Ofatumumab Induction and Maintenance in Elderly Patients With Poor Risk CLL in the Context of Allogeneic Transplantation

NCT01809847 | Completed Phase 2

• 2 other identifiers: TUD-CLL-X4-0542012-001947-31
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 11

Brief Summary

To study the safety and efficacy of anti-CD20 blockade with ofatumumab in the context of allogeneic HCT in CLL

Conditions

Chronic Lymphatic Leukemia

Keywords

CLL; Chronic Lymphatic Leukemia; Leukemia; HLA; Histocompatibility; HCT; hematopoietic stem cell transplantation; Ofatumumab; CD20

Outcome Measures

Primary Outcomes (2)

• Response rate after induction therapy

  efficacy analysis of anti-CD20 blockade with ofatumumab

  week 9

• rate of MRD-negative patients

  rate of MRD-negative patients who did not experience relapse, progression or death within the first 14 months after study enrollment

  baseline, week 9, month 14

Secondary Outcomes (6)

• Rate of allogeneic HCT

  month 9

• 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

• 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

Study Arms (1)

Ofatumumab

EXPERIMENTAL

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.

Drug: Ofatumumab

Interventions

Ofatumumab DRUG

Study treatment comprises eight weeks of induction therapy with ofatumumab in combination with high-dose dexamethasone. The first dose of ofatumumab is 300 mg followed by seven infusions of 2000 mg ofatumumab. Dexamethasone will be given orally at doses of 40 mg on days 1-4 in weeks 1, 3, 5, and 7. Patients who achieved a CR, PR shall proceed to maintenance therapy. Maintenance therapy consists of 6 monthly infusions of 1000 mg ofatumumab. An HLA-matched sibling donor or HLA-matched unrelated donor can be identified for approximately 70% of patients. Donor search will be completed within six weeks for 95% of the patients. Patients with a donor will proceed to allogeneic HCT as soon as possible prior to, or during maintenance therapy.

Also known as: Arzerra, Anti-CD20 antibody

Ofatumumab

Eligibility Criteria

• Age: 56 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.
• WOCBP includes any female that has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea \>12 consecutive months); or woman on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level \>35mlU/mL.
• WOCBP must have a negative serum or urine pregnancy test prior to the start of the study.

You may not qualify if:

• 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
• 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:
• total bilirubin \>1.5 times upper normal limit (unless due to AIHA or a known history of Gilbert's disease)
• ALT or AST \>2.5 times upper normal limit
• Gamma glutamyl transpeptidase (GGT) \>2.5 times upper normal limit (unless due to disease involvement of the liver)
• Other past or current hematologic or solid organ malignancy. Subjects who have been free of malignancy for at least 3 years, or have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible.
• Male subjects unable or unwilling to use adequate contraception methods from study start to one year after the last dose of protocol therapy.
• Pregnant or lactating woman

Sponsors & Collaborators

• Technische Universität Dresden: lead
• University Hospital Dresden: collaborator
• University Hospital Ulm: collaborator
• University Hospital Schleswig-Holstein: collaborator
• University Hospital of Cologne: collaborator

Study Sites (11)

Universitätsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Universitätsklinikum Ulm

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Städtisches Klinikum München Schwabing

München, Bavaria, 80804, Germany

Location

Klinikum Frankfurt (Oder) GmbH

Frankfurt (Oder), Brandenburg, 15236, Germany

Location

Deutsche Klinik für Diagnostik

Wiesbaden, Hesse, 65191, Germany

Location

Universitätsmedizin Göttingen

Göttingen, Lower Saxony, 37075, Germany

Location

Klinikum der Universität zu Köln

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Universitätsklinikum Düsseldorf

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

Klinikum der Johannes Gutenberg Universität

Mainz, Rhineland-Palatinate, 55131, Germany

Location

Klinikum Chemnitz GmbH

Chemnitz, Saxony, 09113, Germany

Location

Universitätsklinikum Dresden

Dresden, Saxony, 01307, Germany

Location

Related Links

• Website Study Alliance Leukemia (coordinating study group)

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia

Interventions

ofatumumab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Johannes Schetelig, PD Dr. med.

  Universitätsklinikum Carl Gustav Carus, Medizinische Klinik und Poliklinik I, 01307 Dresden

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2012
• First Posted: March 13, 2013
• Study Start: March 1, 2013
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: September 19, 2016

Record last verified: 2016-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (11)