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Chronic Lymphocytic LeukemiaPhase 2CLLTX1NCT03153514

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

A Phase 2 study testing Obinutuzumab in people with Chronic Lymphocytic Leukemia and Richter's Transformation, run by German CLL Study Group at 7 sites in Germany.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Obinutuzumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
7 sitesGermany
Study dates
13 Nov 2017to 6 Jun 2019
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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
  • 18 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

Who cannot join

  • 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
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  • 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
  • Willing to use two methods of reliable contraception including one highly effective (Pearl Index < 1) such as oral hormonal contraceptives, intrauterine device, sexual abstinence and one additional effective (barrier) while on study and maintained for up to 3 years after allogeneic transplantation or 18 months after the last dose of obinutuzumab therapy, whichever is longer
  • Vaccination with a live vaccine a minimum of 28 days prior to randomization
  • Prisoners or patients who are institutionalized by regulatory or court order or persons who are in dependence to the sponsor or an investigator

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

Germany7 sites

  • Universitätsklinikum Bonn

    Bonn, 53105

  • Universitätsklinikum Köln

    Cologne, 50937

  • Universitätsklinikum Essen

    Essen, 45122

  • Universitätsklinikum Heidelberg

    Heidelberg, 69120

  • Universitätsklinikum Leipzig

    Leipzig, 04103

  • Universitätsklinikum Magdeburg

    Magdeburg, 39120

  • Universitätsklinikum München

    München, 81377

Other trials in Germany

About this study

Official title: Obinutuzumab Containing Conditioning Regimen for CLL Patients and Patients With Richter's Transformation Requiring an Allogeneic Stem Cell Transplantation

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.

Read the detailed description

CLL is the most common haematological malignancy in the western world. Though in the majority it behaves like a chronic disease with minimal impact on life expectancy, in around 15-20% of the patients it takes a very aggressive course. Patients who experience a high grade transformation, i.e., Richter's transformation also have a poor prognosis. Despite the advent of new therapeutic agents like Bcl-2 and BTK inhibitors which are revolutionising the outlook for this particular patient cohort, allogeneic stem cell transplantation is the only currently available therapy with the potential to cure. The non relapse mortality associated with this treatment is a major deterrent for physicians and patients alike to opt this intervention. We propose a trial to study the use of a B-cell depleting agent, obinutuzumab to simultaneously reduce tumour bulk control and offer GvHD prophylaxis in the peri-transplant setting and thereby analyse its impact on non relapse morbidity and mortality as well as maximum minimum residual disease (MRD) eradication. All patients with poor risk CLL (current EBMT criteria) and Richter's transformation with the best possible response to available therapies will be considered for the trial. Due to the poor disease control associated with peri-transplant T-cell depletion, obinutuzumab will be used instead of T-cell depleting agents as GvHD prophylaxis.

Being tested
Obinutuzumab
Keywords
CLL
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ObinutuzumabBiological

    Also called GA-101, Gazyva

    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)

Study groups in NCT03153514
Study groupRoleWhat they receive
ObinutuzumabExperimentalObinutuzumab 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
Receives: Biological: Obinutuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. PD-free rate

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

    Measured: 12 months post-transplant

Secondary outcomes (5)

  1. Minimal residual disease (MRD) negativity rate

    Minimal residual disease negativity rate at different time points

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

  2. Overall response rate (ORR)

    The overall response rate (ORR) is defined as the proportion of patients having achieved a CR/CRi, clinical CR/CRi or PR (including PR with lymphocytosis) as best response (according to the IWCLL guidelines (2008)) until and including the response assessment six months after transplantation (=number of patients with best response CR/CRi, clinical CR/CRi or PR (with or without lymphocytosis) divided by the number of the ITT population)

    Measured: 6 months post-transplant

  3. Progression-free survival (PFS)

    Time from the date of enrolment to the date of first occurrence of progression (determined using standard IWCLL guidelines) or death from any cause, whichever occurs first.

    Measured: up to month 24 post-transplant

  4. Event-free survival (EFS)

    Time from the date of enrolment to the date of first occurrence of progression (determined using standard IWCLL guidelines), death from any cause or initiation of subsequent treatment, whichever occurs first.

    Measured: up to month 24 post-transplant

  5. Overall survival (OS)

    Time from the date of enrolment to the date of death due to any cause

    Measured: up to month 24 post-transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 May 2017
  2. Study start13 Nov 2017
  3. Primary completion16 May 2019
  4. Study completion6 Jun 2019

Why it stopped: Prematurely terminated due to poor accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03153514
Sponsor's protocol ID
CLLTX1
Other IDs
2015-000568-32, ML29747, 2015
Acronym
CLLTX1
Status last verified
Oct 2019
First submitted
12 May 2017
Last updated
5 Jan 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Obinutuzumab in people with Chronic Lymphocytic Leukemia and Richter's Transformation, run by German CLL Study Group at 7 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 5 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Prematurely terminated due to poor accrual). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PD-free rate (time frame: 12 months post-transplant). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03153514.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2022.

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