Chronic Lymphocytic LeukemiaPhase 2NCT01173679
Dasatinib With Fludarabine and Rituximab in Relapsed and Refractory CLL and SLL
A Phase 2 study testing dasatinib, Rituximab and fludarabine in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Massachusetts General Hospital at 3 sites in United States.
Trial summary
Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL) are similar diseases of the white blood cells and are typically treated the same way. Recent research shows that a key enzyme in CLL cells is responsible for cell survival. This enzyme is called LYN kinase. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
- What is being tested?
- dasatinib, Rituximab and fludarabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 3 sitesUnited States
- Study dates
- Jul 2010to Jan 2015
- Phase
- Phase 2
- 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
- CLL/SLL with cells positive by flow cytometry (or immunostaining) for CD19, CD23, and CD5. Patients may be CD23 negative as long as they are also cyclin D1 negative or t(11;14) negative.
- Participants must have received at least 1 prior regimen containing a purine analogue or have received at least 2 chemotherapy regimens not containing a purine analogue. Patients may be refractory to single-agent purine analogue treatment, but patients may not be refractory to a combination of purine analogue with rituximab. Patients may have received rituximab.
- 18 years of age or older
- Able to take oral medications
- ECOG Performance Status of 2 or better
- Adequate organ function to tolerate chemotherapy
Show all 10Show fewer
- Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the start of study drug administration and agree to use and utilize an adequate method of contraception throughout treatment and for at least 4 weeks after study is stopped.
- Require treatment based on 1996 NCI-WG criteria updated in 2008 by the IWCLL
- Patient agrees to discontinue St. John's Wort while receiving dasatinib therapy and stop at least 5 days before starting dasatinib.
- Patient agrees that IV bisphosphonates will be withheld for the first 8 weeks of dasatinib
Who cannot join
- Pregnant or breastfeeding women
- Uncontrolled angina, congestive heart failure, or MI within 6 months
- Diagnosed or suspected congenital long QT syndrome
- Any history of clinically significant ventricular arrhythmias
- Prolonged QTc interval on pre-entry ECG
- Uncontrolled hypertension
Show all 12Show fewer
- Hypokalemia or hypomagnesemia that is not corrected prior to dasatinib administration
- Patients should not be taking drugs that are generally accepted to have a risk of causing Torsades de Pointes
- Known HIV positive
- Known significant bleeding disorder unrelated to CLL
- Any significant pleural or pericardial effusion
- Patients may not have another malignancy that is uncontrolled or requires treatment within a year of starting this study.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
Official title: Phase II Trial of Dasatinib With Fludarabine and Rituximab in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL) are similar diseases of the white blood cells and are typically treated the same way. Recent research shows that a key enzyme in CLL cells is responsible for cell survival. This enzyme is called LYN kinase. Laboratory studies show that inhibition of LYN kinase in CLL cells results in the death of CLL cells. Dasatinib has the ability to inhibit LYN kinase and, therefore, should have some effect on CLL cells. The purpose of this study is to see of the study drug dasatinib, in combination with fludarabine and rituximab, is safe and effective to use for people with relapsed or refractory CLL/SLL.
Read the detailed description
- Since the purpose of the study is to determine the response rate of the 3 drug regimen, everyone who participates will receive the same dose of the study drug, dasatinib and the 2 standard drugs, fludarabine and rituximab.
- Participants will receive the drugs dasatinib, fludarabine, and rituximab at the following time points through each cycle of treatment. A cycle of study treatment is 28 days. Dasatinib pills will be taken orally each day for the first 2 weeks of each cycle. Fludarabine will be give intravenously on three days of each cycle (Days 3-5 in the first cycle, days 1-3 after that). Rituximab will be given intravenously with a total dose of 375 mg/m2 each cycle (split on Days 3+4 in the first cycle and at the discretion of the treating physician after that on Days 1-3).
- The following procedures will be repeated throughout the study: medical history review; physical exam; performance status test; blood tests and EKG. They will occur daily during the first week of treatment, then weekly for the rest of cycle 1. After cycle 1 these procedures will be done once a week for 4 weeks then once a month for 6 months.
- Tumor assessments will be repeated once every 2 months for the first six months of the study, and then once every 6 months after that.
- Blood samples will be obtained in the first 5 days of treatment for pharmacokinetic studies and pharmacodynamic studies.
- Participants that are benefiting from the study treatment after the first cycle can continue to receive an additional 6 cycles of study treatment.
- Being tested
- dasatinib, Rituximab, fludarabine
- Keywords
- CLL, fludarabine, rituximab, dasatinib, refractory, relapsed
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dasatinibDrug
Taken orally once a day on days 1-14 of each 28-day cycle
RituximabDrug
Given intravenously, 375 mg/m2 each cycle (dose split, given on Days 3+4 of cycle 1, variable after that).
fludarabineDrug
Given intravenously, 25 mg/m2/day, for 3 doses per cycle (Days 3-5 in cycle 1, Days 1-3 after that)
| Study group | Role | What they receive |
|---|---|---|
| dasatinib, rituximab, fludarabine | Other | Single-arm, open-label Receives: Drug: dasatinib; Drug: Rituximab; Drug: fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate
To describe the response rate of complete response (CR) and partial response (PR) to treatment with this drug combination (SD=stable disease, PD=progressive disease)
Measured: 2 years
Secondary outcomes (2)
Progression-Free and Overall Survival
To describe the progression-free and overall surivial
Measured: 2 years
Toxicities
Dasatinib may enhance the myelosuppression expected from fludarabine. This toxicity will be monitored with frequent CBC's. If after Day 21 of a cycle there is a grade 4 cytopenia, a dose reduction will occur in the next cycle of treatment, and that cycle cannot start until the ANC > 1,000 and the platelets > 25,000. There is also a risk for pleural effusions with dasatinib, but the risk will be low, since there is a break from dasatinib dosing on days 15-28 of each cycle. Nevertheless, if a grade 2 pleural effusion occurs, there will be a dose reduction in the next cycle of treatment.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2010 (estimated)
- Study startJul 2010
- Primary completionJan 2015
- Study completionJan 2015
Why it stopped: Slow accrual
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 Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- 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
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, Bristol-Myers Squibb
- Responsible party
- Principal investigator, Philip C. Amrein, M.D., Massachusetts General Hospital
- Investigators
- Philip Amrein, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01173679
- Sponsor's protocol ID
- 09-325
- Status last verified
- Mar 2017
- First submitted
- 28 Jul 2010
- Last updated
- 14 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: I do not plan to share IPD.
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Dasatinib With Fludarabine and Rituximab in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma
- ClinicalTrials.gov ID
- NCT01173679
- Acronym / sponsor ID
- 09-325
- Keywords
- CLL, fludarabine, rituximab, dasatinib, refractory, relapsed
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, Bristol-Myers Squibb
- Study start
- Jul 2010
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 2 Aug 2010 (estimated)
- Results
- Posted 20 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL) are similar diseases of the white blood cells and are typically treated the same way. Recent research shows that a key enzyme in CLL cells is responsible for cell survival. This enzyme is called LYN kinase. Laboratory studies show that inhibition of LYN kinase in CLL cells results in the death of CLL cells. Dasatinib has the ability to inhibit LYN kinase and, therefore, should have some effect on CLL cells. The purpose of this study is to see of the study drug dasatinib, in combination with fludarabine and rituximab, is safe and effective to use for people with relapsed or refractory CLL/SLL.
Detailed description
- Since the purpose of the study is to determine the response rate of the 3 drug regimen, everyone who participates will receive the same dose of the study drug, dasatinib and the 2 standard drugs, fludarabine and rituximab.
- Participants will receive the drugs dasatinib, fludarabine, and rituximab at the following time points through each cycle of treatment. A cycle of study treatment is 28 days. Dasatinib pills will be taken orally each day for the first 2 weeks of each cycle. Fludarabine will be give intravenously on three days of each cycle (Days 3-5 in the first cycle, days 1-3 after that). Rituximab will be given intravenously with a total dose of 375 mg/m2 each cycle (split on Days 3+4 in the first cycle and at the discretion of the treating physician after that on Days 1-3).
- The following procedures will be repeated throughout the study: medical history review; physical exam; performance status test; blood tests and EKG. They will occur daily during the first week of treatment, then weekly for the rest of cycle 1. After cycle 1 these procedures will be done once a week for 4 weeks then once a month for 6 months.
- Tumor assessments will be repeated once every 2 months for the first six months of the study, and then once every 6 months after that.
- Blood samples will be obtained in the first 5 days of treatment for pharmacokinetic studies and pharmacodynamic studies.
- Participants that are benefiting from the study treatment after the first cycle can continue to receive an additional 6 cycles of study treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| dasatinib, rituximab, fludarabine | Other | Drug: dasatinib, Drug: Rituximab, Drug: fludarabineSingle-arm, open-label |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- CLL/SLL with cells positive by flow cytometry (or immunostaining) for CD19, CD23, and CD5. Patients may be CD23 negative as long as they are also cyclin D1 negative or t(11;14) negative.
- Participants must have received at least 1 prior regimen containing a purine analogue or have received at least 2 chemotherapy regimens not containing a purine analogue. Patients may be refractory to single-agent purine analogue treatment, but patients may not be refractory to a combination of purine analogue with rituximab. Patients may have received rituximab.
- 18 years of age or older
- Able to take oral medications
- ECOG Performance Status of 2 or better
Key exclusion criteria (12 listed)
- Pregnant or breastfeeding women
- Uncontrolled angina, congestive heart failure, or MI within 6 months
- Diagnosed or suspected congenital long QT syndrome
- Any history of clinically significant ventricular arrhythmias
- Prolonged QTc interval on pre-entry ECG
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 |
|---|---|---|
| dasatinibTaken orally once a day on days 1-14 of each 28-day cycle | Drug | dasatinib, rituximab, fludarabine |
| RituximabGiven intravenously, 375 mg/m2 each cycle (dose split, given on Days 3+4 of cycle 1, variable after that). | Drug | dasatinib, rituximab, fludarabine |
| fludarabineGiven intravenously, 25 mg/m2/day, for 3 doses per cycle (Days 3-5 in cycle 1, Days 1-3 after that) | Drug | dasatinib, rituximab, fludarabine |
Primary outcome
Response Rate
Time frame: 2 years
To describe the response rate of complete response (CR) and partial response (PR) to treatment with this drug combination (SD=stable disease, PD=progressive disease)
2 secondary outcomes
Progression-Free and Overall Survival
Time frame: 2 years
Toxicities
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. I do not plan to share IPD.
Related trials for Chronic Lymphocytic Leukemia
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Not yet recruitingPhase 2
Nemtabrutinib for Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Leukemia (SLL) Refractory to Covalent Bruton Tyrosine Kinase Inhibitor or Pirtobrutinib and Previously Treated With a BCL2 Inhibitor
Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia
RecruitingObservational study
Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL)
Waldenstrom Macroglobulinemia, Lymphoplasmacytic Lymphoma
RecruitingPhase 3
A Study of Nemtabrutinib Plus Venetoclax vs Venetoclax + Rituximab (VR) in Second-line (2L) + Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (MK-1026-010/BELLWAVE-010).
Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Chronic Lymphocytic
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.
Philip Amrein, MD principal investigator
Massachusetts General Hospital
3 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 dasatinib, Rituximab and fludarabine in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Massachusetts General Hospital at 3 sites 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 10 inclusion and 12 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 14 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 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?
Yes. Results are posted in the registry (first posted 20 Mar 2017). 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?
Response Rate (time frame: 2 years). 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 14 Apr 2017.