Ofatumumab Induction and Maintenance in Elderly Patients With Poor Risk CLL in the Context of Allogeneic Transplantation(CLL-X4 Trial)
Overview
- Phase
- Phase 2
- Intervention
- Ofatumumab
- Conditions
- Chronic Lymphatic Leukemia
- Sponsor
- Technische Universität Dresden
- Enrollment
- 20
- Locations
- 11
- Primary Endpoint
- rate of MRD-negative patients
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
To study the safety and efficacy of anti-CD20 blockade with ofatumumab in the context of allogeneic HCT in CLL
Detailed Description
The goal of the study is to investigate the safety and efficacy of a consequent anti-CD20 therapy with the antibody ofatumumab in the context of allogeneic HCT. Allogeneic HCT itself is not a study intervention and is triggered by the availability of an HLA-compatible stem cell donor. The study is divided into an induction part and a maintenance part. During induction where the antibody is combined with high dose dexamethasone, the main goal is to reduce the tumor load prior to allogeneic HCT. Patients who achieved disease control (CR, PR and SD) by the antibody proceed to maintenance therapy with the antibody. Patients with progressive disease go off study. The idea behind maintenance therapy is that ofatumumab may contribute to tumor control early after allogeneic stem cell transplantation while T-cell based graft-versus leukemia effects are still not fully established. External tumor control could lower the pressure to taper immunosuppressive drugs early after transplantation and could thereby indirectly contribute to better GVHD-prophylaxis. Furthermore, anti-CD20 antibodies have proven activity in the treatment of chronic GVHD. In summary, the concept of a consequent CD20 blockade in the context of allogeneic transplantation could result in better leukemic control and better GVHD prophylaxis, which is a highly attractive goal.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Diagnosis of CLL according to WHO criteria (Hallek 2008) confirmed by flow cytometry of peripheral blood or bone marrow
- •Age \> 55 years
- •Poor-risk disease according to the EBMT CLL Transplant Consensus
- •Non-response or early relapse (within 12 months) after purine analogue-containing therapy
- •Relapse (within 24 months) after purine analogue combination therapy or treatment of similar efficacy (ie, autologous stem cell transplantation)
- •p53 deletion/mutation (del 17p-) requiring treatment
- •Measurable disease in the peripheral blood defined by a minimum clonal lymphocyte count of 0.5 GPT/L at the time of study inclusion
- •Medically fit patients eligible for allogeneic HCT
- •Informed consent for related and unrelated donor search and the goal to perform allogeneic HCT
- •Sexually mature males must agree to use adequate and medically accepted method of contraception throughout the study if their sexual partners are woman of child bearing potential (WOCBP) WOCBP must be using an adequate and medically accepted method of contraception to avoid pregnancy throughout the study and for at least 3 months after the study.
Exclusion Criteria
- •Richter's transformation in current relapse or active disease
- •Prior allogeneic HCT
- •Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to enrollment, whichever is longer, or participation in any other interventional clinical study
- •Non-response to monotherapy with ofatumumab prior to study inclusion
- •Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (left ventricular ejection fraction \< 50%)
- •Abnormal renal function defined by an estimated GFR \< 50 ml/min
- •Abnormal lung function tests defined by a DLCO \<50%, FEV1%VC \<70% despite appropriate treatment
- •Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg or HBcAb
- •Positive serology for hepatitis C (HC) defined as a positive test for anti-HCV, confirmed by PCR
- •Screening laboratory values:
Arms & Interventions
Ofatumumab
First dose of 300 mg Ofatumumab followed by seven weekly infusions of 2000 mg. Dexamethasone will be given orally at doses of 40 mg on days 1-4 in weeks 1, 3, 5, and 7. Maintenance therapy consists of 6 monthly infusions of 1000 mg ofatumumab.
Intervention: Ofatumumab
Outcomes
Primary Outcomes
rate of MRD-negative patients
Time Frame: baseline, week 9, month 14
rate of MRD-negative patients who did not experience relapse, progression or death within the first 14 months after study enrollment
Response rate after induction therapy
Time Frame: week 9
efficacy analysis of anti-CD20 blockade with ofatumumab
Secondary Outcomes
- adverse drug reactions grade III/IV(week 1 till week 9; month 4 till month 9; month 12; month 14; until 30 days after last administration of the study medication)
- Rate of allogeneic HCT(month 9)
- Overall, event-, and progression free survival(week 1 till week 9; month 4 till month 9; month 12; month 14; up to 5 years follow-up)
- relapse incidence(month 4 till month 9; month 12; month 14; up to 5 years follow-up)
- non-relapse mortality(week 1 till week 9; month 4 till month 9; month 12; month 14; up to 5 years follow-up)
- Incidences of acute and chronic GVHD(during maintenance therapy; month 12, month 14; up to 5 years follow-up)