Waldenstrom's MacroglobulinemiaPhase 2NCT00718419
A Study for Patients That Have Been Previously Been Treated in Waldenstrom's Macroglobulinemia or Multiple Myeloma
A Phase 2 study testing Enzastaurin in people with Waldenstrom's Macroglobulinemia and Multiple Myeloma, run by Eli Lilly and Company at 4 sites in 2 countries.
Trial summary
To determine whether further study of single-agent enzastaurin is warranted in patients with previously treated Waldenstrom's Macroglobulinemia or Multiple Myeloma based on response. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Waldenstrom's Macroglobulinemia, Multiple Myeloma
- What is being tested?
- Enzastaurin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 4 sitesin 2 countries
- Study dates
- Jul 2008to Aug 2012
- 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
- At least 18 years of age.
- Patients must have Waldenstrom's Macroglobulinemia (WM) or Multiple Myeloma (MM) previously treated with at least 1 and no more than 5 prior therapies.
- Treatment with prior autologous transplant is permitted. If a transplant is used as consolidation following chemotherapy, without intervening disease progression, it will be considered 1 line of treatment with the preceding chemotherapy.
- Patients with MM must have a monoclonal protein in the serum of greater than or equal to 1 gram per deciliter (g/dL) or monoclonal light chain in the urine protein electrophoresis of greater than or equal to 200 milligrams (mg)/ 24 hours, or measurable plasmacytoma.
- Patients with WM must have an immunoglobulin M (IgM) paraprotein with a minimum IgM level of > 2 times the upper limit of normal (ULN), have detectable lymphoplasmacytic (LPL) cells in the bone marrow, and be symptomatic for WM.
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1, or 2.
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- The following laboratory values obtained prior to registration:
- Absolute neutrophil count (ANC) greater than or equal to 1000/microliter
- Platelet (PLT) count greater than or equal to 75,000/microliter
- Total bilirubin less than or equal to 1.5 x ULN (if total is elevated check direct and, if normal, patient is eligible)
- Aspartate transaminase (AST) less than or equal to 3 x ULN
- Creatinine less than or equal to 1.5 x ULN
- Hemoglobin (Hgb) greater than or equal to 8.0 g/dL.
- Expected survival of greater than 12 weeks.
- The ability to provide informed consent.
- Male and female patients with reproductive potential must use an approved contraceptive method, if appropriate (for example, intrauterine device [IUD], birth control pills, or barrier device) during and for 3 months after discontinuation of study treatment. Women with childbearing potential must have a negative serum pregnancy test less than or equal to 3 days prior to study enrollment
Who cannot join
- Prior allogeneic hematopoietic stem cell transplant.
- Are unable to discontinue use of non-Enzyme-Inducing Anti-Epileptic Drugs (EIAEDs), for example carbamazepine, phenobarbital, and phenytoin. Patients on anti-coagulant therapy should be monitored. Ongoing treatment with therapeutic doses of Coumadin is prohibited. However, prophylactic, low dose (less than or equal to 2 mg daily) Coumadin for deep venous thrombosis (DVT) is allowed. In such cases, prothrombin time/ international normalized ratio (PT/INR) should be closely monitored.
- Have electrocardiogram (ECG) abnormalities including baseline 12-lead ECG with QTc interval of greater than 450 milliseconds (msec) in males or greater than 470 msec in females, or QRS duration of greater than 100 msec. Patients who have a congenital long-QT-syndrome in their own or family medical history should be excluded at the investigator's discretion.
- Have an uncontrolled infection.
- Have prior treatment with Carmustine (BCNU) 6 weeks, alkylating agent 4 weeks, or other cytotoxic chemotherapy agents 4 weeks prior to registration in this trial. Have prior treatment with biologic therapy less than or equal to 12 weeks or corticosteroids less than or equal to 2 weeks prior to registration in this trial. However, treatment with less than or equal to 10 mg of prednisone as a chronic therapy is allowed.
- Have radiation therapy less than or equal to 2 weeks prior to treatment in this trial.
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- Are pregnant or breast-feeding.
- Are being treated with concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational.
- Are known to be human immunodeficiency virus (HIV) positive.
- Were previously treated with enzastaurin.
- Patients who are unable to swallow tablets.
- Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
- Concurrent malignancy that could complicate interpretation of response or safety evaluation. Non-melanoma skin cancer and carcinoma in situ of the cervix are not exclusions.
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
France3 sites
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
La Roche-sur-Yon, 85925
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Nantes, 44093
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Nîmes, 30029
United States1 site
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Boston, Massachusetts, 02115
About this study
Official title: An Open Label, Multicenter Phase 2 Study of Single-Agent Enzastaurin HCl in Previously Treated Waldenstrom's Macroglobulinemia or Multiple Myeloma
To determine whether further study of single-agent enzastaurin is warranted in patients with previously treated Waldenstrom's Macroglobulinemia or Multiple Myeloma based on response.
- Conditions
- Waldenstrom's Macroglobulinemia, Multiple Myeloma
- Being tested
- Enzastaurin
- Keywords
- Waldenstrom's Macroglobulinemia, Multiple Myeloma
- Medical subject headings
- Waldenstrom Macroglobulinemia, Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EnzastaurinDrug
Also called LY317615
Enzastaurin: Cycle 1 Day 1 only: 3, 125-milligrams (mg) tablets three times on Day 1 (Day 1 total dose = 1125 mg)
Day 2 onwards and subsequent Cycles: 2, 125-mg tablets orally twice a day (500 mg total per day).
Cycle length (all cycles): 28 days. Patients may stay on drug past 8 cycles, (until the study is closed) or until disease progression.
| Study group | Role | What they receive |
|---|---|---|
| A: Enzastaurin | Experimental | Not described Receives: Drug: Enzastaurin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Complete Response (CR), Partial Response (PR) and Minimal Response (MR) or Minor Response (MinR): (Response Rate)
European Group for Blood and Bone Marrow Transplant (EBMT) Response Criteria (RC) used for MM. CR: no serum/urine M protein for 6 weeks (wk), <5% plasma cells in bone marrow (PCBM), no lytic bone lesions (LBL) size/number increase, no soft tissue plasmacytomas (STPC); PR: met some CR criteria plus maintain for 6 wk ≥50% serum monoclonal paraprotein (SPEP) and PCBM decrease, either decrease of ≥90% or <200 mg light chain excretion (LCE), ≥50% STPC size decrease; MR: met some PR criteria plus maintain for 6 wk, a decrease of: 25-49% SPEP, 50-89% 24 hour urinary LCE, 25-49% PCBM, 25-49% STPC size. International Workshop on WM (IWWM) RC used for WM. CR: no serum M protein, malignant cells in BM, or lymphadenopathy/organomegaly; PR: ≥50% immunoglobulin M (IgM) and adenopathy/organomegaly (A/O) decrease; no new symptoms of WM. MinR: ≥25% to <50% IgM decrease, no A/O progression; no cytopenias or clinical symptoms of WM.
Measured: Baseline to measured progressive disease up to 40.51 months
Secondary outcomes (3)
Duration of Response (DOR)
DOR is defined as elapsed time from the first evidence of CR, PR, MR or MinR until date of progression of disease (PD). EBMT RC used for MM. CR: no serum/urine M protein for 6 wk, <5% PCBM, no LBL size/number increase, no STPC; PR: met some CR criteria plus maintain for 6 wk ≥50% SPEP and PCBM decrease, either decrease of ≥90% or <200 mg LCE, ≥50% STPC size decrease; MR: met some PR criteria plus maintain for 6 wk decrease of: 25-49% SPEP, 50-89% 24 hour urinary LCE, 25-49% PCBM, 25-49% STPC size. PD: >25% increase in SPEP, 24 hour urinary LCE, PCBM, STPC size increase, new bone lesion or STPC. IWWM RC used for WM. CR: no serum M protein, malignant cells in BM, or lymphadenopathy/organomegaly; PR: ≥50% IgM and A/O decrease; no new WM symptoms. MinR: ≥25% to <50% IgM decrease, no A/O progression; no cytopenias or clinical of WM symptoms. PD: >25% IgM increase, progression of clinical findings or symptoms. For participants who had no PD, DOR was censored at their last contact.
Measured: Time of response to time of measured progressive disease up to 38.37 months
Time to Progressive Disease
Time to progression is defined as the elapsed time from the date of study enrollment to the date of objectively determined progressive disease (PD). European Group for Blood and Bone Marrow Transplant (EBMT) Response Criteria was used for MM. PD: >25% increase in serum monoclonal paraprotein (SPEP), 24 hour urinary light chain excretion (LCE), plasma cells in bone marrow (PCBM), soft tissue plasmacytomas (STPC) size increase, new bone lesion or STPC. International Workshop on WM (IWWM) Response Criteria was used for WM. PD: >25% immunoglobulin M (IgM) increase, progression of clinical findings or symptoms. For participants who had no PD, time to PD was censored at their last contact.
Measured: Baseline to measured progressive disease up to 40.51 months
Number of Participants With Adverse Events (Safety and Adverse Events)
Data are presented as number of participants who experienced serious adverse events or all other nonserious adverse events during the study including the 30-day follow-up period. A summary of serious adverse events and other nonserious adverse events is located in the Reported Adverse Event section. Safety data were collected up to 24 cycles plus 30 days of follow-up for a total up to 23.40 months.
Measured: Treatment start to 30 days after discontinuation of study treatment up to 23.40 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2008 (estimated)
- Study startJul 2008
- Primary completionSep 2010
- Study completionAug 2012
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 Waldenstrom's MacroglobulinemiaStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe 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
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon- Fri 9 AM- 5 PM Eastern time (UTC/GMT- 5 hours, EST), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00718419
- Sponsor's protocol ID
- 11481
- Other IDs
- H6Q-MC-S042
- Status last verified
- Sep 2020
- First submitted
- 16 Jul 2008
- Last updated
- 3 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Multicenter Phase 2 Study of Single-Agent Enzastaurin HCl in Previously Treated Waldenstrom's Macroglobulinemia or Multiple Myeloma
- ClinicalTrials.gov ID
- NCT00718419
- Acronym / sponsor ID
- 11481
- Conditions
- Waldenstrom's Macroglobulinemia, Multiple Myeloma
- Keywords
- Waldenstrom's Macroglobulinemia, Multiple Myeloma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- Jul 2008
- Primary completion
- Sep 2010 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 18 Jul 2008 (estimated)
- Results
- Posted 3 Sep 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To determine whether further study of single-agent enzastaurin is warranted in patients with previously treated Waldenstrom's Macroglobulinemia or Multiple Myeloma based on response.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| A: Enzastaurin | Experimental | Drug: Enzastaurin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- At least 18 years of age.
- Patients must have Waldenstrom's Macroglobulinemia (WM) or Multiple Myeloma (MM) previously treated with at least 1 and no more than 5 prior therapies.
- Treatment with prior autologous transplant is permitted. If a transplant is used as consolidation following chemotherapy, without intervening disease progression, it will be considered 1 line of treatment with the preceding chemotherapy.
- Patients with MM must have a monoclonal protein in the serum of greater than or equal to 1 gram per deciliter (g/dL) or monoclonal light chain in the urine protein electrophoresis of greater than or equal to 200 milligrams (mg)/ 24 hours, or measurable plasmacytoma.
- Patients with WM must have an immunoglobulin M (IgM) paraprotein with a minimum IgM level of > 2 times the upper limit of normal (ULN), have detectable lymphoplasmacytic (LPL) cells in the bone marrow, and be symptomatic for WM.
Key exclusion criteria (13 listed)
- Prior allogeneic hematopoietic stem cell transplant.
- Are unable to discontinue use of non-Enzyme-Inducing Anti-Epileptic Drugs (EIAEDs), for example carbamazepine, phenobarbital, and phenytoin. Patients on anti-coagulant therapy should be monitored. Ongoing treatment with therapeutic doses of Coumadin is prohibited. However, prophylactic, low dose (less than or equal to 2 mg daily) Coumadin for deep venous thrombosis (DVT) is allowed. In such cases, prothrombin time/ international normalized ratio (PT/INR) should be closely monitored.
- Have electrocardiogram (ECG) abnormalities including baseline 12-lead ECG with QTc interval of greater than 450 milliseconds (msec) in males or greater than 470 msec in females, or QRS duration of greater than 100 msec. Patients who have a congenital long-QT-syndrome in their own or family medical history should be excluded at the investigator's discretion.
- Have an uncontrolled infection.
- Have prior treatment with Carmustine (BCNU) 6 weeks, alkylating agent 4 weeks, or other cytotoxic chemotherapy agents 4 weeks prior to registration in this trial. Have prior treatment with biologic therapy less than or equal to 12 weeks or corticosteroids less than or equal to 2 weeks prior to registration in this trial. However, treatment with less than or equal to 10 mg of prednisone as a chronic therapy is allowed.
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 |
|---|---|---|
| EnzastaurinAlso: LY317615Enzastaurin: Cycle 1 Day 1 only: 3, 125-milligrams (mg) tablets three times on Day 1 (Day 1 total dose = 1125 mg) Day 2 onwards and subsequent Cycles: 2, 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days. Patients may stay on drug past 8 cycles, (until the study is closed) or until disease progression. | Drug | A: Enzastaurin |
Primary outcome
Percentage of Participants With Complete Response (CR), Partial Response (PR) and Minimal Response (MR) or Minor Response (MinR): (Response Rate)
Time frame: Baseline to measured progressive disease up to 40.51 months
European Group for Blood and Bone Marrow Transplant (EBMT) Response Criteria (RC) used for MM. CR: no serum/urine M protein for 6 weeks (wk), <5% plasma cells in bone marrow (PCBM), no lytic bone lesions (LBL) size/number increase, no soft tissue plasmacytomas (STPC); PR: met some CR criteria plus maintain for 6 wk ≥50% serum monoclonal paraprotein (SPEP) and PCBM decrease, either decrease of ≥90% or <200 mg light chain excretion (LCE), ≥50% STPC size decrease; MR: met some PR criteria plus maintain for 6 wk, a decrease of: 25-49% SPEP, 50-89% 24 hour urinary LCE, 25-49% PCBM, 25-49% STPC size. International Workshop on WM (IWWM) RC used for WM. CR: no serum M protein, malignant cells in BM, or lymphadenopathy/organomegaly; PR: ≥50% immunoglobulin M (IgM) and adenopathy/organomegaly (A/O) decrease; no new symptoms of WM. MinR: ≥25% to <50% IgM decrease, no A/O progression; no cytopenias or clinical symptoms of WM.
3 secondary outcomes
Duration of Response (DOR)
Time frame: Time of response to time of measured progressive disease up to 38.37 months
Time to Progressive Disease
Time frame: Baseline to measured progressive disease up to 40.51 months
Number of Participants With Adverse Events (Safety and Adverse Events)
Time frame: Treatment start to 30 days after discontinuation of study treatment up to 23.40 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Lilly Clinical Trial RegistryLink 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.
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon- Fri 9 AM- 5 PM Eastern time (UTC/GMT- 5 hours, EST) study director
Eli Lilly and Company
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Enzastaurin in people with Waldenstrom's Macroglobulinemia and Multiple Myeloma, run by Eli Lilly and Company at 4 sites in 2 countries.
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 16 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 3 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in France, 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 3 Sep 2020). 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?
Percentage of Participants With Complete Response (CR), Partial Response (PR) and Minimal Response (MR) or Minor Response (MinR): (Response Rate) (time frame: Baseline to measured progressive disease up to 40.51 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 3 Sep 2020.