Leukemia, Lymphocytic, Chronic, B-CellPhase 1NCT01373229
Lenalidomide + Plerixafor in Previously Treated Chronic Lymphocytic Leukemia (CLL)
A Phase 1 study testing Lenalidomide + Plerixafor (+ Rituximab) in people with Leukemia, Lymphocytic, Chronic, B-Cell, run by David Rizzieri, MD at 1 site in United States.
Trial summary
In research studies, lenalidomide (also called Revlimid) has shown some response in chronic lymphocytic leukemia (CLL); however, responses are usually partial responses that occur after several months of taking the study drug. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Lymphocytic, Chronic, B-Cell
- What is being tested?
- Lenalidomide + Plerixafor (+ Rituximab)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2012to Mar 2015
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed diagnosis of chronic lymphocytic leukemia (CLL) or Small lymphocytic lymphoma (SLL) as established by the National Cancer Institute (NCI) Working Group Response Criteria (NCI 96 Criteria).
- Received one or more prior therapies for CLL.
- Subjects must have symptomatic disease requiring therapy as defined by the protocol.
- >/= 4 weeks from prior cancer therapy.
- Eastern Cooperative Oncology Group (ECOG) performance status of </= 2.
- All study subjects must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
Who cannot join
- Prolymphocytic leukemia (PLL).
- Richter's (large cell) transformation.
- Prior allogeneic transplant within 12 months or prior allogeneic transplant > 12 months currently receiving immunosuppressants.
- Active autoimmune hemolytic anemia.
- Central nervous system (CNS) involvement.
- Chronic enteral corticosteroids > 10mg prednisone or equivalent.
Show all 13Show fewer
- Evidence of laboratory tumor lysis syndrome (TLS) by Cairo-Bishop Definition of Tumor Lysis Syndrome
- Use of any other experimental drug or therapy within 28 days of baseline
- Major surgery within 28 days of baseline.
- Known hypersensitivity to thalidomide.
- The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
- Any prior use of lenalidomide.
- Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV).
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: Lenalidomide in Combination With Plerixafor in Patients With Previously Treated Chronic Lymphocytic Leukemia
In research studies, lenalidomide (also called Revlimid) has shown some response in chronic lymphocytic leukemia (CLL); however, responses are usually partial responses that occur after several months of taking the study drug. It is thought that by adding the drug plerixafor (also called Mozobil) responses may be improved and/or occur sooner.
The main purpose of this study is to determine the dose of plerixafor that is safe to use in combination with lenalidomide. The study will also look at the response rates of the combination of lenalidomide and plerixafor and the effect the study drugs have on CLL cells.
Read the detailed description
The combination of lenalidomide and plerixafor will be evaluated in this single institution, open label clinical study of subjects with relapsed chronic lymphocytic leukemia (CLL). The overall design of the phase 1 study includes up to three treatment "stages."
Each subject will receive lenalidomide 5mg by mouth daily beginning on cycle 1 day 1. If tolerated, the dose will be increased by 2.5mg every 7 days to a maximum dose of 10mg by mouth daily (Stage 1). Once the subject is stably maintained on a daily dose of lenalidomide of 10mg daily and the white blood cell (WBC) count is <100.0 x 109 / L, and has been taking lenalidomide for at least 28 days, plerixafor will be added (Stage 2). In the dose escalation phase, 4 different doses of plerixafor in combination with lenalidomide will be studied in cohorts of 3 to 6 subjects each, following a standard "3 + 3" format:
- Cohort 1: plerixafor 0.24 mg/kg subcutaneous (SC) daily thrice weekly (Mon, Wed, Fri)
- Cohort 2: plerixafor 0.32 mg/kg SC daily thrice weekly (Mon, Wed, Fri)
- Cohort 3: plerixafor 0.42 mg/kg SC daily thrice weekly (Mon, Wed, Fri)
- Cohort 4: plerixafor 0.54 mg/kg SC daily thrice weekly (Mon, Wed, Fri) Plerixafor will be administered for 3 weeks of each cycle (days 1, 3, 5, 8, 10, 12, 15, 17, and 19) followed by a 1 week rest period. Lenalidomide dosing will be continuous.
An interim assessment of response will be performed after 4 cycles of combination therapy:
- Subjects achieving a complete response (CR) by National Cancer Institute (NCI)-96 criteria will continue lenalidomide monotherapy (plerixafor is discontinued) until disease progression.
- Subjects achieving a partial response (PR) will continue both lenalidomide and plerixafor. Additionally, rituximab 375mg/m2 will be added on day 1 of each subsequent cycle beginning with cycle 5, day 1 of combination therapy. (Stage 3). Treatment with the combination of lenalidomide and plerixafor will continue for a maximum of 12 cycles of combination therapy. Subjects may receive up to 8 doses of rituximab concurrent with lenalidomide and plerixafor on day 1 of each cycle. Subjects will then continue single agent lenalidomide until disease progression.
- Subjects with stable disease may continue lenalidomide and plerixafor at the discretion of the investigator and the subject. Rituximab 375 mg/m2 will be added on day 1 of each subsequent cycle. Treatment, dose, schedule, and duration are the same as for subjects achieving a PR.
- Conditions
- Leukemia, Lymphocytic, Chronic, B-Cell
- Being tested
- Lenalidomide + Plerixafor (+ Rituximab)
- Keywords
- Chronic Lymphocytic Leukemia, 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.
Lenalidomide + Plerixafor (+ Rituximab)Drug
Also called Revlimid, Mozobil, Rituxan
- Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1.
- Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg.
- Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) <100.0 x 109 / L.
- Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide:
- Cohort 1: 0.24 mg/kg
- Cohort 2: 0.32 mg/kg
- Cohort 3: 0.42 mg/kg
- Cohort 4: 0.54 mg/kg
- Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR.
- Subjects will then continue single agent lenalidomide until disease progression.
| Study group | Role | What they receive |
|---|---|---|
| Lenalidomide + Plerixafor+ Rituximab | Experimental | 1. Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1.
2. Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg.
3. Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) <100.0 x 109 / L.
4. Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide:
* Cohort 1: 0.24 mg/kg
* Cohort 2: 0.32 mg/kg
* Cohort 3: 0.42 mg/kg
* Cohort 4: 0.54 mg/kg
5. Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR.
6. Subjects will then continue single agent lenalidomide until disease progression. Receives: Drug: Lenalidomide + Plerixafor (+ Rituximab) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose
Measured: 4-16 months
Secondary outcomes (5)
Overall Response (Complete Response/Partial Response)
NCI 96 Response Criteria
CR (Complete Response):
Lymphadenopathy = none > 1.5cm Hepatomegaly = none Splenomegaly = none Blood lymphocytes = <4000 per microliter Marrow = normocellular, <30% lymphocytes, no B-lymphoid nodules. Platelet count = >100,000 per microliter Hemoglobin = >11.0 grams per deciliter Neutrophils = >1500 per microliter
PR (Partial Response):
Lymphadenopathy = Decrease >/= 50% Hepatomegaly = Decrease >/= 50% Splenomegaly = Decrease >/= 50% Blood lymphocytes = Decrease >/= 50% from baseline Marrow = 50% reduction in marrow infiltrate or B-lymphoid nodules. Platelet count = >100,000 per microliter or increase >/= 50% over baseline Hemoglobin = >11.0 grams per deciliter or increase >/= 50% over baseline Neutrophils = >1500 per microliter or increase >/= 50% over baseline
Measured: at the end of 4 months of combination treatment and at 2 months after completion of therapy
Progression-free Survival (PFS)
Measured: time from day 1 of treatment to disease progression, death, or 2 years, whichever comes first
Overall Survival (OS)
Measured: the time from day 1 of treatment to death or 2 years, whichever comes first
Reduction in Severity of B Symptoms
Reduction in the severity of the following B symptoms will be assessed: fever ≥ 101F, chills, night sweats, and anorexia with weight loss.
Measured: at the end of stage 1 (lenalidomide alone), at the end of stage 2 (4 months of combination), and at 2 months post-completion of therapy
Reduction in the Frequency of Blood and Platelet Transfusions
The change in number of transfusions from pre- to post-treatment will be calculated and summarized across all patients by giving the minimum, the 25th, 50th (median) and the 75th percentile and the maximum.
Measured: 4 weeks prior to therapy and in the 4 weeks following the completion of therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2011 (estimated)
- Study startJan 2012
- Primary completionMar 2014
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Leukemia, Lymphocytic, Chronic, B-CellStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- David Rizzieri, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Celgene Corporation, Genzyme, a Sanofi Company
- Responsible party
- Sponsor-investigator, David Rizzieri, MD, Duke University
- Investigators
- David A Rizzieri, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01373229
- Sponsor's protocol ID
- Pro00026715
- Other IDs
- RV0622
- Status last verified
- Jul 2017
- First submitted
- 12 Jun 2011
- Last updated
- 5 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lenalidomide in Combination With Plerixafor in Patients With Previously Treated Chronic Lymphocytic Leukemia
- ClinicalTrials.gov ID
- NCT01373229
- Acronym / sponsor ID
- Pro00026715
- Conditions
- Leukemia, Lymphocytic, Chronic, B-Cell
- Keywords
- Chronic Lymphocytic Leukemia, CLL
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- David Rizzieri, MDUniversity, hospital or other
- Collaborators
- Celgene Corporation, Genzyme, a Sanofi Company
- Study start
- Jan 2012 (actual)
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 14 Jun 2011 (estimated)
- Results
- Posted 5 Feb 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In research studies, lenalidomide (also called Revlimid) has shown some response in chronic lymphocytic leukemia (CLL); however, responses are usually partial responses that occur after several months of taking the study drug. It is thought that by adding the drug plerixafor (also called Mozobil) responses may be improved and/or occur sooner.
The main purpose of this study is to determine the dose of plerixafor that is safe to use in combination with lenalidomide. The study will also look at the response rates of the combination of lenalidomide and plerixafor and the effect the study drugs have on CLL cells.
Detailed description
The combination of lenalidomide and plerixafor will be evaluated in this single institution, open label clinical study of subjects with relapsed chronic lymphocytic leukemia (CLL). The overall design of the phase 1 study includes up to three treatment "stages."
Each subject will receive lenalidomide 5mg by mouth daily beginning on cycle 1 day 1. If tolerated, the dose will be increased by 2.5mg every 7 days to a maximum dose of 10mg by mouth daily (Stage 1). Once the subject is stably maintained on a daily dose of lenalidomide of 10mg daily and the white blood cell (WBC) count is <100.0 x 109 / L, and has been taking lenalidomide for at least 28 days, plerixafor will be added (Stage 2). In the dose escalation phase, 4 different doses of plerixafor in combination with lenalidomide will be studied in cohorts of 3 to 6 subjects each, following a standard "3 + 3" format:
- Cohort 1: plerixafor 0.24 mg/kg subcutaneous (SC) daily thrice weekly (Mon, Wed, Fri)
- Cohort 2: plerixafor 0.32 mg/kg SC daily thrice weekly (Mon, Wed, Fri)
- Cohort 3: plerixafor 0.42 mg/kg SC daily thrice weekly (Mon, Wed, Fri)
- Cohort 4: plerixafor 0.54 mg/kg SC daily thrice weekly (Mon, Wed, Fri) Plerixafor will be administered for 3 weeks of each cycle (days 1, 3, 5, 8, 10, 12, 15, 17, and 19) followed by a 1 week rest period. Lenalidomide dosing will be continuous.
An interim assessment of response will be performed after 4 cycles of combination therapy:
- Subjects achieving a complete response (CR) by National Cancer Institute (NCI)-96 criteria will continue lenalidomide monotherapy (plerixafor is discontinued) until disease progression.
- Subjects achieving a partial response (PR) will continue both lenalidomide and plerixafor. Additionally, rituximab 375mg/m2 will be added on day 1 of each subsequent cycle beginning with cycle 5, day 1 of combination therapy. (Stage 3). Treatment with the combination of lenalidomide and plerixafor will continue for a maximum of 12 cycles of combination therapy. Subjects may receive up to 8 doses of rituximab concurrent with lenalidomide and plerixafor on day 1 of each cycle. Subjects will then continue single agent lenalidomide until disease progression.
- Subjects with stable disease may continue lenalidomide and plerixafor at the discretion of the investigator and the subject. Rituximab 375 mg/m2 will be added on day 1 of each subsequent cycle. Treatment, dose, schedule, and duration are the same as for subjects achieving a PR.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lenalidomide + Plerixafor+ Rituximab | Experimental | Drug: Lenalidomide + Plerixafor (+ Rituximab)1. Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1. 2. Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg. 3. Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) <100.0 x 109 / L. 4. Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide: * Cohort 1: 0.24 mg/kg * Cohort 2: 0.32 mg/kg * Cohort 3: 0.42 mg/kg * Cohort 4: 0.54 mg/kg 5. Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR. 6. Subjects will then continue single agent lenalidomide until disease progression. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Histologically confirmed diagnosis of chronic lymphocytic leukemia (CLL) or Small lymphocytic lymphoma (SLL) as established by the National Cancer Institute (NCI) Working Group Response Criteria (NCI 96 Criteria).
- Received one or more prior therapies for CLL.
- Subjects must have symptomatic disease requiring therapy as defined by the protocol.
- >/= 4 weeks from prior cancer therapy.
- Eastern Cooperative Oncology Group (ECOG) performance status of </= 2.
Key exclusion criteria (13 listed)
- Prolymphocytic leukemia (PLL).
- Richter's (large cell) transformation.
- Prior allogeneic transplant within 12 months or prior allogeneic transplant > 12 months currently receiving immunosuppressants.
- Active autoimmune hemolytic anemia.
- Central nervous system (CNS) involvement.
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 |
|---|---|---|
| Lenalidomide + Plerixafor (+ Rituximab)Also: Revlimid, Mozobil, Rituxan1. Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1. 2. Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg. 3. Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) <100.0 x 109 / L. 4. Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide: * Cohort 1: 0.24 mg/kg * Cohort 2: 0.32 mg/kg * Cohort 3: 0.42 mg/kg * Cohort 4: 0.54 mg/kg 5. Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR. 6. Subjects will then continue single agent lenalidomide until disease progression. | Drug | Lenalidomide + Plerixafor+ Rituximab |
Primary outcome
Maximum Tolerated Dose
Time frame: 4-16 months
5 secondary outcomes
Overall Response (Complete Response/Partial Response)
Time frame: at the end of 4 months of combination treatment and at 2 months after completion of therapy
Progression-free Survival (PFS)
Time frame: time from day 1 of treatment to disease progression, death, or 2 years, whichever comes first
Overall Survival (OS)
Time frame: the time from day 1 of treatment to death or 2 years, whichever comes first
Reduction in Severity of B Symptoms
Time frame: at the end of stage 1 (lenalidomide alone), at the end of stage 2 (4 months of combination), and at 2 months post-completion of therapy
Reduction in the Frequency of Blood and Platelet Transfusions
Time frame: 4 weeks prior to therapy and in the 4 weeks following the completion of therapy
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
David A Rizzieri, MD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lenalidomide + Plerixafor (+ Rituximab) in people with Leukemia, Lymphocytic, Chronic, B-Cell, run by David Rizzieri, MD at 1 site in United States.
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 6 inclusion and 13 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 5 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Feb 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Maximum Tolerated Dose (time frame: 4-16 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Feb 2018.