A Randomized Phase I/II Study of Bortezomib, Rituximab, Dexamethasone and Temsirolimus in Patients With Relapsed Waldenstrom`s Macroglobulinemia and Relapsed/Refractory Mantle Cell, Follicular, Marginal Zone or Small Lymphocytic Lymphomas (Phase I), andUntreated/Relapsed Waldenstrom's Macroglobulinemia (Phase II)
PRIMARY OBJECTIVES:
I. 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:
I. 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 multicenter, phase I, dose-escalation study of temsirolimus followed by a
phase II study.
PHASE I: Patients receive temsirolimus 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 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 stratified according to disease status (previously untreated vs
relapsed) and by the International Prognostic Scoring System for Waldenstrom
macroglobulinemia staging (stage I or II vs stage III). Patients are randomized to 1 of 2
treatment arms.
ARM I: Patients receive rituximab intravenously (IV) over 30-60 minutes on days 1, 8, 15,
and 22 (of courses 1 and 4 only) and bortezomib IV and dexamethasone orally (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.
Patients complete the Functional Assessment of Cancer Therapy (FACT) Physical well-being
scale, the Functional well-being scale, and the FACT-Fatigue scale at baseline and
periodically during study.
After completion of study therapy, patients are followed up every 3 months for 2 years,
every 6 months for 5 years, and then yearly for 5 years.
Interventional
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD and recommended phase II dose of temsirolimus in combination with bortezomib, rituximab, and dexamethasone (Phase I)
Dose-limiting toxicity (DLT) is based on the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0).
Up to 6 courses
Yes
Leonard Heffner
Principal Investigator
Eastern Cooperative Oncology Group
United States: Food and Drug Administration
NCI-2011-02650
NCT01381692
July 2011
Name | Location |
---|---|
Mayo Clinic | Rochester, Minnesota 55905 |
Fox Chase Cancer Center | Philadelphia, Pennsylvania 19111 |
Geisinger Medical Center | Danville, Pennsylvania 17822-0001 |
Marshfield Clinic | Marshfield, Wisconsin 54449 |
Emory University | Atlanta, Georgia 30322 |
Presbyterian - Saint Lukes Medical Center - Health One | Denver, Colorado 80218 |
Marshfield Clinic-Minocqua Center | Minocqua, Wisconsin 54548 |
Gundersen Lutheran | La Crosse, Wisconsin 54601 |