Chronic Lymphocytic LeukemiaPhase 2NCT01455051
Ofatumumab as Part of Reduced Intensity Conditioning (RIC) Regimen for Patients With High Risk Chronic Lymphocytic Leukemia (CLL) Undergoing Allogeneic Hematopoietic Cell Transplantation
A Phase 2 study testing Ofatumumab in people with Chronic Lymphocytic Leukemia, run by Grupo Espanol de trasplantes hematopoyeticos y terapia celular at 9 sites in Spain.
Trial summary
A good proportion of patients with chronic lymphocytic leukemia (CLL) can be managed effectively with palliative chemotherapy. However, there is a group of younger patients with poor risk disease whose life expectancy is significantly reduced. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Chronic Lymphocytic Leukemia
- What is being tested?
- Ofatumumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 9 sitesSpain
- Study dates
- Oct 2011to Oct 2017
- 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
- Patients diagnosed with CD20+ chronic lymphocytic leukemia according to the World Health Organization.
- Patients older than 18 and younger than 70 years old.
- Patients who failed to meet NCI Working Group criteria for complete or partial response after therapy with regimens containing fludarabine or with disease relapse within 12 months after completing therapy with fludarabine containing regimen. Patients not eligible for fludarabine treatment, could also be included provided the disease remains unresponsive or relapses with 12 months after completing alternative salvage regimens (i.e. autologous HCT, bendamustine, gemcitabine, alemtuzumab or high-dose methyl-prednisolone), OR Patients with novo or acquired "17p deletion" cytogenetic abnormality. These patients must have received induction chemotherapy but could be transplanted in first complete or partial response.
- Patients must have achieved a complete or partial response after the last therapy given prior to transplantation. Patients with clinically suspected or histologically confirmed Richter's transformation could be included if they are in complete response at the time of transplantation.
- Patients who have not received more than four lines of therapy prior to transplantation.
- Patients who have suitable HLA-matched related or unrelated donors willing to receive G-CSF, undergo apheresis to collect PBMC, and to donate stem cells. Patients with a single-locus mismatched donor available are also eligible.
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- ECOG functional status of 0 to 2.
- Life expectancy of at least 6 months.
- Signed informed consent.
Who cannot join
- Intolerance to rituximab or any other anti-CD20 monoclonal antibody.
- Diagnosis of CNS involvement with CLL.
- Prior allogeneic HCT.
- Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).
- 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 currently participating in any other interventional clinical study.
- Other past or current malignancy. Subjects who have been free of malignancy for at least 5 years, or have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible.
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- Active infection unresponsive to medical therapy such as, but not limited to, chronic renal infection, chronic chest infection, tuberculosis and active hepatitis C.
- History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae.
- Known HIV positive.
- Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (NYHA III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities.
- Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the patient.
- Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded.
- Positive serology for hepatitis C (HC) defined as a positive test for HCAb, in which case reflexively perform a HC RIBA immunoblot assay on the same sample to confirm the result.
- Severe organ dysfunction as defined by: cardiac ejection fraction <40%; DLCO <40%; calculated GFR < 30 ml/min; or bilirubin > 3 times the upper normal limit (unless due to CLL or Gilbert syndrome).
- Pregnant or lactating women. Women of childbearing potential must have a negative pregnancy test at screening.
- Women of childbearing potential, including women whose last menstrual period was less than one year prior to screening, unable or unwilling to use adequate contraception from study start to one year after the last dose of protocol therapy. Adequate contraception is defined as hormonal birth control, intrauterine device, double barrier method or total abstinence.
- Male subjects unable or unwilling to use adequate contraception methods from study start to one year after the last dose of protocol therapy.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
Spain9 sites
Hospital Germans Trias i Pujol
Badalona
Hospital de la Santa Creu Sant Pau
Barcelona, 08025
Hospital Vall d'Hebron
Barcelona
Institut Catala d'Oncologia
L'Hospitalet de Llobregat
Hospital La Princesa
Madrid
Hospital Puerta de Hierro
Madrid
Hospital Central de Asturias
Oviedo
Hospital Clinico
Valencia
Hospital La Fe
Valencia
About this study
Official title: Ofatumumab as Part of the Reduced Intensity Conditioning Regimen for Patients With High Risk Chronic Lymphocytic Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation: a Pilot Study by GETH and GELLC
A good proportion of patients with chronic lymphocytic leukemia (CLL) can be managed effectively with palliative chemotherapy. However, there is a group of younger patients with poor risk disease whose life expectancy is significantly reduced. As a result, reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (allo-HCT) has been investigated as a potentially curative procedure.
Recently, the European Group for Blood and Marrow Transplantation (EBMT) published a set of guidelines suggesting situations where allo-HCT might be considered a therapeutic option for CLL patients. Their conclusions were that allo-HCT was reasonable for younger CLL patients refractory to fludarabine, relapsing within two years of intensive treatment, or with p53 abnormalities requiring treatment.
Read more
However, the results with RIC allo-HCT are not entirely satisfactory, and progression-free survival after allo-HCT revolves around 35-40% at 3-5 years following allo-HCT. This is due to non-relapse mortality, which is significantly associated with the development of graft-versus-host disease (GVHD), but also due to disease relapse. These relapses may occur early in the course of the transplantation, like any other hematological malignancy, but late relapses have also been reported.
Several strategies have been tested in order to improve these results. The anti-CD20 monoclonal antibody rituximab, given concomitantly with allo-HCT or donor lymphocyte infusions, may reduce graft-versus-host disease and facilitate disease control. This may be due, not only to direct cytotoxicity, but also to modulation of GVHD and the graft-versus CLL effect (GVCLL). Interestingly, rituximab has been shown to promote the cross-presentation of tumor-derived peptides by antigen-presenting cells, thus enhancing the formation of cytotoxic T-cell clones and a GVCLL effect. With the addition of rituximab to the conditioning regimen, rates at 4 years for current progression-free survival (CPFS) and overall survival were 44% and 48%.
The investigators hypothesize that ofatumumab, having a more potent anti-CLL activity and complement-dependent cytoxicity than rituximab, could improve disease control and modulate the GVCLL effect more effectively, thus reducing the GVHD rate and subsequently improving the non-relapse mortality and progression-free survival in the long term.
- Conditions
- Chronic Lymphocytic Leukemia
- Being tested
- Ofatumumab
- 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.
OfatumumabDrug
Also called Arzerra
We plan to add five doses of ofatumumab to the standard conditioning regimen (fludarabine + melphalan). Ofatumumab will be administered on days -20 (300 mg), -13 (2000 mg), -6 (2000 mg), +1 (1000 mg) and +8 (1000 mg) of the transplantation (day 0 being the day of the hematopoietic cell infusion). If the patient requires donor lymphocyte infusions within 3 years after the procedure, these infusions will also include one administration of 300 mg of ofatumumab, followed by a 1000 mg dose, 7 days later).
| Study group | Role | What they receive |
|---|---|---|
| Ofatumumab | Experimental | We plan to add five doses of ofatumumab to the standard conditioning regimen (fludarabine + melphalan). Ofatumumab will be administered on days -20 (300 mg), -13 (2000 mg), -6 (2000 mg), +1 (1000 mg) and +8 (1000 mg) of the transplantation (day 0 being the day of the hematopoietic cell infusion). If the patient requires donor lymphocyte infusions within 3 years after the procedure, these infusions will also include one administration of 300 mg of ofatumumab, followed by a 1000 mg dose, 7 days later). Receives: Drug: Ofatumumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
CPFS at 3y
Current progression-free survival (CPFS) at 3 years.
Measured: At 3 years
Secondary outcomes (6)
CPFS at 5y
Current progression-free survival (CPFS) at 5 years
Measured: At 5 years
NRM at 1/5 years
Non-relapse mortality at 1 and 5 years
Measured: At 1 and 5 years
Acute GVHD at 3mo
Incidence of acute graft-versus-host disease, grade II-IV, at 3 months
Measured: At 3 months
Chronic GVHD at 1/5y
Incidence of extensive chronic graft-versus-host disease at 1 and 5 years
Measured: At 1 and 5 years
Toxicity criteria
Evaluation of toxicity following common toxicity criteria, release 3.0
Measured: During all 3 years
OS at 3/5y
Overall survival at 3 and 5 years
Measured: At 3 and 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2011 (estimated)
- Study startOct 2011
- Primary completionOct 2014
- Study completionOct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grupo Espanol de trasplantes hematopoyeticos y terapia celular
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Julio Delgado, MD, PhD, Principal investigator, Hospital Clinic of Barcelona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01455051
- Sponsor's protocol ID
- GETH-CLL4
- Other IDs
- 2010-024467-40
- Status last verified
- May 2022
- First submitted
- 17 Oct 2011
- Last updated
- 6 May 2022
- Results posted
- No
- Data monitoring committee
- No
Publications
Montesinos P, Cabrero M, Valcarcel D, Rovira M, Garcia-Marco JA, Loscertales J, Moreno C, Duarte R, Terol MJ, Villamor N, Abrisqueta P, Caballero D, Sanz J, Delgado J. The addition of ofatumumab to the conditioning regimen does not improve the outcome of patients with high-risk CLL undergoing reduced intensity allogeneic haematopoietic cell transplantation: a pilot trial from the GETH and GELLC (CLL4 trial). Bone Marrow Transplant. 2016 Oct;51(10):1404-1407. doi: 10.1038/bmt.2016.145. Epub 2016 May 23. No abstract available.
PubMed 27214073
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ofatumumab as Part of the Reduced Intensity Conditioning Regimen for Patients With High Risk Chronic Lymphocytic Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation: a Pilot Study by GETH and GELLC
- ClinicalTrials.gov ID
- NCT01455051
- Acronym / sponsor ID
- GETH-CLL4
- Conditions
- Chronic Lymphocytic Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Grupo Espanol de trasplantes hematopoyeticos y terapia celularUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- Oct 2011
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2017 (actual)
- First posted
- 19 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A good proportion of patients with chronic lymphocytic leukemia (CLL) can be managed effectively with palliative chemotherapy. However, there is a group of younger patients with poor risk disease whose life expectancy is significantly reduced. As a result, reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (allo-HCT) has been investigated as a potentially curative procedure.
Recently, the European Group for Blood and Marrow Transplantation (EBMT) published a set of guidelines suggesting situations where allo-HCT might be considered a therapeutic option for CLL patients. Their conclusions were that allo-HCT was reasonable for younger CLL patients refractory to fludarabine, relapsing within two years of intensive treatment, or with p53 abnormalities requiring treatment.
However, the results with RIC allo-HCT are not entirely satisfactory, and progression-free survival after allo-HCT revolves around 35-40% at 3-5 years following allo-HCT. This is due to non-relapse mortality, which is significantly associated with the development of graft-versus-host disease (GVHD), but also due to disease relapse. These relapses may occur early in the course of the transplantation, like any other hematological malignancy, but late relapses have also been reported.
Several strategies have been tested in order to improve these results. The anti-CD20 monoclonal antibody rituximab, given concomitantly with allo-HCT or donor lymphocyte infusions, may reduce graft-versus-host disease and facilitate disease control. This may be due, not only to direct cytotoxicity, but also to modulation of GVHD and the graft-versus CLL effect (GVCLL). Interestingly, rituximab has been shown to promote the cross-presentation of tumor-derived peptides by antigen-presenting cells, thus enhancing the formation of cytotoxic T-cell clones and a GVCLL effect. With the addition of rituximab to the conditioning regimen, rates at 4 years for current progression-free survival (CPFS) and overall survival were 44% and 48%.
The investigators hypothesize that ofatumumab, having a more potent anti-CLL activity and complement-dependent cytoxicity than rituximab, could improve disease control and modulate the GVCLL effect more effectively, thus reducing the GVHD rate and subsequently improving the non-relapse mortality and progression-free survival in the long term.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ofatumumab | Experimental | Drug: OfatumumabWe plan to add five doses of ofatumumab to the standard conditioning regimen (fludarabine + melphalan). Ofatumumab will be administered on days -20 (300 mg), -13 (2000 mg), -6 (2000 mg), +1 (1000 mg) and +8 (1000 mg) of the transplantation (day 0 being the day of the hematopoietic cell infusion). If the patient requires donor lymphocyte infusions within 3 years after the procedure, these infusions will also include one administration of 300 mg of ofatumumab, followed by a 1000 mg dose, 7 days later). |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients diagnosed with CD20+ chronic lymphocytic leukemia according to the World Health Organization.
- Patients older than 18 and younger than 70 years old.
- Patients who failed to meet NCI Working Group criteria for complete or partial response after therapy with regimens containing fludarabine or with disease relapse within 12 months after completing therapy with fludarabine containing regimen. Patients not eligible for fludarabine treatment, could also be included provided the disease remains unresponsive or relapses with 12 months after completing alternative salvage regimens (i.e. autologous HCT, bendamustine, gemcitabine, alemtuzumab or high-dose methyl-prednisolone), OR Patients with novo or acquired "17p deletion" cytogenetic abnormality. These patients must have received induction chemotherapy but could be transplanted in first complete or partial response.
- Patients must have achieved a complete or partial response after the last therapy given prior to transplantation. Patients with clinically suspected or histologically confirmed Richter's transformation could be included if they are in complete response at the time of transplantation.
- Patients who have not received more than four lines of therapy prior to transplantation.
Key exclusion criteria (17 listed)
- Intolerance to rituximab or any other anti-CD20 monoclonal antibody.
- Diagnosis of CNS involvement with CLL.
- Prior allogeneic HCT.
- Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).
- 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 currently participating in any other interventional clinical study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OfatumumabAlso: ArzerraWe plan to add five doses of ofatumumab to the standard conditioning regimen (fludarabine + melphalan). Ofatumumab will be administered on days -20 (300 mg), -13 (2000 mg), -6 (2000 mg), +1 (1000 mg) and +8 (1000 mg) of the transplantation (day 0 being the day of the hematopoietic cell infusion). If the patient requires donor lymphocyte infusions within 3 years after the procedure, these infusions will also include one administration of 300 mg of ofatumumab, followed by a 1000 mg dose, 7 days later). | Drug | Ofatumumab |
Primary outcome
CPFS at 3y
Time frame: At 3 years
Current progression-free survival (CPFS) at 3 years.
6 secondary outcomes
CPFS at 5y
Time frame: At 5 years
NRM at 1/5 years
Time frame: At 1 and 5 years
Acute GVHD at 3mo
Time frame: At 3 months
Chronic GVHD at 1/5y
Time frame: At 1 and 5 years
Toxicity criteria
Time frame: During all 3 years
OS at 3/5y
Time frame: At 3 and 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2022.
- Results publication: PubMed 27214073Montesinos P, Cabrero M, Valcarcel D, Rovira M, Garcia-Marco JA, Loscertales J, Moreno C, Duarte R, Terol MJ, Villamor N, Abrisqueta P, Caballero D, Sanz J, Delgado J. The addition of ofatumumab to the conditioning regimen does not improve the outcome of patients with high-risk CLL undergoing reduced intensity allogeneic haematopoietic cell transplantation: a pilot trial from the GETH and GELLC (CLL4 trial). Bone Marrow Transplant. 2016 Oct;51(10):1404-1407. doi: 10.1038/bmt.2016.145. Epub 2016 May 23. No abstract available.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julio Delgado, MD, PhD principal investigator
Hospital Clinic of Barcelona
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ofatumumab in people with Chronic Lymphocytic Leukemia, run by Grupo Espanol de trasplantes hematopoyeticos y terapia celular at 9 sites in Spain.
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 9 inclusion and 17 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: finished, as of the sponsor's last update on 6 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Spain. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
CPFS at 3y (time frame: At 3 years). 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 NCT01455051, which also lists 1 linked publication.
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 6 May 2022; AzTrials last refreshed its copy on 8 Nov 2026.