Trial · NCT01125293
Everolimus, Bortezomib and/or Rituximab in Patients With Relapsed/Refractory Waldenstrom's Macroglobulinemia
NCT01125293, Phase 1, Phase 2, Terminated, Dana-Farber Cancer Institute; results first posted 2021-04-23
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Everolimus, Bortezomib and/or Rituximab in Patients With Relapsed/Refractory Waldenstrom's Macroglobulinemia. Trials, record NCT01125293. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT01125293
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Everolimus, Bortezomib and/or Rituximab in Patients With Relapsed/Refractory Waldenstrom's Macroglobulinemia
- NCT number
- NCT01125293
- Status
- Terminated
- Phases
- Phase 1, Phase 2
- Enrollment
- 46 participants, actual
- Lead sponsor
- Dana-Farber Cancer Institute
- Conditions
- Waldenstrom's Macroglobulinemia
- Interventions
- Everolimus, Rituximab, Bortezomib
- First posted
- 2010-05-18
- Last updated
- 2021-04-23
- Results first posted
- 2021-04-23
Source ClinicalTrials.gov
Registered outcomes10
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Everolimus Maximum Tolerated Dose (MTD) Stage A [Phase I] | Assessed within the first cycle (28 days) of the study. | The MTD of Everolimus/Rituximab combination is determined by the number of patients who have dose limiting toxicity (DLT). See DLT primary outcome measure for definition. MTD is defined as the highest dose where \<1/3 participants experience a DLT. If no DLT's are observed on Level 1, 3 subjects will be enrolled in the Level 2. If \>1/3 subjects in a cohort have DLT, that dose will not be considered safe, with no escalation (MTD exceeded). If 1/3 subjects experience DLT, the cohort will be expanded to 6 subjects. If \<2 subjects with a DLT among the expanded cohort of 6 evaluable subjects a cohort of 3 subjects will be enrolled in the next higher dose level. If 2 or more subjects with a DLT among the expanded cohort of 6 subjects, that dose level will not be considered safe, no escalation (MTD exceeded). If no DLT's are observed, then the MTD is not reached. The MTD was not reached with 0/3 participants experiencing a DLT in the highest dose level. Higher doses were not planned/tested. |
| Primary | Everolimus Maximum Tolerated Dose (MTD) Stage B [Phase I] | Assessed within the first cycle (28 days) of the study. | The MTD of Everolimus/Bortezomib/Rituximab combination is determined by the number of patients who have dose limiting toxicity (DLT). See DLT primary outcome measure for definition. MTD is defined as the highest dose where \<1/3 participants experience a DLT. If no DLT's are observed on Level 1, 3 subjects will be enrolled in the Level 2. If \>1/3 subjects in a cohort have DLT, that dose will not be considered safe, with no escalation (MTD exceeded). If 1/3 subjects experience DLT, the cohort will be expanded to 6 subjects. If \<2 subjects with a DLT among the expanded cohort of 6 evaluable subjects a cohort of 3 subjects will be enrolled in the next higher dose level. If 2 or more subjects with a DLT among the expanded cohort of 6 subjects, that dose level will not be considered safe, no escalation (MTD exceeded).If no DLT's observed, then the MTD is not reached. The MTD was not reached with 0/3 participants experiencing a DLT in the highest level. Higher doses were not planned/tested. |
| Primary | Everolimus Dose Limiting Toxicity (DLT) [Phase I] | Assessed within the first cycle (28 days) of the study. | The following qualify as dose limiting toxicities: * Grade 3 or greater non-hematologic toxicity, considered by the investigator to be related to study drugs. * Grade 4 hematologic toxicity defined as: thrombocytopenia with platelets \<10,000 µ/L on more than one occasion despite transfusion support; grade 4 neutropenia occurring for more than 7 days and/or resulting in neutropenic fever with elevated temperature (defined as \> 101 degrees F). Lymphopenia, a recognized side effect of bortezomib, is not considered a DLT. * Inability to receive Day 1 dose for Cycle 2 due to toxicity |
| Primary | Very-good-partial-response-or-better Rate [Phase II] | Up to 6 cycles (Day 168) | Very-good-partial-response-or-better rate is the percentage of participants with complete response (CR) or very good partial response (VGPR) on to the combination of everolimus/bortezomib/rituximab. The combination regimen was received for up to 6 cycles. CR: * Absence of serum monoclonal IgM protein by immunofixation * Normal serum IgM level * Complete resolution of extramedullary disease, i.e., lymphadenopathy and splenomegaly if present at baseline * Morphologically normal bone marrow aspirate and trephine biopsy VGPR: * Monoclonal IgM protein is detectable ≥90% reduction in serum IgM level from baseline\* * Complete resolution of extramedullary disease, i.e. |
| Secondary | Treatment-Emergent Sensory Neuropathy Rate [Phase I] | Adverse events were assessed each cycle (ever 28 days) for 6 cycles then every 3 months on maintenance. Duration of therapy for the Phase I study up to 41 months. | Percentage of participants experiencing Grade 1 - Grade 3 treatment-emergent peripheral (sensory) neuropathy events based on CTCAEv3 as reported on case report forms for phase I participants. |
| Secondary | Phase II Overall Response Rate | Up to 6 cycles (Day 168) | Overall response rate is percentage of participants with complete (CR), very good partial (VGPR), partial (PR), or minimal response (MR) as best response during treatment. CR: * No serum monoclonal IgM protein by immunofixation * Normal IgM level * Complete resolution of extramedullary disease, i.e., lymphadenopathy and splenomegaly if present at baseline * Morphologically normal bone marrow aspirate and trephine biopsy VGPR: * Monoclonal IgM protein is detectable ≥90% reduction in IgM level from baseline * Complete resolution of extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at baseline * No new signs/symptoms of active disease PR: * Monoclonal IgM protein is detectable ≥50% but \<90% reduction in IgM level from baseline * Reduction in extramedullary disease * No new signs/symptoms of active disease MR: * Monoclonal IgM protein is detectable ≥25% but \<50% reduction in IgM level from baseline * No new signs/symptoms of active disease |
| Secondary | 2-year Time-to-progression Probability (TTP) [Phase II] | Patients were assessed for disease every cycle while on treatment (168 days) and every three months while on maintenance therapy. In long-term follow-up, disease was monitored every 3 months. Study cohort median (range) follow-up was 15 (1 - 23) months. | 2-year TTP probability is based on Kaplan-Meier methods. TTP is defined as time from enrollment to the date of progressive disease (PD). PD is defined as ≥25% increase in serum IgM level from lowest nadir and/or progression in clinical features attributable the disease. Patients without PD and not reporting use of non-protocol therapy prior to PD are censored at date of last objective progression-free disease assessment. Patients reporting use of non-protocol therapy prior to PD are censored at date of last objective progression-free disease assessment date prior to post-discontinuation therapy. |
| Secondary | 2 Year Progression-free-survival [Phase II] | Patients were assessed for disease every cycle while on treatment (168 days) and every three months while on maintenance therapy. In long-term follow-up, disease was monitored every 3 months. Study cohort median (range) follow-up was 15 (1 - 23) months. | 2-year progression free survival (PFS) is the probability of participants alive and progression free at 2 years from study entry estimated using Kaplan-Meier methods. PFS is defined as the time from enrollment to progressive disease (PD) or death. PD is defined as ≥25% increase in serum IgM level from lowest nadir and/or progression in clinical features attributable the disease. Patients alive without PD and not reporting use of non-protocol therapy prior to PD are censored at date of last objective progression-free disease assessment. Patients reporting use of non-protocol therapy prior to PD are censored at date of last objective progression-free disease assessment date prior to post-discontinuation therapy. |
| Secondary | Phase II Duration of Response (DoR) | Patients were assessed for disease every cycle while on treatment (168 days) and every three months while on maintenance therapy. In long-term follow-up, disease was monitored every 3 months. Study cohort median (range) follow-up was 15 (1 - 23) months. | The DoR is defined as the elapsed time from date when the measurement criteria are first met for a complete or partial response (whichever status is recorded first) until the date of first observation of objective disease progression. Analysis of DoR will be as follows: * For responding patients who die without objective PD (including death from study disease), DoR will be censored at the date of the last objective progression-free disease assessment. * For responding patients not known to have died as of the data cut-off date and who do not have objective PD, DoR will be censored at the date of the last objective progression-free disease assessment. * For responding patients who receive subsequent systemic anticancer therapy (after discontinuation from the study chemotherapy) prior to objectively determined disease progression, DoR will be censored at the date of the last objective progression-free disease assessment prior to post discontinuation therapy. |
| Secondary | PTEN Mutation Rate [Phase II] | Samples were collected pre-therapy before the beginning therapy (baseline) and post-therapy after finishing the 6th treatment cycle (168 days). | The PTEN mutation rate is the percentage of patients with PTEN mutation identified in pre-therapy and post-therapy bone marrow samples per established methods. |
Source ClinicalTrials.gov
Outcomes10
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Everolimus Maximum Tolerated Dose (MTD) Stage A [Phase I] | Assessed within the first cycle (28 days) of the study. | The analysis dataset includes all participants enrolled to Stage A. | mg | NUMBER |
| PRIMARY | Everolimus Maximum Tolerated Dose (MTD) Stage B [Phase I] | Assessed within the first cycle (28 days) of the study. | In Phase I Stage B Level 1, one participant was replaced as an exception granted to the principal investigator having experienced a dose delay due to an adverse event not deemed a DLT. | mg | NUMBER |
| PRIMARY | Everolimus Dose Limiting Toxicity (DLT) [Phase I] | Assessed within the first cycle (28 days) of the study. | In Phase I Stage B Level 1, one participant was replaced as an exception granted to the principal investigator having experienced a dose delay due to an adverse event not deemed a DLT. | participants | NUMBER |
| PRIMARY | Very-good-partial-response-or-better Rate [Phase II] | Up to 6 cycles (Day 168) | percentage of participants | NUMBER | |
| SECONDARY | Treatment-Emergent Sensory Neuropathy Rate [Phase I] | Adverse events were assessed each cycle (ever 28 days) for 6 cycles then every 3 months on maintenance. Duration of therapy for the Phase I study up to 41 months. | percentage of participants | NUMBER | |
| SECONDARY | Phase II Overall Response Rate | Up to 6 cycles (Day 168) | percentage of participants | NUMBER | |
| SECONDARY | 2-year Time-to-progression Probability (TTP) [Phase II] | Patients were assessed for disease every cycle while on treatment (168 days) and every three months while on maintenance therapy. In long-term follow-up, disease was monitored every 3 months. Study cohort median (range) follow-up was 15 (1 - 23) months. | percent probability of progression | NUMBER | |
| SECONDARY | 2 Year Progression-free-survival [Phase II] | Patients were assessed for disease every cycle while on treatment (168 days) and every three months while on maintenance therapy. In long-term follow-up, disease was monitored every 3 months. Study cohort median (range) follow-up was 15 (1 - 23) months. | percent probability of PFS | NUMBER | |
| SECONDARY | Phase II Duration of Response (DoR) | Patients were assessed for disease every cycle while on treatment (168 days) and every three months while on maintenance therapy. In long-term follow-up, disease was monitored every 3 months. Study cohort median (range) follow-up was 15 (1 - 23) months. | months | MEDIAN | |
| SECONDARY | PTEN Mutation Rate [Phase II] | Samples were collected pre-therapy before the beginning therapy (baseline) and post-therapy after finishing the 6th treatment cycle (168 days). | The correlative objective for the study was to identify molecular regulators of response/resistance. Because the study terminated early with limited efficacy shown in the stage 1 cohort correlative objectives could not be met. Bone marrow and peripheral blood samples were collected pre- and post-therapy for phase II patients but only a few experiments conducted considering resources and the limited potential interpretation. | percentage of participants | NUMBER |
Source ClinicalTrials.gov
Results by group19
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Everolimus Maximum Tolerated Dose (MTD) Stage A [Phase I] | Phase I Stage A Level 1 and 2 | 10 | mg | ||
| Everolimus Maximum Tolerated Dose (MTD) Stage B [Phase I] | Phase I Stage B Level 1 & 2 and Dose Expansion | 10 | mg | ||
| Everolimus Dose Limiting Toxicity (DLT) [Phase I] | Phase I Stage A Level 1 | 0 | participants | ||
| Everolimus Dose Limiting Toxicity (DLT) [Phase I] | Phase I Stage A Level 2 | 0 | participants | ||
| Everolimus Dose Limiting Toxicity (DLT) [Phase I] | Phase I Stage B Level 1 | 0 | participants | ||
| Everolimus Dose Limiting Toxicity (DLT) [Phase I] | Phase I Stage B Level 2 | 0 | participants | ||
| Very-good-partial-response-or-better Rate [Phase II] | Phase II | 4.3 | 95% Confidence Interval 0 to 19 | percentage of participants | |
| Treatment-Emergent Sensory Neuropathy Rate [Phase I] | Phase I Stage A Level 1 | 33 | 95% Confidence Interval 6 to 80 | percentage of participants | |
| Treatment-Emergent Sensory Neuropathy Rate [Phase I] | Phase I Stage A Level 2 | 33 | 95% Confidence Interval 6 to 80 | percentage of participants | |
| Treatment-Emergent Sensory Neuropathy Rate [Phase I] | Phase I Stage B Level 1 | 100 | 95% Confidence Interval 51 to 100 | percentage of participants |
1 to 10 of 19Source ClinicalTrials.gov
See all 19 results by groupParticipant flow24
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Phase I Stage A Level 1 | 3 | |
| Overall Study | STARTED | Phase I Stage A Level 2 | 3 | |
| Overall Study | STARTED | Phase I Stage B Level 1 | 4 | |
| Overall Study | STARTED | Phase I Stage B Level 2 | 3 | |
| Overall Study | STARTED | Phase I Dose Expansion | 10 | |
| Overall Study | STARTED | Phase II | 23 | |
| Overall Study | Evaluable for Phase I Dose-Limiting Toxicity | Phase I Stage A Level 1 | 3 | |
| Overall Study | Evaluable for Phase I Dose-Limiting Toxicity | Phase I Stage A Level 2 | 3 | |
| Overall Study | Evaluable for Phase I Dose-Limiting Toxicity | Phase I Stage B Level 1 | 3 | |
| Overall Study | Evaluable for Phase I Dose-Limiting Toxicity | Phase I Stage B Level 2 | 3 |
1 to 10 of 24Source ClinicalTrials.gov
See all 24 participant flowAdverse events996
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Febrile neutropenia | Blood and lymphatic system disorders | Phase I Stage A Level 1 | 0 | 3 | |
| other | Febrile neutropenia | Blood and lymphatic system disorders | Phase I Stage A Level 2 | 0 | 3 | |
| other | Febrile neutropenia | Blood and lymphatic system disorders | Phase I Stage B Level 1 | 0 | 4 | |
| other | Febrile neutropenia | Blood and lymphatic system disorders | Phase I Stage B Level 2 | 1 | 3 | |
| other | Febrile neutropenia | Blood and lymphatic system disorders | Phase I Dose Expansion | 0 | 10 | |
| other | Febrile neutropenia | Blood and lymphatic system disorders | Phase II | 0 | 23 | |
| other | Hematologic-other | Blood and lymphatic system disorders | Phase I Stage A Level 1 | 0 | 3 | |
| other | Hematologic-other | Blood and lymphatic system disorders | Phase I Stage A Level 2 | 0 | 3 | |
| other | Hematologic-other | Blood and lymphatic system disorders | Phase I Stage B Level 1 | 0 | 4 | |
| other | Hematologic-other | Blood and lymphatic system disorders | Phase I Stage B Level 2 | 0 | 3 |
1 to 10 of 996Source ClinicalTrials.gov
See all 996 adverse eventsAdverse event totals18
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Phase I Stage A Level 1 | 0 | 3 |
| Total, all-cause mortality | Phase I Stage A Level 2 | 0 | 3 |
| Total, all-cause mortality | Phase I Stage B Level 1 | 0 | 4 |
| Total, all-cause mortality | Phase I Stage B Level 2 | 0 | 3 |
| Total, all-cause mortality | Phase I Dose Expansion | 1 | 10 |
| Total, all-cause mortality | Phase II | 0 | 23 |
| Total, other adverse events | Phase I Stage A Level 1 | 3 | 3 |
| Total, other adverse events | Phase I Stage A Level 2 | 3 | 3 |
| Total, other adverse events | Phase I Stage B Level 1 | 4 | 4 |
| Total, other adverse events | Phase I Stage B Level 2 | 3 | 3 |
1 to 10 of 18Source ClinicalTrials.gov
See all 18 adverse event totalsPapers1
The papers the trial lists on ClinicalTrials.gov.
| PMID | Listed as |
|---|---|
| 26139427 | RESULT |
Source PubMed
Grants1
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
| Project | Title | Principal investigators | Organization | Funder | Fiscal years |
|---|---|---|---|---|---|
| R01FD003743 | NF-KB and mTOR regulation in Waldenstrom Macroglobulinemia | GHOBRIAL, IRENE M. | DANA-FARBER CANCER INST | FOOD AND DRUG ADMINISTRATION | 2010 to 2013 |
Source NIH RePORTER
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT01125293
GET https://conductscience.org/api/trials/v1/NCT01125293/flow?page=2