refractory irrespective of 17p status).

Duration for each patient: Max. 12 weeks of treatment in three 4-week cycles, then up to two years maintenance treatment.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Ulm
• Collaborators: German CLL Study Group; IMSE, TU Munich (Biometry); Technische Universität München; WiSP Wissenschaftlicher Service Pharma GmbH
• Treatments: Alemtuzumab; BB 1101; Dexamethasone; Dexamethasone 21-phosphate; Dexamethasone acetate; Fludarabine; Fludarabine phosphate; Vidarabine

Criteria

Inclusion Criteria:

1. The patient has CLL requiring treatment (Binet C or A/B with "active disease" according to the NCI criteria).

2. One or both of the following is true:

• The patient's disease is refractory to a previous fludarabine-containing regimen, defined as no CR or PR according to NCI criteria, or progression within 6 months after a fludarabine-containing regime. (N.B.: Within the framework of this trial, the term "fludarabine-refractory" is synonymous to a refractory status to any established purine analogue (i.e. pentostatin, cladribine); this also encompasses bendamustine, as this drug molecule contains both an alkylating and a purine analogue moiety. Acc. to experimental findings and clinical experience, its mechanism of action differs distinctly from that of a pure alkylator (Cheson et al., 2009, Leoni et al., 2008)).

• 17p deletion is present (irrespective of whether previously treated or untreated).

3. The patient is at least 18 years of age.

4. The patient's performance status is 0, 1 or 2 on the WHO/ECOG scale.

5. Any previous chemotherapy and/or immunotherapy ended at least four weeks before the first study treatment with alemtuzumab.

6. The patient has recovered from all previous chemotherapy and/or immunotherapy.

7. For fertile men and for women of childbearing potential: Adequate contraception (oral contraceptives, intrauterine device or barrier method in conjunction with spermicidal jelly).

8. The patient has given written informed consent to participate in the study.

Exclusion Criteria:

1. The patient has received more than five different prior therapeutic regimens.

2. Any major organ dysfunction is present (e.g. unstable angina pectoris, NYHA III/IV heart insufficiency, significant coronary stenoses, uncontrolled diabetes mellitus, uncontrolled hypertension, pulmonary disease with hypoxemia, renal failure).

3. Any of the following laboratory values are found at the screening visit to be >2 × the upper limit of the normal range: serum creatinine, serum bilirubin, ASAT, ALAT.

4. Any active infection is present.

5. B-PLL or Richter transformation is diagnosed or suspected (e.g. symptoms or cytology).

6. There is involvement of the central nervous system.

7. The patient is known to be positive for human immunodeficiency virus (HIV).

8. CMV viremia is present, as demonstrated by pp65 EA or CMV-DNA.

9. The patient has previously been treated with alemtuzumab. (Exception: alemtuzumab used in a "non-therapeutic" context, i.e. administered as part of a conditioning regimen prior to SCT).

10. The patient has received autologous or allogeneic SCT within the past six months.

11. The patient is receiving long-term systemic treatment with corticosteroids or has received such treatment in the four weeks before first treatment with alemtuzumab.

12. Any additional active malignancy is present.

13. The patient has ever had an anaphylactic response to humanized antibodies.

14. For female patients: The patient is pregnant or lactating.

15. The patient has a history of drug or alcohol abuse that might lead to inability to comply with the protocol.