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Phase 2 N=9 Randomized Treatment

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

Recurrent Follicular Lymphoma · Recurrent Mantle Cell Lymphoma · Recurrent Marginal Zone Lymphoma · Recurrent Non-Hodgkin Lymphoma · Recurrent Small Lymphocytic Lymphoma

Enrolled (actual)
9
Serious AEs
88.9%
Results posted
May 2021
Primary outcome: Primary: Phase I: The Maximum Tolerated Dose (MTD) of Temsirolimus in Combination With Bortezomib, Rituximab and Dexamethasone — NA; NA mg

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
Bortezomib (Drug); Dexamethasone (Drug); Laboratory Biomarker Analysis (Other); Quality-of-Life Assessment (Other); Rituximab (Biological); Temsirolimus (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
National Cancer Institute (NCI)
Primary completion
Dec 2014

Outcome Measures

OutcomeResultp-value
PRIMARY
Phase I: The Maximum Tolerated Dose (MTD) of Temsirolimus in Combination With Bortezomib, Rituximab and Dexamethasone
NA; NA
PRIMARY
Phase II: Progression-free Survival
SECONDARY
Phase II: Time to Progression
SECONDARY
Phase II: Major Response Rate
SECONDARY
Phase II: Minor Response Rate
SECONDARY
Phase II: Time to Response
SECONDARY
Phase II: Duration of Response
SECONDARY
Phase II: Time to Next Therapy
SECONDARY
Phase II: Overall Survival

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 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.

Eligibility Criteria

Inclusion Criteria

  • 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
  • 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 = = 4 centipoise
  • NOTE: for these patients it is strongly recommended that they undergo therapeutic plasmapheresis prior to initiation of therapy
  • Platelet count 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 = = 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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01381692). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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