Obinutuzumab Containing Conditioning Regimen for Patients With Poor Risk CLL or Richter's Transformation Requiring Allogeneic Stem Cell Transplantation

NCT03153514 | Terminated Phase 2 DMC

• 3 other identifiers: CLLTX12015-000568-32ML29747
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 7

Brief Summary

The primary objective of the study is to evaluate the feasibility, efficacy and safety of an obinutuzumab containing conditioning regimen for poor risk CLL patients and patients with Richter's transformation requiring an allogeneic stem cell transplantation.

Conditions

Chronic Lymphocytic Leukemia; Richter's Transformation

Keywords

CLL

Outcome Measures

Primary Outcomes (1)

• PD-free rate

  Rate of patients free from disease progression (key efficacy endpoint)

  12 months post-transplant

Secondary Outcomes (5)

• Minimal residual disease (MRD) negativity rate

  days +60, +90, +180, +270 and months 12, 18 and 24 post-transplant

• Overall response rate (ORR)

  6 months post-transplant

• Progression-free survival (PFS)

  up to month 24 post-transplant

• Event-free survival (EFS)

  up to month 24 post-transplant

• Overall survival (OS)

  up to month 24 post-transplant

Study Arms (1)

Obinutuzumab

EXPERIMENTAL

Obinutuzumab i.v. Cycle 1: in the peri-transplant and transplantation phase Cycle 2: if active disease and/or MRD positivity on day +60, +90, +180 or +270

Biological: Obinutuzumab

Interventions

Obinutuzumab BIOLOGICAL

Obinutuzumab i.v. \[Day 0 = day of stem cell transplant\] Cycle 1: 100 mg (d -8), 900 mg (d -7), 1000 mg (d -1, +7, +14) Cycle 2: 1000 mg (d +1, +8, +15, +22)

Also known as: GA-101, Gazyva

Obinutuzumab

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have documented CLL according to iwCLL criteria
• a) CLL requiring transplant according to the consensus statement 2014
• Non-response or early relapse within 24 months after purine analogue combination therapy or treatment of similar efficacy plus high risk CLL TP53 deletion/mutation (del 17p-) and/or del 11 plus response to kinase inhibitors or other small molecules or
• Non-response or early relapse within 24 months after purine analogue combination therapy or treatment of similar efficacy and refractory to or non-tolerating kinase inhibitors or other small molecules or b) Transformation of CLL to aggressive NHL (Richter's transformation) The CLL patients should have at least one therapy with the newer targeted agents such as BCL-2 inhibitors or BCR targeting agents. Both poor risk CLL patients and patients with Richter's transformation should achieve the best possible response defined as disease sensitivity measured as CR, PR or SD prior to transplant with an available salvage therapy
• Availability of a suitable fully matched (10/10) sibling or unrelated donor
• Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 1.
• Hematology values within the following limits unless cytopenia is caused by the underlying disease, i.e., no evidence of additional bone marrow dysfunction (e.g. myelodysplastic syndrome 2, hypoplastic bone marrow):
• Absolute neutrophil count ≥ 1.0 x 109/L
• Platelets ≥ 50 x 109/L and more than 7 days since last transfusion
• Adequate liver function as indicated by a total bilirubin AST, and ALT ≤1.5 the institutional ULN value, unless directly attributable to the patient's CLL
• Negative serological testing for hepatitis B (HBsAg negative and anti-HBc negative, patients positive for anti-HBc may be included if PCR for HBV DNA is negative and HBV-DNA PCR is performed every month until 1 year after last dosage of obinutuzumab), negative testing for hepatitis-C RNA and negative HIV test within 6 weeks prior to registration
• years of age or older but not older then 70 years
• Able and willing to provide written informed consent and to comply with the study protocol procedures
• Patient agrees to inform other physicians about study participation

You may not qualify if:

• Previous allogeneic stem cell transplant
• Known central nervous system (CNS) involvement
• Patients with a history of confirmed PML
• Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (left ventricular ejection fraction \< 50%).
• Organ dysfunction DLCO \< 50%, TLC \< 70%, FEV1 \< 70% and or receiving supplementary oxygen, Inadequate renal function: Creatinine clearance \< 50ml/min
• Patients with active non-controlled infectious disease under treatment (no decrease of CRP or PCT) including active viral infection and active fungal infections with radiological progression despite treatment with Ambisome or active Triazole for more than a month
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies. Known sensitivity or allergy to murine products
• Hypersensitivity to obinutuzumab or to any of the excipients such as for example Mannitol
• Hypersensitivity to Fludarabine or hypersensitivity to both Treosulphan and Busulphan or any of the excipients of the used products
• Hypersensitivity to both Ciclosporin A and calcineurin inhibitors or hypersensitivity to Mycophenolat-Mofetil or any of the excipients of the used products
• Uncontrolled haemolytic anemia
• Participation in another experimental drug trial (including chemotherapy, antibody treatment, kinase inhibitors, BCL2-antagonists or immunmodulatory agents) with start of the conditioning regimen/first obinutuzumab application.
• Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 14 days before start of treatment)
• Fertile men or women of childbearing potential unless:
• Surgically sterile or ≥ 2 years after the onset of menopause

Sponsors & Collaborators

• German CLL Study Group: lead
• Hoffmann-La Roche: collaborator

Study Sites (7)

Universitätsklinikum Bonn

Bonn, 53105, Germany

Location

Universitätsklinikum Köln

Cologne, 50937, Germany

Location

Universitätsklinikum Essen

Essen, 45122, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

Location

Universitätsklinikum Magdeburg

Magdeburg, 39120, Germany

Location

Universitätsklinikum München

München, 81377, Germany

Location

Related Links

• Results of the study

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

obinutuzumab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; 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

• Michael von Bergwelt-Baildon, Prof. Dr. med. Dr. rer. nat.

  University Hospital of Cologne

  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: May 12, 2017
• First Posted: May 15, 2017
• Study Start: November 13, 2017
• Primary Completion: May 16, 2019
• Study Completion: June 6, 2019
• Last Updated: January 5, 2022

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (7)