Recurrent Follicular LymphomaPhase 1/2NCT01381692
Bortezomib, Rituximab, and Dexamethasone With or Without Temsirolimus in Treating Patients With Untreated or Relapsed Waldenstrom Macroglobulinemia or Relapsed or Refractory Mantle Cell or Follicular Lymphoma
A Phase 1/2 study testing Bortezomib, Dexamethasone and Laboratory Biomarker Analysis in people with Recurrent Follicular Lymphoma and Recurrent Mantle Cell Lymphoma, run by National Cancer Institute (NCI) at 11 sites in United States.
Trial summary
This randomized phase I/II trial studies the side effects and the best dose of temsirolimus when given together with bortezomib, rituximab, and dexamethasone and to see how well they work compared to bortezomib, rituximab, and dexamethasone alone in treating patients with untreated or relapsed Waldenstrom… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma
- What is being tested?
- Bortezomib, Dexamethasone and Laboratory Biomarker Analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 11 sitesUnited States
- Study dates
- 20 Jul 2011to 1 Sep 2021
- Phase
- Phase 1/2
- 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
- Histologically proven diagnosis
- For phase I portion (Arm A, B, C and D), patients must have of one of the following:
- Relapsed Waldenstrom's macroglobulinemia
- Relapsed/refractory mantle cell lymphoma; previous treatment with at least one standard regimen and no longer responsive to that regimen
- Relapsed/refractory follicular lymphoma; previous treatment with at least one standard regimen and no longer responsive to that regimen
- Relapsed/refractory marginal zone lymphoma; previous treatment with at least one standard regimen and no longer responsive to that regimen
Show all 54Show fewer
- Relapsed/refractory small lymphocytic lymphoma; previous treatment with at least one standard regimen and no longer responsive to that regimen
- For phase II portion (Arm E and F), patients must have a diagnosis of symptomatic Waldenstrom's macroglobulinemia, either untreated or relapsed, confirmed by the presence of all of the following:
- Bone marrow lymphoplasmacytosis with
- >= 10% lymphoplasmatic cells (measured within 28 days prior to registration) OR
- Aggregates or sheets of one of the following: lymphocytes, plasma cells or lymphoplasmacytic cells on the bone marrow biopsy (measured within 28 days prior to registration)
- Measurable disease defined as a quantitative immunoglobulin M (IgM) monoclonal protein of >= 1000 mg/dL obtained within 28 days prior to registration
- Cluster of differentiation 20 (CD20) positive bone marrow or lymph node by immunohistochemistry or flow cytometry obtained within 28 days prior to registration
- Lymph node biopsy must be done =< 28 days prior to registration if used as an eligibility criterion for study entry
- Serum protein electrophoresis (SPEP) is required to be performed within 28 days prior to registration
- Additional requirements for Waldenstrom's macroglobulinemia (WM) patients (phase I and II):
- In addition to measurable disease, patients must have symptomatic disease defined by one or more of the following:
- Laboratory studies defining eligibility (hemoglobin [Hgb], platelet count, viscosity) must have been obtained within 28 days prior to registration; if more than one test was obtained, the most recent one will be utilized
- Hemoglobin =< 11 g/dL
- Hyperviscosity syndrome or measured viscosity level of >= 4 centipoise
- NOTE: for these patients it is strongly recommended that they undergo therapeutic plasmapheresis prior to initiation of therapy
- Platelet count < 100,000/mm^3
- Symptomatic lymphadenopathy, splenomegaly, or hepatomegaly
- Constitutional symptoms including fever, night sweats, or unexplained weight loss (at least 10% of body weight in < 6 months)
- Symptomatic cryoglobulinemia
- Additional requirements for WM patients (phase I):
- Patients must have received previous treatment with at least one standard regimen and are no longer responsive to that regimen
- There must have been at least 21 days since the last regimen and patient must have recovered from any previous treatment-related toxicity to =< grade 1
- Additional requirements for WM patients (phase II):
- For previously treated patients, no more than 4 prior regimens are allowed
- If last regimen is with rituximab there must have been at least 6 months since last rituximab dose, and if without rituximab there must have been at least 3 months since last regimen
- For all phase I patients, there must have been at least 21 days since last regimen and any previous non-hematologic treatment related toxicity must have resolved to =< grade 1
- Patients must not be receiving concurrent steroids > 10 mg prednisone (or equivalent) per day
- Prior irradiation is allowed if >= 28 days prior to registration have elapsed since the date of last treatment
- Fasting serum cholesterol =< 300 mg/dL OR =< 7.75 mmol/L AND fasting triglycerides =< 2.5 x institutional upper limit of normal (ULN), within 28 days prior to registration
- NOTE: in case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication; patients cannot be enrolled if they do not meet these criteria on or off lipid lowering medication; patients must start lipid lowering medication and cholesterol and triglycerides must be below said levels before study entry
- Patients must not have had prior exposure to mammalian target of rapamycin (m-TOR) inhibitors (sirolimus, temsirolimus, everolimus)
- Women must not be pregnant or breast-feeding; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
- Women of childbearing potential and sexually active males must use an accepted and effective method of contraception throughout the study and for 8 weeks following discontinuation of everolimus
- Patients must have no history of prior malignancy except for adequately treated basal cell or squamous cell skin cancer or in-situ cervical cancer; the patient may also have had other cancer for which the patient was curatively treated with surgery alone and from which the patient has been disease free for >= 5 years
- Platelets >= 75,000 mm^3
- Neutrophils >= 1,000 mm^3
- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x institutional ULN
- Direct bilirubin =< 1.5 mg/dL
- Serum creatinine =< 2.5 mg/dL
- Patients must be tested for hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) within 28 days of registration and will not be eligible if found to be positive
- Patients must not have any severe and/or uncontrolled medical condition or other conditions that could affect their participation in the study, including, but not restricted to:
- Symptomatic congestive heart failure of New York Heart Association class III or IV
- Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 3 months of start of study treatment, serious uncontrolled cardiac arrhythmia or any other clinically significant heart disease
- Severely impaired lung function as defined as spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for Hgb) that is < 50% of the normal predicted value and/or oxygen (O2) saturation < 88% at rest on room air
- Active (acute or chronic) or uncontrolled severe infections
- Patients must have Eastern Cooperative Oncology Group (ECOG)-American College of Radiology Imaging Network (ACRIN) performance status of =< 2
- Patients must not have grade 2 or higher neuropathy
- Patients must not have concurrent use of angiotensin-converting enzyme (ACE) inhibitors (angioedema), and no concurrent use of strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers and inhibitors
Who cannot join
None listed.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322
Geisinger Medical Center
Danville, Pennsylvania, 17822
Presbyterian - Saint Lukes Medical Center - Health One
Denver, Colorado, 80218
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, 54601
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Marshfield Clinic-Minocqua Center
Minocqua, Wisconsin, 54548
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
Official title: A Randomized Phase I/II Study of Bortezomib, Rituximab, Dexamethasone and Temsirolimus in Patients With Relapsed Waldenstrom Macroglobulinemia and Relapsed/Refractory Mantle Cell, Follicular, Marginal Zone or Small Lymphocytic Lymphomas (Phase I), and Untreated/Relapsed Waldenstrom Macroglobulinemia (Phase II)
This randomized phase I/II trial studies the side effects and the best dose of temsirolimus when given together with bortezomib, rituximab, and dexamethasone and to see how well they work compared to bortezomib, rituximab, and dexamethasone alone in treating patients with untreated or relapsed Waldenstrom macroglobulinemia or relapsed or refractory mantle cell or follicular lymphoma. Bortezomib and temsirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Bortezomib may also stop the growth of cancer cells by blocking blood flow to the tumor. Monoclonal antibodies, such as rituximab, can block cancer growth in difference ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It is not yet known whether bortezomib, rituximab, and dexamethasone are more effective with temsirolimus in treating non-Hodgkin lymphoma.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) of temsirolimus in combination with bortezomib, rituximab, dexamethasone in patients with relapsed Waldenstrom's macroglobulinemia and relapsed/refractory mantle cell, follicular, marginal zone or small lymphocytic lymphoma. (Phase I) II. To evaluate whether the addition of temsirolimus to the regimen of bortezomib, rituximab, dexamethasone improves progression-free survival in patients with previously untreated or relapsed Waldenstrom's macroglobulinemia. (Phase II)
SECONDARY OBJECTIVES:
- To define and describe the toxicities of temsirolimus in combination with bortezomib, rituximab, and dexamethasone. (Phase I) II. To evaluate time to progression of bortezomib, rituximab, dexamethasone +/- temsirolimus in patients. (Phase II) III. To evaluate major and minor response by 6 cycles of therapy of bortezomib, rituximab, dexamethasone +/- temsirolimus. (Phase II) IV. To evaluate time to response and duration of response of bortezomib, rituximab, dexamethasone +/- temsirolimus. (Phase II) V. To evaluate toxicity of bortezomib, rituximab, dexamethasone +/- temsirolimus. (Phase II) VI. To evaluate time to next therapy of bortezomib, rituximab, dexamethasone +/- temsirolimus. (Phase II) VII. To evaluate overall survival of bortezomib, rituximab, dexamethasone +/- temsirolimus. (Phase II) VIII. To describe treatment-related fatigue, physical and functional well-being during and after treatment. (Phase II) IX. To compare the change in treatment related fatigue, physical and functional well-being over 6 cycles of bortezomib, rituximab, dexamethasone +/- temsirolimus. (Quality of Life) X. To prospectively assess health-related quality of life longitudinally (pre-treatment to 3 year follow-up assessment) among trial participants. (Quality of Life) XI. To describe treatment-related peripheral neuropathy associated with bortezomib neurotoxicity. (Quality of Life)
OUTLINE: This is a phase I, dose-escalation study of temsirolimus followed by a randomized phase II study.
PHASE I: Patients receive temsirolimus intravenously (IV) over 30-60 minutes on days 1, 8, 15, and 22; rituximab IV over 30-60 minutes on days 1, 8, 15, and 22 (of courses 1 and 4 only); and bortezomib IV or subcutaneously (SC) and dexamethasone orally (PO) on days 1, 8, and 15. Courses repeat every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
PHASE II: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive rituximab IV over 30-60 minutes on days 1, 8, 15, and 22 (of courses 1 and 4 only) and bortezomib IV or SC and dexamethasone PO on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive temsirolimus IV over 30-60 minutes on days 1, 8, 15, and 22 and rituximab, bortezomib, and dexamethasone as in arm I. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then yearly for 5 years.
- Conditions
- Recurrent Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Small Lymphocytic Lymphoma, Recurrent Waldenstrom Macroglobulinemia
- Being tested
- Bortezomib, Dexamethasone, Laboratory Biomarker Analysis, Quality-of-Life Assessment, Rituximab
- Medical subject headings
- Lymphoma, Follicular, Lymphoma, Mantle-Cell, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Non-Hodgkin, Leukemia, Lymphocytic, Chronic, B-Cell, Waldenstrom Macroglobulinemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
Also called [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341
Given IV or SC
DexamethasoneDrug
Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
RituximabBiological
Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody
Given IV
TemsirolimusDrug
Also called CCI-779, CCI-779 Rapamycin Analog, Cell Cycle Inhibitor 779, Rapamycin Analog
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Arm I (rituximab, bortezomib, dexamethasone) | Active comparator | Patients receive rituximab IV over 30-60 minutes on days 1, 8, 15, and 22 (of courses 1 and 4 only) and bortezomib IV or SC and dexamethasone PO on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: Bortezomib; Drug: Dexamethasone; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Biological: Rituximab |
| Arm II (temsirolimus, rituximab, bortezomib, dexamethasone) | Experimental | Patients receive temsirolimus IV over 30-60 minutes on days 1, 8, 15, and 22 and rituximab, bortezomib, and dexamethasone as in arm I. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: Bortezomib; Drug: Dexamethasone; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Biological: Rituximab; Drug: Temsirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: The Maximum Tolerated Dose (MTD) of Temsirolimus in Combination With Bortezomib, Rituximab and Dexamethasone
Temsirolimus in combination with bortezomib, rituximab, dexamethasone were to be escalated using a standard 3+3 design. The MTD was defined as the highest dose level at which no more than 0 in 3 or 1 in 6 participants experienced a dose-limiting toxicity (DLT) during the first 28-day cycle of treatment.
Measured: Assessed during cycle 1 (28 days)
Phase II: Progression-free Survival
Progression-free survival is defined as the time from randomization to progression or death, whichever occurred first.
Progression is evaluated based on Recommended Response Criteria for Waldenstrom's Macroglobulinemia. Progression is defined as at least 25% increase in serum monoclonal IgM protein by electrophoresis confirmed by a second measurement at any time, as well as an absolute increase of the M-spike by 0.5g/dL, or progression of clinically significant findings due to disease, (i.e. anemia, thrombocytopenia, leukopenia, bulky adenopathy/organomegaly or symptoms of disease) or hyperviscosity, neuropathy, symptomatic cryoglobulinemia, or amyloidosis attributable to WM.
Measured: Assessed every 3 months if <2 years from study entry, every 6 months if 2-5 years from study entry, and annually if 6-10 years
Secondary outcomes (7)
Phase II: Time to Progression
Time to progression is defined as the time from randomization to disease progression.
Progression is evaluated based on Recommended Response Criteria for Waldenstrom's Macroglobulinemia. Progression is defined as at least 25% increase in serum monoclonal IgM protein by electrophoresis confirmed by a second measurement at any time, as well as an absolute increase of the M-spike by 0.5g/dL, or progression of clinically significant findings due to disease, (i.e. anemia, thrombocytopenia, leukopenia, bulky adenopathy/organomegaly or symptoms of disease) or hyperviscosity, neuropathy, symptomatic cryoglobulinemia, or amyloidosis attributable to WM.
Measured: Assessed every 3 months if <2 years from study entry, every 6 months if 2-5 years from study entry, and annually if 6-10 years
Phase II: Major Response Rate
Response is evaluated based on Recommended Response Criteria for Waldenstrom's Macroglobulinemia (WM). Major response is defined as complete response (CR), near CR (nCR), very good partial remission (VGPR), or partial response (PR).
CR: Disappearance of monoclonal protein by immmunofixation; no histologic evidence of bone marrow involvement, resolution of any adenopathy/organomegaly, or signs or symptoms attributable to WM Near CR (nCR): As for CR except that immunofixation is still positive VGPR: At least 90% reduction of serum monoclonal protein using serum protein electrophoresis (SPEP) PR: At least 50% reduction of serum monoclonal concentration on protein electrophoresis and at least a decrease in adenopathy/organomegaly (confirmed by original mode of imaging). No new signs or symptoms of active disease.
Measured: Assessed at cycle 6
Phase II: Minor Response Rate
Response is evaluated based on Recommended Response Criteria for Waldenstrom's Macroglobulinemia (WM). Minor response is defined as achieving minor response (MR) or better (including complete response [CR], near CR (nCR), very good partial remission [VGPR], partial response [PR] and MR).
CR: Disappearance of monoclonal protein by immmunofixation; no histologic evidence of bone marrow involvement, resolution of any adenopathy/organomegaly, or signs or symptoms attributable to WM nCR: As CR except that immunofixation is still positive VGPR: At least 90% reduction of serum monoclonal protein using serum protein electrophoresis PR: At least 50% reduction of serum monoclonal concentration on protein electrophoresis and at least a decrease in adenopathy/organomegaly (confirmed by original mode of imaging). No new signs or symptoms of active disease.
MR: At least 25% but less than 50% reduction of serum monoclonal protein and no new signs or symptoms of active disease.
Measured: Assessed at cycle 6
Phase II: Time to Response
Time to response is defined as the time from randomization to documentation of response. Response is evaluated based on Recommended Response Criteria for Waldenstrom's Macroglobulinemia (WM). Response is defined as complete response (CR), near CR (nCR), very good partial remission (VGPR), partial response (PR) or minor response (MR).
CR: Disappearance of monoclonal protein by immmunofixation; no histologic evidence of bone marrow involvement, resolution of any adenopathy/organomegaly, or signs or symptoms attributable to WM nCR: As CR except that immunofixation is still positive VGPR: >=90% reduction of serum monoclonal protein using serum protein electrophoresis PR: >=50% reduction of serum monoclonal concentration on protein electrophoresis and at least a decrease in adenopathy/organomegaly (confirmed by original mode of imaging). No new signs or symptoms of active disease.
MR: >=25% but <50% reduction of serum monoclonal protein. No new signs or symptoms of active disease
Measured: Assessed every 3 months if <2 years of study entry, every 6 months if 2-5 years of study entry, and annually if 6-10 years
Phase II: Duration of Response
Duration of response is defined as the time from documentation of response to disease progression. Response evaluation will be based on the Recommended Response Criteria for Waldenstrom's Macroglobulinemia (WM).
Response is defined as complete response (CR), near CR (nCR), very good partial remission (VGPR), partial response (PR) or minor response (MR). Progression is defined as at least 25% increase in serum monoclonal IgM protein by electrophoresis confirmed by a second measurement at any time, as well as an absolute increase of the M-spike by 0.5g/dL, or progression of clinically significant findings due to disease, or hyperviscosity, neuropathy, symptomatic cryoglobulinemia, or amyloidosis attributable to WM.
Measured: Assessed every 3 months if <2 years of study entry, every 6 months if 2-5 years of study entry, and annually if 6-10 years
Phase II: Time to Next Therapy
Time to next therapy is defined as duration from the end of protocol treatment to the initiation of next therapy, censored at date last known alive without initiation of next therapy.
Measured: Assessed every 3 months if <2 years of study entry, every 6 months if 2-5 years of study entry, and annually if 6-10 years
Phase II: Overall Survival
Overall survival is defined as the time from randomization to date of death or date last known alive.
Measured: Assessed every 3 months if <2 years of study entry, every 6 months if 2-5 years of study entry, and annually if 6-10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2011 (estimated)
- Study start20 Jul 2011
- Primary completion8 Dec 2014
- Study completion1 Sep 2021
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 Recurrent Follicular LymphomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Leonard T Heffner, Principal investigator, ECOG-ACRIN Cancer Research Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01381692
- Sponsor's protocol ID
- NCI-2011-02650
- Other IDs
- NCI-2011-02650, CDR0000701362, ECOG-E1A10, E1A10, E1A10, E1A10, U10CA180820, U10CA021115
- Status last verified
- Sep 2021
- First submitted
- 23 Jun 2011
- Last updated
- 4 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase I/II Study of Bortezomib, Rituximab, Dexamethasone and Temsirolimus in Patients With Relapsed Waldenstrom Macroglobulinemia and Relapsed/Refractory Mantle Cell, Follicular, Marginal Zone or Small Lymphocytic Lymphomas (Phase I), and Untreated/Relapsed Waldenstrom Macroglobulinemia (Phase II)
- ClinicalTrials.gov ID
- NCT01381692
- Acronym / sponsor ID
- NCI-2011-02650
- Conditions
- Recurrent Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Small Lymphocytic Lymphoma, Recurrent Waldenstrom Macroglobulinemia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 20 Jul 2011 (actual)
- Primary completion
- 8 Dec 2014 (actual)
- Study completion
- 1 Sep 2021 (actual)
- First posted
- 27 Jun 2011 (estimated)
- Results
- Posted 5 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized phase I/II trial studies the side effects and the best dose of temsirolimus when given together with bortezomib, rituximab, and dexamethasone and to see how well they work compared to bortezomib, rituximab, and dexamethasone alone in treating patients with untreated or relapsed Waldenstrom macroglobulinemia or relapsed or refractory mantle cell or follicular lymphoma. Bortezomib and temsirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Bortezomib may also stop the growth of cancer cells by blocking blood flow to the tumor. Monoclonal antibodies, such as rituximab, can block cancer growth in difference ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It is not yet known whether bortezomib, rituximab, and dexamethasone are more effective with temsirolimus in treating non-Hodgkin lymphoma.
Detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) of temsirolimus in combination with bortezomib, rituximab, dexamethasone in patients with relapsed Waldenstrom's macroglobulinemia and relapsed/refractory mantle cell, follicular, marginal zone or small lymphocytic lymphoma. (Phase I) II. To evaluate whether the addition of temsirolimus to the regimen of bortezomib, rituximab, dexamethasone improves progression-free survival in patients with previously untreated or relapsed Waldenstrom's macroglobulinemia. (Phase II)
SECONDARY OBJECTIVES:
- To define and describe the toxicities of temsirolimus in combination with bortezomib, rituximab, and dexamethasone. (Phase I) II. To evaluate time to progression of bortezomib, rituximab, dexamethasone +/- temsirolimus in patients. (Phase II) III. To evaluate major and minor response by 6 cycles of therapy of bortezomib, rituximab, dexamethasone +/- temsirolimus. (Phase II) IV. To evaluate time to response and duration of response of bortezomib, rituximab, dexamethasone +/- temsirolimus. (Phase II) V. To evaluate toxicity of bortezomib, rituximab, dexamethasone +/- temsirolimus. (Phase II) VI. To evaluate time to next therapy of bortezomib, rituximab, dexamethasone +/- temsirolimus. (Phase II) VII. To evaluate overall survival of bortezomib, rituximab, dexamethasone +/- temsirolimus. (Phase II) VIII. To describe treatment-related fatigue, physical and functional well-being during and after treatment. (Phase II) IX. To compare the change in treatment related fatigue, physical and functional well-being over 6 cycles of bortezomib, rituximab, dexamethasone +/- temsirolimus. (Quality of Life) X. To prospectively assess health-related quality of life longitudinally (pre-treatment to 3 year follow-up assessment) among trial participants. (Quality of Life) XI. To describe treatment-related peripheral neuropathy associated with bortezomib neurotoxicity. (Quality of Life)
OUTLINE: This is a phase I, dose-escalation study of temsirolimus followed by a randomized phase II study.
PHASE I: Patients receive temsirolimus intravenously (IV) over 30-60 minutes on days 1, 8, 15, and 22; rituximab IV over 30-60 minutes on days 1, 8, 15, and 22 (of courses 1 and 4 only); and bortezomib IV or subcutaneously (SC) and dexamethasone orally (PO) on days 1, 8, and 15. Courses repeat every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
PHASE II: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive rituximab IV over 30-60 minutes on days 1, 8, 15, and 22 (of courses 1 and 4 only) and bortezomib IV or SC and dexamethasone PO on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive temsirolimus IV over 30-60 minutes on days 1, 8, 15, and 22 and rituximab, bortezomib, and dexamethasone as in arm I. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then yearly for 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (rituximab, bortezomib, dexamethasone) | Active comparator | Drug: Bortezomib, Drug: Dexamethasone, Other: Laboratory Biomarker Analysis, Other: Quality-of-Life Assessment, Biological: RituximabPatients receive rituximab IV over 30-60 minutes on days 1, 8, 15, and 22 (of courses 1 and 4 only) and bortezomib IV or SC and dexamethasone PO on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. |
| Arm II (temsirolimus, rituximab, bortezomib, dexamethasone) | Experimental | Drug: Bortezomib, Drug: Dexamethasone, Other: Laboratory Biomarker Analysis, Other: Quality-of-Life Assessment, Biological: Rituximab, Drug: TemsirolimusPatients receive temsirolimus IV over 30-60 minutes on days 1, 8, 15, and 22 and rituximab, bortezomib, and dexamethasone as in arm I. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (54 listed)
- Histologically proven diagnosis
- For phase I portion (Arm A, B, C and D), patients must have of one of the following:
- For phase II portion (Arm E and F), patients must have a diagnosis of symptomatic Waldenstrom's macroglobulinemia, either untreated or relapsed, confirmed by the presence of all of the following:
- Additional requirements for Waldenstrom's macroglobulinemia (WM) patients (phase I and II):
- In addition to measurable disease, patients must have symptomatic disease defined by one or more of the following:
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| BortezomibAlso: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341Given IV or SC | Drug | Arm I (rituximab, bortezomib, dexamethasone), Arm II (temsirolimus, rituximab, bortezomib, dexamethasone) |
| DexamethasoneAlso: Aacidexam, Adexone, Aknichthol Dexa, Alba-DexGiven PO | Drug | Arm I (rituximab, bortezomib, dexamethasone), Arm II (temsirolimus, rituximab, bortezomib, dexamethasone) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Arm I (rituximab, bortezomib, dexamethasone), Arm II (temsirolimus, rituximab, bortezomib, dexamethasone) |
| Quality-of-Life AssessmentAlso: Quality of Life AssessmentAncillary studies | Other | Arm I (rituximab, bortezomib, dexamethasone), Arm II (temsirolimus, rituximab, bortezomib, dexamethasone) |
| RituximabAlso: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 AntibodyGiven IV | Biological | Arm I (rituximab, bortezomib, dexamethasone), Arm II (temsirolimus, rituximab, bortezomib, dexamethasone) |
| TemsirolimusAlso: CCI-779, CCI-779 Rapamycin Analog, Cell Cycle Inhibitor 779, Rapamycin AnalogGiven IV | Drug | Arm II (temsirolimus, rituximab, bortezomib, dexamethasone) |
Primary outcome
Phase I: The Maximum Tolerated Dose (MTD) of Temsirolimus in Combination With Bortezomib, Rituximab and Dexamethasone
Time frame: Assessed during cycle 1 (28 days)
Temsirolimus in combination with bortezomib, rituximab, dexamethasone were to be escalated using a standard 3+3 design. The MTD was defined as the highest dose level at which no more than 0 in 3 or 1 in 6 participants experienced a dose-limiting toxicity (DLT) during the first 28-day cycle of treatment.
Phase II: Progression-free Survival
Time frame: Assessed every 3 months if <2 years from study entry, every 6 months if 2-5 years from study entry, and annually if 6-10 years
Progression-free survival is defined as the time from randomization to progression or death, whichever occurred first. Progression is evaluated based on Recommended Response Criteria for Waldenstrom's Macroglobulinemia. Progression is defined as at least 25% increase in serum monoclonal IgM protein by electrophoresis confirmed by a second measurement at any time, as well as an absolute increase of the M-spike by 0.5g/dL, or progression of clinically significant findings due to disease, (i.e. anemia, thrombocytopenia, leukopenia, bulky adenopathy/organomegaly or symptoms of disease) or hyperviscosity, neuropathy, symptomatic cryoglobulinemia, or amyloidosis attributable to WM.
7 secondary outcomes
Phase II: Time to Progression
Time frame: Assessed every 3 months if <2 years from study entry, every 6 months if 2-5 years from study entry, and annually if 6-10 years
Phase II: Major Response Rate
Time frame: Assessed at cycle 6
Phase II: Minor Response Rate
Time frame: Assessed at cycle 6
Phase II: Time to Response
Time frame: Assessed every 3 months if <2 years of study entry, every 6 months if 2-5 years of study entry, and annually if 6-10 years
Phase II: Duration of Response
Time frame: Assessed every 3 months if <2 years of study entry, every 6 months if 2-5 years of study entry, and annually if 6-10 years
Phase II: Time to Next Therapy
Time frame: Assessed every 3 months if <2 years of study entry, every 6 months if 2-5 years of study entry, and annually if 6-10 years
Phase II: Overall Survival
Time frame: Assessed every 3 months if <2 years of study entry, every 6 months if 2-5 years of study entry, and annually if 6-10 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2021.
- 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.
Leonard T Heffner principal investigator
ECOG-ACRIN Cancer Research Group
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Bortezomib, Dexamethasone and Laboratory Biomarker Analysis in people with Recurrent Follicular Lymphoma and Recurrent Mantle Cell Lymphoma, run by National Cancer Institute (NCI) at 11 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 54 inclusion and 0 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 4 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 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 combined 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.
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 5 May 2021). 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?
Phase I: The Maximum Tolerated Dose (MTD) of Temsirolimus in Combination With Bortezomib, Rituximab and Dexamethasone (time frame: Assessed during cycle 1 (28 days)). The study lists 2 primary outcomes in all. 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 4 Oct 2021; AzTrials last refreshed its copy on 7 Nov 2026.