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

NCT01381692 | Completed Phase 1 Results

• 6 other identifiers: NCI-2011-02650CDR0000701362ECOG-E1A10E1A10U10CA180820U10CA021115
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 11

Brief 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.

Conditions

Recurrent Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Recurrent Waldenstrom Macroglobulinemia; Refractory Follicular Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Marginal Zone Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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

  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

  Assessed at cycle 6

• Phase II: Minor Response Rate

  Assessed at cycle 6

• Phase II: Time to Response

  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

  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

Study Arms (2)

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.

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.

Drug: Bortezomib; Drug: Dexamethasone; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Biological: Rituximab; Drug: Temsirolimus

Interventions

Bortezomib DRUG

Given IV or SC

Also known as: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341, PS341, Velcade

Arm I (rituximab, bortezomib, dexamethasone); Arm II (temsirolimus, rituximab, bortezomib, dexamethasone)

Dexamethasone DRUG

Given PO

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Dxevo, Fluorodelta, Fortecortin, Gammacorten, Hemady, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Arm I (rituximab, bortezomib, dexamethasone); Arm II (temsirolimus, rituximab, bortezomib, dexamethasone)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (rituximab, bortezomib, dexamethasone); Arm II (temsirolimus, rituximab, bortezomib, dexamethasone)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm I (rituximab, bortezomib, dexamethasone); Arm II (temsirolimus, rituximab, bortezomib, dexamethasone)

Rituximab BIOLOGICAL

Given IV

Also known as: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab ABBS, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar JHL1101, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, Rituximab Biosimilar SIBP-02, rituximab biosimilar TQB2303, rituximab-abbs, RTXM83, Truxima

Arm I (rituximab, bortezomib, dexamethasone); Arm II (temsirolimus, rituximab, bortezomib, dexamethasone)

Temsirolimus DRUG

Given IV

Also known as: CCI-779, CCI-779 Rapamycin Analog, Cell Cycle Inhibitor 779, Rapamycin Analog, Rapamycin Analog CCI-779, Torisel

Arm II (temsirolimus, rituximab, bortezomib, dexamethasone)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 =\< 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (11)

Presbyterian - Saint Lukes Medical Center - Health One

Denver, Colorado, 80218, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

Location

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Gundersen Lutheran Medical Center

La Crosse, Wisconsin, 54601, United States

Location

Marshfield Medical Center-Marshfield

Marshfield, Wisconsin, 54449, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Marshfield Clinic-Minocqua Center

Minocqua, Wisconsin, 54548, United States

Location

MeSH Terms

Conditions

Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell; Waldenstrom Macroglobulinemia

Interventions

Bortezomib; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; Rituximab; CT-P10; temsirolimus; Sirolimus

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Macrolides; Lactones

Results Point of Contact

• Title: Study Statistician
• Organization: ECOG-ACRIN Biostatistics Center

eatrials@jimmy.harvard.edu

617-632-3012

Study Officials

• Leonard T Heffner

  ECOG-ACRIN Cancer Research Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2011
• First Posted: June 27, 2011
• Study Start: July 20, 2011
• Primary Completion: December 8, 2014
• Study Completion: September 1, 2021
• Last Updated: October 4, 2021
• Results First Posted: May 5, 2021

Record last verified: 2021-09

Locations

US (11)