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S1106 Rituximab With Combination Chemotherapy or Bendamustine Hydrochloride Followed by Consolidation Chemotherapy and Stem Cell Transplantation in Older Patients With Previously Untreated Mantle Cell Lymphoma

Sponsor
Southwest Oncology Group (Other)
Overall Status
Completed
CT.gov ID
NCT01412879
Collaborator
National Cancer Institute (NCI) (NIH)
53
Enrollment
204
Locations
2
Arms
112
Duration (Months)
0.3
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy also work in different ways to kill more cancer cells or stop them from growing. It is not yet known whether rituximab is more effective with combination chemotherapy or bendamustine hydrochloride in treating patients with mantle cell lymphoma undergoing peripheral blood stem cell transplantation.

PURPOSE: This randomized phase II trial studies how well giving rituximab together with combination chemotherapy or bendamustine hydrochloride followed by consolidation chemotherapy and peripheral blood stem cell transplantation works in treating older patients with previously untreated mantle cell lymphoma.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

OBJECTIVES:

  • To estimate the 2-year progression-free survival (PFS) of patients with newly diagnosed mantle cell lymphoma (MCL) treated with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, dexamethasone (RHCVAD), methotrexate and cytarabine (MTX/Ara-C), and autologous stem cell transplant (ASCT) or rituximab and bendamustine (R-bendamustine) and autologous stem cell transplant and to select a regimen for further development.

  • To assess the response rate and overall survival of patients with newly diagnosed MCL treated with R-HCVAD/MTX/Ara-C and ASCT or R-bendamustine and ASCT.

  • To assess the toxicity and tolerability of R-HCVAD/MTX/Ara-C and ASCT or R-bendamustine and ASCT in patients with newly diagnosed MCL.

  • To determine the prognostic value of quantitative minimal-residual disease (MRD) monitoring in the peripheral blood of MCL patients after induction therapy and serially after high-dose chemotherapy and ASCT on treatment outcome.

  • To bank diagnostic tissue sections for future translational research studies.

OUTLINE: This is a multicenter study. Patients are stratified according to risk classification by Mantle Cell Lymphoma International prognostic Index (MIPI) score (low risk vs intermediate/high risk). Patients are randomized to 1 of 2 treatment arms.

  • Arm I (induction therapy):

  • Courses 1 and 3: Patients receive induction therapy comprising rituximab IV on day 1; cyclophosphamide IV over 3 hours every 12 hours on days 2-4; doxorubicin hydrochloride IV over 72 hours on days 5-7; vincristine sulfate IV on days 5 and 12; and dexamethasone IV or orally (PO) once daily (QD) on days 2-5 and 12-15. Patients with responsive disease after course 1 proceed to course 2.

  • Course 2 and 4: Patients receive rituximab IV on day 1; methotrexate IV over 2-22 hours on day 2; cytarabine IV over 2 hours every 12 hours on days 3-4; and leucovorin calcium PO or IV on days 3-6. Patients undergo stem cell collection after completion of course 2.

  • Each course is 21 days long and continues in the absence of disease progression or unacceptable toxicity.

  • Arm II (induction therapy):

  • Course 1-6: Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1-2. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning 3-4 weeks later, patients with responsive disease receive 2 additional courses of treatment.

  • Stem cell mobilization: Beginning within 8 weeks, patients receive rituximab IV and cyclophosphamide IV over 1 hour on day 1. Patients then undergo stem cell collection about 26 days later.

Consolidation therapy: Patients receive one of the following preparative regimens.

  • BCV* chemotherapy: Carmustine IV over 2 hours on days -6 to -4; etoposide IV over 4 hours on day -4; and cyclophosphamide IV over 1 hour on day -2.

  • BEAM* chemotherapy: Carmustine IV over 4 hours on days -7 and -6; etoposide IV over 1 hour twice daily and cytarabine IV over 2 hours twice daily on days -5 to -2, and melphalan IV on day -1.

  • TBI, etoposide, cyclophosphamide: Patients undergo total-body irradiation (TBI)** twice daily on days -8 to -5. Patients also receive etoposide IV on day -4 and cyclophosphamide IV over 1 hour on day -2.

  • NOTE: * Patients 61 years of age or older receive either BCV or BEAM.

  • NOTE: * *TBI may not be used for patients 61 years of age and older. Stem cell transplantation: Patients then undergo autologous peripheral blood stem cell transplantation on day 0.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 2 years, and then annually for up to 8 years from registration.

Study Design

Study Type:
Interventional
Actual Enrollment :
53 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized Phase II Trial of R-HCVAD/MTX/ARA-C Induction Followed by Consolidation With an Autologous Stem Cell Transplant Vs. R-Bendamustine Induction Followed by Consolidation With an Autologous Stem Cell Transplant for Patients ≤ 65 Years of Age With Previously Untreated Mantle Cell Lymphoma
Study Start Date :
Nov 1, 2011
Actual Primary Completion Date :
Feb 1, 2016
Actual Study Completion Date :
Mar 1, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm I

Course 1 and 3: Patients receive induction therapy comprising rituximab IV on day 1; cyclophosphamide IV over 3 hours every 12 hours on days 2-4; doxorubicin hydrochloride IV over 72 hours on days 5-7; vincristine sulfate IV on days 5 and 12; and dexamethasone IV or orally (PO) once daily (QD) on days 2-5 and 12-15. Patients with responsive disease after course 1 proceed to course 2. Course 2 and 4: Patients receive rituximab IV on day 1; methotrexate IV over 2-22 hours on day 2; cytarabine IV over 2 hours every 12 hours on days 3-4; and leucovorin calcium PO or IV on days 3-6. Patients then undergo stem cell collection after completion of course 2. Patients undergo stem cell collection after completion of course 2.

Biological: rituximab
Given IV

Drug: cyclophosphamide
Given IV

Drug: cytarabine
Given IV

Drug: dexamethasone
Given PO or IV

Drug: doxorubicin hydrochloride
Given IV

Drug: leucovorin calcium
Given PO or IV

Drug: methotrexate
Given IV

Drug: vincristine sulfate
Given IV
Experimental: Arm II

Course 1-6: Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1-2. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning 3-4 weeks later, patients with responsive disease receive 2 additional courses of treatment. Beginning within 8 weeks, patients receive rituximab IV and cyclophosphamide IV over 1 hour on day 1. Patients then undergo stem cell collection about 26 days later.

Biological: rituximab
Given IV

Drug: bendamustine hydrochloride
Given IV

Drug: cyclophosphamide
Given IV

Outcome Measures

Primary Outcome Measures

  1. Progression-Free Survival (PFS) at 2 Years [Up to 2 years]

    Disease progression is defined using the 2007 revised Cheson et al. criteria that is at least 50% increase in sum of the product of the diameters (SPD) of target measurable nodal lesions over the smallest sum observed, or >= 50% increase in greatest transverse diameter (GTD) of any nodal > 1 cm in shortest axis, or >= 50% increase in the SPD of other target measurable lesions over the smallest sum observed, any new bone marrow involvement, any new lesion, lymph node with long axis is > 1.5 cm or if both long and short axes are > 1 cm, PET positive if patients with no pretreatment PET scan or when PET scan was positive before therapy. Progression-free survival is measured from date of registration to date of first observation of progressive disease, or death due to any cause. Patients last known to be alive and progression-free are censored at date of last contact.

Secondary Outcome Measures

  1. Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug [Up to 8 months (Assessed at the beginning of each cycle of treatment, at restaging, and at post transplant.)]

    Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.

  2. Response Rate (Complete and Partial Response) [Up to 9 months]

    Complete Response (CR) is a complete disappearance of all disease with the exception of the following. If no PET scan or when the PET scan was positive before therapy, a post-treatment residual mass of any size is permitted if it is PET negative. If the PET scan was negative before therapy, all nodal masses at baseline must have regressed. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow (BM) must be negative if positive at baseline. Normalization of markers. Partial Response (PR) is a 50% decrease in the sum of products of greatest diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes. If PET scan or when the PET scan was positive before therapy, PET should be positive in at least one previously involved site.

  3. 5-year Overall Survival (OS) [Up to 5 years]

    Measured from date of registration to date of death due to any cause. Patients last known to be alive and are censored at date of last contact.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
DISEASE CHARACTERISTICS:

  • All patients must have previously untreated stage III, IV, or bulky stage II mantle cell lymphoma (MCL)

  • A diagnosis of MCL must be confirmed by histopathological diagnosis including immunohistochemistry and flow cytometry documenting both of the following phenotypes:

  • CD19+ or CD20+

  • Cyclin D1+ or evidence of the t(11;14) translocation by cytogenetics or FISH

  • Adequate sections from the original diagnostic specimen must be available for submission for central review

  • An adequate biopsy requires sufficient tissue to establish the architecture and a WHO histologic subtype with certainty

  • Core biopsies, especially multiple core biopsies, MAY be adequate, but needle aspirations or cytologies are not adequate

  • Bone marrow core biopsy or clot sections (not aspirates) may be used as diagnostic material if it is significantly involved and are the only diagnostic material available

  • All patients must have bidimensional measurable disease documented on the Lymphoma Baseline Tumor Assessment Form (Form #48031)

  • Patients who also have non-measurable disease in addition to measurable disease must have all nonmeasurable disease assessed within 28 days prior to registration

  • Patients must not have clinical evidence of central nervous system (CNS) involvement by lymphoma

  • Any laboratory or radiographic tests performed prior to registration to assess CNS involvement must be negative

  • Patients must have a unilateral/bilateral bone marrow aspirate and biopsy for staging performed within 42 days prior to registration

  • If the biopsy cannot be performed but the aspirate is unequivocally consistent with mantle cell lymphoma, this will be considered adequate for staging purposes

  • Patients must be eligible for stem cell transplantation by institutional guidelines with the plan that transplant will be conducted at a cooperative group-approved transplant center

  • Patients must be planning to undergo stem cell transplantation within 84 days after day 1 of the last induction course

  • Patients must have had at least 1.5 X 106 CD34+ cells/kg collected and stored prior to second registration for stem cell transplantation

PATIENT CHARACTERISTICS:

  • Zubrod performance status of 0-2

  • Bilirubin ≤ 3 times upper limit of normal (ULN)

  • Serum creatinine ≤ 2.0 times ULN

  • Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 2.5 times ULN

  • Alkaline phosphatase ≤ 2.5 times ULN

  • Platelet count ≥ 100,000/mcL, unless due to bone marrow infiltration by lymphoma

  • All patients ≥ 45 years of age must have an echocardiogram (ECHO) or Multi Gated Acquisition Scan (MUGA )scan within 42 days prior to registration (whichever method is used at baseline must be used at restaging)

  • Patients < 45 years of age should have ECHO/MUGA only if clinically indicated

  • Patients with an ejection fraction < institutional lower limit of normal (ILLN) are not eligible

  • Serum Lactate dehydrogenase (LDH) and a Complete Blood Count (CBC with differential must be measured within 28 days prior to registration

  • Patients known to be HIV positive, or who have a history of solid organ transplantation, are ineligible

  • No active hepatitis

  • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer; in situ cervical cancer; adequately treated Stage I or II cancer from which the patient is currently in complete remission; or any other cancer from which the patient has been disease-free for 5 years

  • Pregnant or nursing women may not participate

  • Women or men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method

PRIOR CONCURRENT THERAPY:
  • See Disease Characteristics

Contacts and Locations

Locations

Site City State Country Postal Code
1 City of Hope Comprehensive Cancer Center Duarte California United States 91010-3000
2 Aurora Presbyterian Hospital Aurora Colorado United States 80012
3 Boulder Community Hospital Boulder Colorado United States 80301-9019
4 Penrose Cancer Center at Penrose Hospital Colorado Springs Colorado United States 80933
5 St. Anthony Central Hospital Denver Colorado United States 80204
6 Porter Adventist Hospital Denver Colorado United States 80210
7 Presbyterian - St. Luke's Medical Center Denver Colorado United States 80218
8 St. Joseph Hospital Denver Colorado United States 80218
9 Rose Medical Center Denver Colorado United States 80220
10 CCOP - Colorado Cancer Research Program Denver Colorado United States 80222
11 Swedish Medical Center Englewood Colorado United States 80110
12 North Colorado Medical Center Greeley Colorado United States 80631
13 Littleton Adventist Hospital Littleton Colorado United States 80122
14 Sky Ridge Medical Center Lone Tree Colorado United States 80124
15 Hope Cancer Care Center at Longmont United Hospital Longmont Colorado United States 80501
16 McKee Medical Center Loveland Colorado United States 80539
17 Parker Adventist Hospital Parker Colorado United States 80138
18 St. Mary - Corwin Regional Medical Center Pueblo Colorado United States 81004
19 Exempla Lutheran Medical Center Wheat Ridge Colorado United States 80033
20 Tunnell Cancer Center at Beebe Medical Center Lewes Delaware United States 19958
21 CCOP - Christiana Care Health Services Newark Delaware United States 19713
22 Florida Hospital Cancer Institute at Florida Hospital Orlando Orlando Florida United States 32803-1273
23 St. Joseph Regional Medical Center Lewiston Idaho United States 83501
24 Illinois CancerCare - Bloomington Bloomington Illinois United States 61701
25 Graham Hospital Canton Illinois United States 61520
26 Illinois CancerCare - Canton Canton Illinois United States 61520
27 Illinois CancerCare - Carthage Carthage Illinois United States 62321
28 Memorial Hospital Carthage Illinois United States 62321
29 Robert H. Lurie Comprehensive Cancer Center at Northwestern University Chicago Illinois United States 60611-3013
30 Hematology and Oncology Associates Chicago Illinois United States 60611
31 Decatur Memorial Hospital Cancer Care Institute Decatur Illinois United States 62526
32 Eureka Community Hospital Eureka Illinois United States 61530
33 Illinois CancerCare - Eureka Eureka Illinois United States 61530
34 Galesburg Clinic, PC Galesburg Illinois United States 61401
35 Illinois CancerCare - Galesburg Galesburg Illinois United States 61401
36 Illinois CancerCare - Havana Havana Illinois United States 62644
37 Mason District Hospital Havana Illinois United States 62644
38 Kellogg Cancer Care Center Highland Park Illinois United States 60035
39 Provena St. Mary's Regional Cancer Center - Kankakee Kankakee Illinois United States 60901
40 Illinois CancerCare - Kewanee Clinic Kewanee Illinois United States 61443
41 North Shore Oncology and Hematology Associates, Limited - Libertyville Libertyville Illinois United States 60048
42 Illinois CancerCare - Macomb Macomb Illinois United States 61455
43 McDonough District Hospital Macomb Illinois United States 61455
44 Cardinal Bernardin Cancer Center at Loyola University Medical Center Maywood Illinois United States 60153
45 Illinois CancerCare - Monmouth Monmouth Illinois United States 61462
46 Cancer Care and Hematology Specialists of Chicagoland - Niles Niles Illinois United States 60714
47 BroMenn Regional Medical Center Normal Illinois United States 61761
48 Community Cancer Center Normal Illinois United States 61761
49 Illinois CancerCare - Community Cancer Center Normal Illinois United States 61761
50 Community Hospital of Ottawa Ottawa Illinois United States 61350
51 Oncology Hematology Associates of Central Illinois, PC - Ottawa Ottawa Illinois United States 61350
52 Cancer Treatment Center at Pekin Hospital Pekin Illinois United States 61554
53 Illinois CancerCare - Pekin Pekin Illinois United States 61603
54 Proctor Hospital Peoria Illinois United States 61614
55 CCOP - Illinois Oncology Research Association Peoria Illinois United States 61615
56 Oncology Hematology Associates of Central Illinois, PC - Peoria Peoria Illinois United States 61615
57 Methodist Medical Center of Illinois Peoria Illinois United States 61636
58 Illinois CancerCare - Peru Peru Illinois United States 61354
59 Illinois Valley Community Hospital Peru Illinois United States 61354
60 Illinois CancerCare - Princeton Princeton Illinois United States 61356
61 Perry Memorial Hospital Princeton Illinois United States 61356
62 Hematology Oncology Associates - Skokie Skokie Illinois United States 60076
63 Illinois CancerCare - Spring Valley Spring Valley Illinois United States 61362
64 Regional Cancer Center at Memorial Medical Center Springfield Illinois United States 62781-0001
65 St. Francis Hospital and Health Centers - Beech Grove Campus Beech Grove Indiana United States 46107
66 Reid Hospital & Health Care Services Richmond Indiana United States 47374
67 McFarland Clinic, PC Ames Iowa United States 50010
68 Siouxland Hematology-Oncology Associates, LLP Sioux City Iowa United States 51101
69 Mercy Medical Center - Sioux City Sioux City Iowa United States 51102
70 St. Luke's Regional Medical Center Sioux City Iowa United States 51104
71 Cancer Center of Kansas, PA - Chanute Chanute Kansas United States 66720
72 Cancer Center of Kansas, PA - Dodge City Dodge City Kansas United States 67801
73 Cancer Center of Kansas, PA - El Dorado El Dorado Kansas United States 67042
74 Cancer Center of Kansas - Fort Scott Fort Scott Kansas United States 66701
75 Cancer Center of Kansas-Independence Independence Kansas United States 67301
76 Cancer Center of Kansas, PA - Kingman Kingman Kansas United States 67068
77 Lawrence Memorial Hospital Lawrence Kansas United States 66044
78 Cancer Center of Kansas, PA - Liberal Liberal Kansas United States 67901
79 Cancer Center of Kansas, PA - McPherson McPherson Kansas United States 67460
80 Cancer Center of Kansas, PA - Newton Newton Kansas United States 67114
81 Cancer Center of Kansas, PA - Parsons Parsons Kansas United States 67357
82 Cancer Center of Kansas, PA - Pratt Pratt Kansas United States 67124
83 Cancer Center of Kansas, PA - Salina Salina Kansas United States 67401
84 Cancer Center of Kansas, PA - Wellington Wellington Kansas United States 67152
85 Associates in Womens Health, PA - North Review Wichita Kansas United States 67208
86 Cancer Center of Kansas, PA - Medical Arts Tower Wichita Kansas United States 67208
87 Cancer Center of Kansas, PA - Wichita Wichita Kansas United States 67214
88 CCOP - Wichita Wichita Kansas United States 67214
89 Via Christi Cancer Center at Via Christi Regional Medical Center Wichita Kansas United States 67214
90 Cancer Center of Kansas, PA - Winfield Winfield Kansas United States 67156
91 Lucille P. Markey Cancer Center at University of Kentucky Lexington Kentucky United States 40536-0093
92 Union Hospital of Cecil County Elkton Maryland United States 21921
93 Hickman Cancer Center at Bixby Medical Center Adrian Michigan United States 49221
94 Barbara Ann Karmanos Cancer Institute Detroit Michigan United States 48201-1379
95 Mercy Memorial Hospital - Monroe Monroe Michigan United States 48162
96 Fairview Ridges Hospital Burnsville Minnesota United States 55337
97 Mercy and Unity Cancer Center at Mercy Hospital Coon Rapids Minnesota United States 55433
98 Fairview Southdale Hospital Edina Minnesota United States 55435
99 Mercy and Unity Cancer Center at Unity Hospital Fridley Minnesota United States 55432
100 Hutchinson Area Health Care Hutchinson Minnesota United States 55350
101 HealthEast Cancer Care at St. John's Hospital Maplewood Minnesota United States 55109
102 Minnesota Oncology - Maplewood Maplewood Minnesota United States 55109
103 Virginia Piper Cancer Institute at Abbott - Northwestern Hospital Minneapolis Minnesota United States 55407
104 Hennepin County Medical Center - Minneapolis Minneapolis Minnesota United States 55415
105 New Ulm Medical Center New Ulm Minnesota United States 56073
106 Humphrey Cancer Center at North Memorial Outpatient Center Robbinsdale Minnesota United States 55422-2900
107 CCOP - Metro-Minnesota Saint Louis Park Minnesota United States 55416
108 Park Nicollet Cancer Center Saint Louis Park Minnesota United States 55416
109 Regions Hospital Cancer Care Center Saint Paul Minnesota United States 55101
110 United Hospital Saint Paul Minnesota United States 55102
111 St. Francis Cancer Center at St. Francis Medical Center Shakopee Minnesota United States 55379
112 Lakeview Hospital Stillwater Minnesota United States 55082
113 Ridgeview Medical Center Waconia Minnesota United States 55387
114 Willmar Cancer Center at Rice Memorial Hospital Willmar Minnesota United States 56201
115 Minnesota Oncology - Woodbury Woodbury Minnesota United States 55125
116 Saint Louis University Cancer Center Saint Louis Missouri United States 63110
117 Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis Saint Louis Missouri United States 63110
118 Cancer Institute of New Jersey at Hamilton Hamilton New Jersey United States 08690
119 Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School New Brunswick New Jersey United States 08903
120 Cancer Institute of New Jersey at Cooper - Voorhees Voorhees New Jersey United States 08043
121 James P. Wilmot Cancer Center at University of Rochester Medical Center Rochester New York United States 14642
122 SUNY Upstate Medical University Hospital Syracuse New York United States 13210
123 Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center Columbus Ohio United States 43210-1240
124 Grandview Hospital Dayton Ohio United States 45405
125 Good Samaritan Hospital Dayton Ohio United States 45406
126 David L. Rike Cancer Center at Miami Valley Hospital Dayton Ohio United States 45409
127 Samaritan North Cancer Care Center Dayton Ohio United States 45415
128 CCOP - Dayton Dayton Ohio United States 45420
129 Community Cancer Center Elyria Ohio United States 44035
130 Hematology Oncology Center Elyria Ohio United States 44035
131 Blanchard Valley Medical Associates Findlay Ohio United States 45840
132 Middletown Regional Hospital Franklin Ohio United States 45005-1066
133 Wayne Hospital Greenville Ohio United States 45331
134 Charles F. Kettering Memorial Hospital Kettering Ohio United States 45429
135 Lima Memorial Hospital Lima Ohio United States 45804
136 Northwest Ohio Oncology Center Maumee Ohio United States 43537-1839
137 St. Charles Mercy Hospital Oregon Ohio United States 43616
138 North Coast Cancer Care, Incorporated Sandusky Ohio United States 44870
139 Flower Hospital Cancer Center Sylvania Ohio United States 43560
140 Mercy Hospital of Tiffin Tiffin Ohio United States 44883
141 Toledo Hospital Toledo Ohio United States 43606
142 St. Vincent Mercy Medical Center Toledo Ohio United States 43608
143 Medical University of Ohio Cancer Center Toledo Ohio United States 43614
144 CCOP - Toledo Community Hospital Toledo Ohio United States 43617
145 St. Anne Mercy Hospital Toledo Ohio United States 43623
146 Toledo Clinic, Incorporated - Main Clinic Toledo Ohio United States 43623
147 UVMC Cancer Care Center at Upper Valley Medical Center Troy Ohio United States 45373-1300
148 Fulton County Health Center Wauseon Ohio United States 43567
149 Ruth G. McMillan Cancer Center at Greene Memorial Hospital Xenia Ohio United States 45385
150 Clackamas Radiation Oncology Center Clackamas Oregon United States 97015
151 Providence Milwaukie Hospital Milwaukie Oregon United States 97222
152 Providence Newberg Medical Center Newberg Oregon United States 97132
153 Willamette Falls Hospital Oregon City Oregon United States 97045
154 Providence Cancer Center at Providence Portland Medical Center Portland Oregon United States 97213-2967
155 CCOP - Columbia River Oncology Program Portland Oregon United States 97225
156 Providence St. Vincent Medical Center Portland Oregon United States 97225
157 Geisinger Cancer Institute at Geisinger Health Danville Pennsylvania United States 17822-0001
158 Geisinger Hazleton Cancer Center Hazleton Pennsylvania United States 18201
159 Geisinger Medical Group - Scenery Park State College Pennsylvania United States 16801
160 Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center Wilkes-Barre Pennsylvania United States 18711
161 Cancer Centers of the Carolinas - Faris Road Greenville South Carolina United States 29605
162 Cancer Centers of the Carolinas - Grove Commons Greenville South Carolina United States 29605
163 Greenville Hospital Cancer Center Greenville South Carolina United States 29605
164 CCOP - Greenville Greenville South Carolina United States 29615
165 Cancer Centers of the Carolinas - Greer Medical Oncology Greer South Carolina United States 29650
166 Cancer Centers of the Carolinas - Seneca Seneca South Carolina United States 29672
167 Cancer Centers of the Carolinas - Spartanburg Spartanburg South Carolina United States 29307
168 Baylor University Medical Center - Dallas Dallas Texas United States 75246
169 Fredericksburg Oncology, Incorporated Fredericksburg Virginia United States 22401
170 Island Hospital Cancer Care Center at Island Hospital Anacortes Washington United States 98221
171 Overlake Cancer Center at Overlake Hospital Medical Center Bellevue Washington United States 98004
172 St. Joseph Cancer Center Bellingham Washington United States 98225
173 Olympic Hematology and Oncology Bremerton Washington United States 98310
174 Highline Medical Center Cancer Center Burien Washington United States 98166
175 Providence Centralia Hospital Centralia Washington United States 98531-9027
176 Providence Regional Cancer Partnership Everett Washington United States 98201
177 St. Francis Hospital Federal Way Washington United States 98003
178 Swedish Medical Center - Issaquah Campus Issaquah Washington United States 98029
179 Columbia Basin Hematology Kennewick Washington United States 99336
180 Skagit Valley Hospital Cancer Care Center Mount Vernon Washington United States 98274
181 Providence St. Peter Hospital Regional Cancer Center Olympia Washington United States 98506-5166
182 Harrison Poulsbo Hematology and Onocology Poulsbo Washington United States 98370
183 Good Samaritan Cancer Center Puyallup Washington United States 98372
184 Harborview Medical Center Seattle Washington United States 98104
185 Minor and James Medical, PLLC Seattle Washington United States 98104
186 Fred Hutchinson Cancer Research Center Seattle Washington United States 98109
187 Group Health Central Hospital Seattle Washington United States 98112
188 Swedish Cancer Institute at Swedish Medical Center - First Hill Campus Seattle Washington United States 98122-4307
189 Polyclinic First Hill Seattle Washington United States 98122
190 University Cancer Center at University of Washington Medical Center Seattle Washington United States 98195
191 North Puget Oncology at United General Hospital Sedro-Woolley Washington United States 98284
192 Cancer Care Northwest - Spokane South Spokane Washington United States 99202
193 Evergreen Hematology and Oncology, PS Spokane Washington United States 99218
194 Franciscan Cancer Center at St. Joseph Medical Center Tacoma Washington United States 98405-3004
195 Allenmore Hospital Tacoma Washington United States 98405
196 CCOP - Northwest Tacoma Washington United States 98405
197 MultiCare Regional Cancer Center at Tacoma General Hospital Tacoma Washington United States 98405
198 St. Clare Hospital Tacoma Washington United States 98499
199 Southwest Washington Medical Center Cancer Center Vancouver Washington United States 98664
200 Northwest Cancer Specialists at Vancouver Cancer Center Vancouver Washington United States 98684
201 Wenatchee Valley Medical Center Wenatchee Washington United States 98801-2028
202 Mary Babb Randolph Cancer Center at West Virginia University Hospitals Morgantown West Virginia United States 26506
203 Gundersen Lutheran Center for Cancer and Blood La Crosse Wisconsin United States 54601
204 Medical College of Wisconsin Cancer Center Milwaukee Wisconsin United States 53226

Sponsors and Collaborators

  • Southwest Oncology Group
  • National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Steven H. Bernstein, MD, James P. Wilmot Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT01412879
Other Study ID Numbers:
  • CDR0000707601
  • S1106
  • U10CA032102
First Posted:
Aug 9, 2011
Last Update Posted:
Oct 29, 2021
Last Verified:
Oct 1, 2021
Keywords provided by Southwest Oncology Group
contiguous stage II mantle cell lymphoma
noncontiguous stage II mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Leucovorin
Cytarabine
Dexamethasone
Cyclophosphamide
Bendamustine Hydrochloride
Rituximab
Doxorubicin
Liposomal doxorubicin
Methotrexate
Vincristine
Levoleucovorin

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Arm 1: R-HCVAD/MTX/Ara-C (Induction Therapy) Arm 2: R-Bendamustine (Induction Therapy) Consolidation Therapy: Stem Cell Transplant
Arm/Group Description The R-HCVAD/MTX/ARA-C combination are rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine. Cycle 1 and 3: Patients receive induction therapy comprising rituximab IV on day 1; cyclophosphamide IV over 3 hours every 12 hours on days 2-4; doxorubicin hydrochloride IV over 72 hours on days 5-7; vincristine sulfate IV on days 5 and 12; and dexamethasone IV or orally (PO) once daily (QD) on days 2-5 and 12-15. Patients with responsive disease after course 1 proceed to course 2. Cycle 2 and 4: Patients receive rituximab IV on day 1; methotrexate IV over 2-22 hours on day 2; cytarabine IV over 2 hours every 12 hours on days 3-4; and leucovorin calcium PO or IV on days 3-6. Patients undergo stem cell collection after completion of Cycle 2 (1 cycle = 21 days). R-bendamustine combinations are rituximab and bendamustine. Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1-2. Treatment repeats every 28 days for 4 cycles (1 cycle = 28 days). Patients with responsive disease receive 2 additional cycles of treatment. Patients undergo stem cell collection after completion of 6 Cycles of treatment. Patients receive stem cell transplant with non-TBI containing regimen (BCV or BEAM Chemotherapy) for patients 61 years or older or TBI-containing regimen (TBI/VP-16/Cyclophosphamide). BCV chemotherapy: Carmustine IV over 2 hours on days -6 to -4; etoposide IV over 4 hours on day -4; and cyclophosphamide IV over 1 hour on day -2. BEAM chemotherapy: Carmustine IV over 4 hours on days -7 and -6; etoposide IV over 1 hour twice daily and cytarabine IV over 2 hours twice daily on days -5 to -2, and melphalan IV on day -1. TBI, etoposide, cyclophosphamide: Patients undergo total-body irradiation (TBI)** twice daily on days -8 to -5. Patients also receive etoposide IV on day -4 and cyclophosphamide IV over 1 hour on day -2. * *TBI may not be used for patients 61 years of age and older. Stem cell transplantation: Patients then undergo autologous peripheral blood stem cell transplantation on day 0.
Period Title: Initial Registration (Induction Therapy)
STARTED 18 35 0
Treatment Started 17 35 0
COMPLETED 5 27 0
NOT COMPLETED 13 8 0
Period Title: Initial Registration (Induction Therapy)
STARTED 0 0 26
COMPLETED 0 0 26
NOT COMPLETED 0 0 0

Baseline Characteristics

Arm/Group Title Arm 1: R-HCVAD/MTX/Ara-C (Induction Therapy) Arm 2: R-Bendamustine (Induction Therapy) Total
Arm/Group Description The R-HCVAD/MTX/ARA-C combination are rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine. Cycle 1 and 3: Patients receive induction therapy comprising rituximab IV on day 1; cyclophosphamide IV over 3 hours every 12 hours on days 2-4; doxorubicin hydrochloride IV over 72 hours on days 5-7; vincristine sulfate IV on days 5 and 12; and dexamethasone IV or orally (PO) once daily (QD) on days 2-5 and 12-15. Patients with responsive disease after course 1 proceed to course 2. Cycle 2 and 4: Patients receive rituximab IV on day 1; methotrexate IV over 2-22 hours on day 2; cytarabine IV over 2 hours every 12 hours on days 3-4; and leucovorin calcium PO or IV on days 3-6. Patients undergo stem cell collection after completion of Cycle 2 (1 cycle = 21 days). R-bendamustine combinations are rituximab and bendamustine. Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1-2. Treatment repeats every 28 days for 4 cycles (1 cycle = 28 days). Patients with responsive disease receive 2 additional cycles of treatment. Patients undergo stem cell collection after completion of 6 Cycles of treatment. Total of all reporting groups
Overall Participants 17 35 52
Age (years) [Median (Full Range) ]
Median (Full Range) [years]
58.8
56.6
57.2
Sex: Female, Male (Count of Participants)
Female
8
47.1%
3
8.6%
11
21.2%
Male
9
52.9%
32
91.4%
41
78.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
0
0%
0
0%
0
0%
Not Hispanic or Latino
16
94.1%
35
100%
51
98.1%
Unknown or Not Reported
1
5.9%
0
0%
1
1.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
Asian
1
5.9%
0
0%
1
1.9%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
Black or African American
1
5.9%
2
5.7%
3
5.8%
White
13
76.5%
32
91.4%
45
86.5%
More than one race
0
0%
0
0%
0
0%
Unknown or Not Reported
2
11.8%
1
2.9%
3
5.8%

Outcome Measures

1. Primary Outcome
Title Progression-Free Survival (PFS) at 2 Years
Description Disease progression is defined using the 2007 revised Cheson et al. criteria that is at least 50% increase in sum of the product of the diameters (SPD) of target measurable nodal lesions over the smallest sum observed, or >= 50% increase in greatest transverse diameter (GTD) of any nodal > 1 cm in shortest axis, or >= 50% increase in the SPD of other target measurable lesions over the smallest sum observed, any new bone marrow involvement, any new lesion, lymph node with long axis is > 1.5 cm or if both long and short axes are > 1 cm, PET positive if patients with no pretreatment PET scan or when PET scan was positive before therapy. Progression-free survival is measured from date of registration to date of first observation of progressive disease, or death due to any cause. Patients last known to be alive and progression-free are censored at date of last contact.
Time Frame Up to 2 years

Outcome Measure Data

Analysis Population Description
All eligible patients who started treatment were included in the analysis
Arm/Group Title Arm 1: R-HCVAD/MTX/Ara-C (Induction Therapy) Arm 2: R-Bendamustine (Induction Therapy)
Arm/Group Description The R-HCVAD/MTX/ARA-C combination are rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine. Cycle 1 and 3: Patients receive induction therapy comprising rituximab IV on day 1; cyclophosphamide IV over 3 hours every 12 hours on days 2-4; doxorubicin hydrochloride IV over 72 hours on days 5-7; vincristine sulfate IV on days 5 and 12; and dexamethasone IV or orally (PO) once daily (QD) on days 2-5 and 12-15. Patients with responsive disease after course 1 proceed to course 2. Cycle 2 and 4: Patients receive rituximab IV on day 1; methotrexate IV over 2-22 hours on day 2; cytarabine IV over 2 hours every 12 hours on days 3-4; and leucovorin calcium PO or IV on days 3-6. Patients undergo stem cell collection after completion of Cycle 2 (1 cycle = 21 days). R-bendamustine combinations are rituximab and bendamustine. Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1-2. Treatment repeats every 28 days for 4 cycles (1 cycle = 28 days). Patients with responsive disease receive 2 additional cycles of treatment. Patients undergo stem cell collection after completion of 6 Cycles of treatment.
Measure Participants 17 35
Number (95% Confidence Interval) [percentage of participants]
82
482.4%
81
231.4%
2. Secondary Outcome
Title Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug
Description Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.
Time Frame Up to 8 months (Assessed at the beginning of each cycle of treatment, at restaging, and at post transplant.)

Outcome Measure Data

Analysis Population Description
Eligible patients who had received any treatment were included in the adverse event summaries. Any CTCAE 4.0 event of Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal) which deemed to be related to protocol treatment are included.
Arm/Group Title R-HCVAD/MTX/Ara-C (Induction Therapy) R-Bendamustine (Induction Therapy) Stem Cell Transplant (Consolidation Therapy)
Arm/Group Description The R-HCVAD/MTX/ARA-C combination are rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine. Cycle 1 and 3: Patients receive induction therapy comprising rituximab IV on day 1; cyclophosphamide IV over 3 hours every 12 hours on days 2-4; doxorubicin hydrochloride IV over 72 hours on days 5-7; vincristine sulfate IV on days 5 and 12; and dexamethasone IV or orally (PO) once daily (QD) on days 2-5 and 12-15. Patients with responsive disease after course 1 proceed to course 2. Cycle 2 and 4: Patients receive rituximab IV on day 1; methotrexate IV over 2-22 hours on day 2; cytarabine IV over 2 hours every 12 hours on days 3-4; and leucovorin calcium PO or IV on days 3-6. Patients undergo stem cell collection after completion of Cycle 2 (1 cycle = 21 days). R-bendamustine combinations are rituximab and bendamustine. Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1-2. Treatment repeats every 28 days for 4 cycles (1 cycle = 28 days). Patients with responsive disease receive 2 additional cycles of treatment. Patients undergo stem cell collection after completion of 6 Cycles of treatment. Patients receive stem cell transplant with non-TBI containing regimen (BCV or BEAM Chemotherapy) for patients 61 years or older or TBI-containing regimen (TBI/VP-16/Cyclophosphamide). BCV chemotherapy: Carmustine IV over 2 hours on days -6 to -4; etoposide IV over 4 hours on day -4; and cyclophosphamide IV over 1 hour on day -2. BEAM chemotherapy: Carmustine IV over 4 hours on days -7 and -6; etoposide IV over 1 hour twice daily and cytarabine IV over 2 hours twice daily on days -5 to -2, and melphalan IV on day -1. TBI, etoposide, cyclophosphamide: Patients undergo total-body irradiation (TBI)** twice daily on days -8 to -5. Patients also receive etoposide IV on day -4 and cyclophosphamide IV over 1 hour on day -2. * *TBI may not be used for patients 61 years of age and older. Stem cell transplantation: Patients then undergo autologous peripheral blood stem cell transplantation on day 0.
Measure Participants 17 35 26
Acidosis
0
0%
0
0%
1
1.9%
Adult respiratory distress syndrome
0
0%
0
0%
1
1.9%
Alanine aminotransferase increased
1
5.9%
0
0%
0
0%
Anemia
10
58.8%
3
8.6%
9
17.3%
Anorexia
0
0%
0
0%
1
1.9%
Arthralgia
0
0%
1
2.9%
0
0%
Aspartate aminotransferase increased
1
5.9%
0
0%
0
0%
Blood bilirubin increased
0
0%
0
0%
2
3.8%
CD4 lymphocytes decreased
2
11.8%
2
5.7%
0
0%
Catheter related infection
1
5.9%
1
2.9%
1
1.9%
Dehydration
1
5.9%
0
0%
0
0%
Device related infection
0
0%
0
0%
1
1.9%
Diarrhea
1
5.9%
0
0%
4
7.7%
Enterocolitis
0
0%
0
0%
1
1.9%
Enterocolitis infectious
0
0%
1
2.9%
1
1.9%
Epistaxis
1
5.9%
0
0%
0
0%
Fatigue
0
0%
1
2.9%
0
0%
Febrile neutropenia
5
29.4%
5
14.3%
13
25%
Gallbladder infection
0
0%
0
0%
1
1.9%
Hyperglycemia
2
11.8%
0
0%
0
0%
Hypoalbuminemia
0
0%
1
2.9%
0
0%
Hypocalcemia
0
0%
0
0%
2
3.8%
Hypokalemia
5
29.4%
2
5.7%
1
1.9%
Hypomagnesemia
0
0%
0
0%
1
1.9%
Hyponatremia
0
0%
0
0%
1
1.9%
Hypophosphatemia
4
23.5%
1
2.9%
3
5.8%
Hypotension
0
0%
0
0%
1
1.9%
Hypoxia
0
0%
0
0%
1
1.9%
Infections and infestations - Other, specify
0
0%
1
2.9%
0
0%
Infusion related reaction
0
0%
1
2.9%
0
0%
Lung infection
0
0%
0
0%
1
1.9%
Lymphocyte count decreased
10
58.8%
27
77.1%
12
23.1%
Myalgia
0
0%
1
2.9%
0
0%
Nausea
1
5.9%
0
0%
2
3.8%
Neutrophil count decreased
11
64.7%
12
34.3%
16
30.8%
Pain in extremity
0
0%
1
2.9%
0
0%
Platelet count decreased
12
70.6%
6
17.1%
19
36.5%
Pruritus
0
0%
1
2.9%
0
0%
Rash maculo-papular
1
5.9%
1
2.9%
1
1.9%
Rectal hemorrhage
0
0%
0
0%
1
1.9%
Small intestinal obstruction
0
0%
0
0%
1
1.9%
Sore throat
0
0%
1
2.9%
0
0%
Syncope
1
5.9%
0
0%
0
0%
Tumor pain
0
0%
1
2.9%
0
0%
Urinary tract infection
0
0%
1
2.9%
0
0%
Vascular access complication
0
0%
1
2.9%
0
0%
Vomiting
0
0%
0
0%
1
1.9%
White blood cell decreased
10
58.8%
14
40%
20
38.5%
3. Secondary Outcome
Title Response Rate (Complete and Partial Response)
Description Complete Response (CR) is a complete disappearance of all disease with the exception of the following. If no PET scan or when the PET scan was positive before therapy, a post-treatment residual mass of any size is permitted if it is PET negative. If the PET scan was negative before therapy, all nodal masses at baseline must have regressed. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow (BM) must be negative if positive at baseline. Normalization of markers. Partial Response (PR) is a 50% decrease in the sum of products of greatest diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes. If PET scan or when the PET scan was positive before therapy, PET should be positive in at least one previously involved site.
Time Frame Up to 9 months

Outcome Measure Data

Analysis Population Description
All eligible patients who started treatment were included in the analysis.
Arm/Group Title Arm 1: R-HCVAD/MTX/Ara-C (Induction Therapy) Arm 2: R-Bendamustine (Induction Therapy)
Arm/Group Description The R-HCVAD/MTX/ARA-C combination are rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine. Cycle 1 and 3: Patients receive induction therapy comprising rituximab IV on day 1; cyclophosphamide IV over 3 hours every 12 hours on days 2-4; doxorubicin hydrochloride IV over 72 hours on days 5-7; vincristine sulfate IV on days 5 and 12; and dexamethasone IV or orally (PO) once daily (QD) on days 2-5 and 12-15. Patients with responsive disease after course 1 proceed to course 2. Cycle 2 and 4: Patients receive rituximab IV on day 1; methotrexate IV over 2-22 hours on day 2; cytarabine IV over 2 hours every 12 hours on days 3-4; and leucovorin calcium PO or IV on days 3-6. Patients undergo stem cell collection after completion of Cycle 2 (1 cycle = 21 days). R-bendamustine combinations are rituximab and bendamustine. Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1-2. Treatment repeats every 28 days for 4 cycles (1 cycle = 28 days). Patients with responsive disease receive 2 additional cycles of treatment. Patients undergo stem cell collection after completion of 6 Cycles of treatment.
Measure Participants 17 35
Number (95% Confidence Interval) [percentage of participants]
94.1
553.5%
82.9
236.9%
4. Secondary Outcome
Title 5-year Overall Survival (OS)
Description Measured from date of registration to date of death due to any cause. Patients last known to be alive and are censored at date of last contact.
Time Frame Up to 5 years

Outcome Measure Data

Analysis Population Description
All eligible patients who started treatment were included in the analysis.
Arm/Group Title Arm 1: R-HCVAD/MTX/Ara-C (Induction Therapy) Arm 2: R-Bendamustine (Induction Therapy)
Arm/Group Description The R-HCVAD/MTX/ARA-C combination are rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine. Cycle 1 and 3: Patients receive induction therapy comprising rituximab IV on day 1; cyclophosphamide IV over 3 hours every 12 hours on days 2-4; doxorubicin hydrochloride IV over 72 hours on days 5-7; vincristine sulfate IV on days 5 and 12; and dexamethasone IV or orally (PO) once daily (QD) on days 2-5 and 12-15. Patients with responsive disease after course 1 proceed to course 2. Cycle 2 and 4: Patients receive rituximab IV on day 1; methotrexate IV over 2-22 hours on day 2; cytarabine IV over 2 hours every 12 hours on days 3-4; and leucovorin calcium PO or IV on days 3-6. Patients undergo stem cell collection after completion of Cycle 2 (1 cycle = 21 days). R-bendamustine combinations are rituximab and bendamustine. Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1-2. Treatment repeats every 28 days for 4 cycles (1 cycle = 28 days). Patients with responsive disease receive 2 additional cycles of treatment. Patients undergo stem cell collection after completion of 6 Cycles of treatment.
Measure Participants 17 35
Number (95% Confidence Interval) [percentage of participants]
81
476.5%
79
225.7%

Adverse Events

Time Frame Up to 8 months (assessed at the beginning of each cycle of treatment, at restaging, and at post transplant).
Adverse Event Reporting Description
Arm/Group Title R-HCVAD/MTX/Ara-C (Induction Therapy) R-Bendamustine (Induction Therapy) Stem Cell Transplant (Consolidation Therapy)
Arm/Group Description The R-HCVAD/MTX/ARA-C combination are rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine. Cycle 1 and 3: Patients receive induction therapy comprising rituximab IV on day 1; cyclophosphamide IV over 3 hours every 12 hours on days 2-4; doxorubicin hydrochloride IV over 72 hours on days 5-7; vincristine sulfate IV on days 5 and 12; and dexamethasone IV or orally (PO) once daily (QD) on days 2-5 and 12-15. Patients with responsive disease after course 1 proceed to course 2. Cycle 2 and 4: Patients receive rituximab IV on day 1; methotrexate IV over 2-22 hours on day 2; cytarabine IV over 2 hours every 12 hours on days 3-4; and leucovorin calcium PO or IV on days 3-6. Patients undergo stem cell collection after completion of Cycle 2 (1 cycle = 21 days). R-bendamustine combinations are rituximab and bendamustine. Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1-2. Treatment repeats every 28 days for 4 cycles (1 cycle = 28 days). Patients with responsive disease receive 2 additional cycles of treatment. Patients undergo stem cell collection after completion of 6 Cycles of treatment. Patients receive stem cell transplant with non-TBI containing regimen (BCV or BEAM Chemotherapy) for patients 61 years or older or TBI-containing regimen (TBI/VP-16/Cyclophosphamide). BCV chemotherapy: Carmustine IV over 2 hours on days -6 to -4; etoposide IV over 4 hours on day -4; and cyclophosphamide IV over 1 hour on day -2. BEAM chemotherapy: Carmustine IV over 4 hours on days -7 and -6; etoposide IV over 1 hour twice daily and cytarabine IV over 2 hours twice daily on days -5 to -2, and melphalan IV on day -1. TBI, etoposide, cyclophosphamide: Patients undergo total-body irradiation (TBI)** twice daily on days -8 to -5. Patients also receive etoposide IV on day -4 and cyclophosphamide IV over 1 hour on day -2. * *TBI may not be used for patients 61 years of age and older. Stem cell transplantation: Patients then undergo autologous peripheral blood stem cell transplantation on day 0.
All Cause Mortality
R-HCVAD/MTX/Ara-C (Induction Therapy) R-Bendamustine (Induction Therapy) Stem Cell Transplant (Consolidation Therapy)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN) / (NaN)
Serious Adverse Events
R-HCVAD/MTX/Ara-C (Induction Therapy) R-Bendamustine (Induction Therapy) Stem Cell Transplant (Consolidation Therapy)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/17 (0%) 0/35 (0%) 1/26 (3.8%)
Gastrointestinal disorders
Diarrhea 0/17 (0%) 0/35 (0%) 1/26 (3.8%)
Infections and infestations
Enterocolitis infectious 0/17 (0%) 0/35 (0%) 1/26 (3.8%)
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome 0/17 (0%) 0/35 (0%) 1/26 (3.8%)
Other (Not Including Serious) Adverse Events
R-HCVAD/MTX/Ara-C (Induction Therapy) R-Bendamustine (Induction Therapy) Stem Cell Transplant (Consolidation Therapy)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 17/17 (100%) 35/35 (100%) 26/26 (100%)
Blood and lymphatic system disorders
Anemia 15/17 (88.2%) 25/35 (71.4%) 21/26 (80.8%)
Febrile neutropenia 5/17 (29.4%) 5/35 (14.3%) 13/26 (50%)
Cardiac disorders
Pericardial effusion 1/17 (5.9%) 0/35 (0%) 0/26 (0%)
Sinus bradycardia 1/17 (5.9%) 3/35 (8.6%) 1/26 (3.8%)
Sinus tachycardia 3/17 (17.6%) 3/35 (8.6%) 2/26 (7.7%)
Ear and labyrinth disorders
Ear pain 1/17 (5.9%) 0/35 (0%) 0/26 (0%)
Tinnitus 1/17 (5.9%) 0/35 (0%) 0/26 (0%)
Eye disorders
Blurred vision 0/17 (0%) 3/35 (8.6%) 1/26 (3.8%)
Conjunctivitis 1/17 (5.9%) 0/35 (0%) 0/26 (0%)
Dry eye 1/17 (5.9%) 0/35 (0%) 0/26 (0%)
Watering eyes 0/17 (0%) 0/35 (0%) 2/26 (7.7%)
Gastrointestinal disorders
Abdominal distension 0/17 (0%) 2/35 (5.7%) 1/26 (3.8%)
Abdominal pain 2/17 (11.8%) 2/35 (5.7%) 3/26 (11.5%)
Anal pain 1/17 (5.9%) 0/35 (0%) 0/26 (0%)
Bloating 3/17 (17.6%) 0/35 (0%) 0/26 (0%)
Constipation 12/17 (70.6%) 16/35 (45.7%) 4/26 (15.4%)
Diarrhea 8/17 (47.1%) 10/35 (28.6%) 20/26 (76.9%)
Dry mouth 0/17 (0%) 1/35 (2.9%) 2/26 (7.7%)
Duodenal ulcer 1/17 (5.9%) 0/35 (0%) 0/26 (0%)
Dyspepsia 2/17 (11.8%) 3/35 (8.6%) 1/26 (3.8%)
Dysphagia 1/17 (5.9%) 1/35 (2.9%) 1/26 (3.8%)
Gastroesophageal reflux disease 1/17 (5.9%) 3/35 (8.6%) 2/26 (7.7%)
Gastrointestinal disorders-Other 1/17 (5.9%) 1/35 (2.9%) 0/26 (0%)
Hemorrhoidal hemorrhage 1/17 (5.9%) 0/35 (0%) 0/26 (0%)
Hemorrhoids 2/17 (11.8%) 1/35 (2.9%) 1/26 (3.8%)
Mucositis oral 7/17 (41.2%) 2/35 (5.7%) 13/26 (50%)
Nausea 9/17 (52.9%) 22/35 (62.9%) 19/26 (73.1%)
Rectal pain 1/17 (5.9%) 0/35 (0%) 0/26 (0%)
Small intestinal obstruction 0/17 (0%) 0/35 (0%) 2/26 (7.7%)
Vomiting 4/17 (23.5%) 8/35 (22.9%) 9/26 (34.6%)
General disorders
Chills 2/17 (11.8%) 4/35 (11.4%) 1/26 (3.8%)
Edema face 1/17 (5.9%) 0/35 (0%) 0/26 (0%)
Edema limbs 2/17 (11.8%) 4/35 (11.4%) 5/26 (19.2%)
Facial pain 1/17 (5.9%) 0/35 (0%) 0/26 (0%)
Fatigue 11/17 (64.7%) 33/35 (94.3%) 15/26 (57.7%)
Fever 0/17 (0%) 9/35 (25.7%) 4/26 (15.4%)
Infusion related reaction 3/17 (17.6%) 4/35 (11.4%) 0/26 (0%)
Irritability 1/17 (5.9%) 0/35 (0%) 0/26 (0%)
Non-cardiac chest pain 1/17 (5.9%) 2/35 (5.7%) 0/26 (0%)
Pain 1/17 (5.9%) 6/35 (17.1%) 0/26 (0%)
Immune system disorders
Allergic reaction 0/17 (0%) 3/35 (8.6%) 0/26 (0%)
Cytokine release syndrome 1/17 (5.9%) 0/35 (0%) 0/26 (0%)
Infections and infestations
Catheter related infection 1/17 (5.9%) 1/35 (2.9%) 1/26 (3.8%)
Infections and infestations-Other 1/17 (5.9%) 5/35 (14.3%) 0/26 (0%)
Lung infection 0/17 (0%) 0/35 (0%) 2/26 (7.7%)
Skin infection 0/17 (0%) 2/35 (5.7%) 2/26 (7.7%)
Upper respiratory infection 0/17 (0%) 3/35 (8.6%) 0/26 (0%)
Injury, poisoning and procedural complications
Bruising 1/17 (5.9%) 2/35 (5.7%) 0/26 (0%)
Investigations
Alanine aminotransferase increased 8/17 (47.1%) 8/35 (22.9%) 7/26 (26.9%)
Alkaline phosphatase increased 3/17 (17.6%) 7/35 (20%) 4/26 (15.4%)
Aspartate aminotransferase increased 4/17 (23.5%) 9/35 (25.7%) 6/26 (23.1%)
Blood bilirubin increased 1/17 (5.9%) 7/35 (20%) 5/26 (19.2%)
CD4 lymphocytes decreased 2/17 (11.8%) 2/35 (5.7%) 0/26 (0%)
Carbon monoxide diffusing capacity decreased 1/17 (5.9%) 0/35 (0%) 0/26 (0%)
Cholesterol high 1/17 (5.9%) 0/35 (0%) 0/26 (0%)
Creatinine increased 1/17 (5.9%) 3/35 (8.6%) 2/26 (7.7%)
Electrocardiogram QT corrected interval prolonged 1/17 (5.9%) 1/35 (2.9%) 0/26 (0%)
INR increased 0/17 (0%) 0/35 (0%) 2/26 (7.7%)
Lymphocyte count decreased 11/17 (64.7%) 29/35 (82.9%) 14/26 (53.8%)
Neutrophil count decreased 11/17 (64.7%) 18/35 (51.4%) 18/26 (69.2%)
Platelet count decreased 15/17 (88.2%) 23/35 (65.7%) 19/26 (73.1%)
Weight gain 1/17 (5.9%) 3/35 (8.6%) 2/26 (7.7%)
Weight loss 1/17 (5.9%) 4/35 (11.4%) 3/26 (11.5%)
White blood cell decreased 11/17 (64.7%) 24/35 (68.6%) 20/26 (76.9%)
Metabolism and nutrition disorders
Anorexia 6/17 (35.3%) 12/35 (34.3%) 12/26 (46.2%)
Dehydration 1/17 (5.9%) 1/35 (2.9%) 1/26 (3.8%)
Hyperglycemia 9/17 (52.9%) 14/35 (40%) 8/26 (30.8%)
Hyperkalemia 0/17 (0%) 2/35 (5.7%) 0/26 (0%)
Hypernatremia 1/17 (5.9%) 4/35 (11.4%) 2/26 (7.7%)
Hypertriglyceridemia 1/17 (5.9%) 0/35 (0%) 0/26 (0%)
Hyperuricemia 1/17 (5.9%) 4/35 (11.4%) 2/26 (7.7%)
Hypoalbuminemia 9/17 (52.9%) 7/35 (20%) 11/26 (42.3%)
Hypocalcemia 8/17 (47.1%) 8/35 (22.9%) 17/26 (65.4%)
Hypoglycemia 0/17 (0%) 3/35 (8.6%) 1/26 (3.8%)
Hypokalemia 7/17 (41.2%) 7/35 (20%) 9/26 (34.6%)
Hypomagnesemia 1/17 (5.9%) 2/35 (5.7%) 5/26 (19.2%)
Hyponatremia 5/17 (29.4%) 8/35 (22.9%) 6/26 (23.1%)
Hypophosphatemia 5/17 (29.4%) 3/35 (8.6%) 4/26 (15.4%)
Obesity 1/17 (5.9%) 0/35 (0%) 0/26 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia 3/17 (17.6%) 6/35 (17.1%) 1/26 (3.8%)
Back pain 3/17 (17.6%) 7/35 (20%) 1/26 (3.8%)
Bone pain 1/17 (5.9%) 7/35 (20%) 0/26 (0%)
Generalized muscle weakness 3/17 (17.6%) 2/35 (5.7%) 2/26 (7.7%)
Myalgia 1/17 (5.9%) 5/35 (14.3%) 0/26 (0%)
Neck pain 0/17 (0%) 2/35 (5.7%) 0/26 (0%)
Pain in extremity 0/17 (0%) 7/35 (20%) 2/26 (7.7%)
Nervous system disorders
Cognitive disturbance 1/17 (5.9%) 1/35 (2.9%) 0/26 (0%)
Dizziness 3/17 (17.6%) 5/35 (14.3%) 0/26 (0%)
Dysgeusia 2/17 (11.8%) 3/35 (8.6%) 4/26 (15.4%)
Headache 6/17 (35.3%) 6/35 (17.1%) 3/26 (11.5%)
Nervous system disorders-Other 0/17 (0%) 2/35 (5.7%) 0/26 (0%)
Peripheral motor neuropathy 2/17 (11.8%) 0/35 (0%) 0/26 (0%)
Peripheral sensory neuropathy 4/17 (23.5%) 2/35 (5.7%) 3/26 (11.5%)
Presyncope 1/17 (5.9%) 0/35 (0%) 0/26 (0%)
Seizure 0/17 (0%) 2/35 (5.7%) 0/26 (0%)
Syncope 1/17 (5.9%) 0/35 (0%) 0/26 (0%)
Psychiatric disorders
Agitation 0/17 (0%) 3/35 (8.6%) 0/26 (0%)
Anxiety 3/17 (17.6%) 6/35 (17.1%) 1/26 (3.8%)
Depression 1/17 (5.9%) 2/35 (5.7%) 0/26 (0%)
Insomnia 3/17 (17.6%) 6/35 (17.1%) 3/26 (11.5%)
Renal and urinary disorders
Proteinuria 1/17 (5.9%) 1/35 (2.9%) 1/26 (3.8%)
Urinary frequency 0/17 (0%) 3/35 (8.6%) 1/26 (3.8%)
Urinary incontinence 1/17 (5.9%) 0/35 (0%) 0/26 (0%)
Urinary urgency 1/17 (5.9%) 0/35 (0%) 0/26 (0%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis 0/17 (0%) 2/35 (5.7%) 2/26 (7.7%)
Cough 2/17 (11.8%) 11/35 (31.4%) 4/26 (15.4%)
Dyspnea 2/17 (11.8%) 5/35 (14.3%) 1/26 (3.8%)
Epistaxis 4/17 (23.5%) 1/35 (2.9%) 0/26 (0%)
Hiccups 1/17 (5.9%) 1/35 (2.9%) 1/26 (3.8%)
Nasal congestion 0/17 (0%) 2/35 (5.7%) 1/26 (3.8%)
Pleural effusion 1/17 (5.9%) 1/35 (2.9%) 0/26 (0%)
Productive cough 0/17 (0%) 2/35 (5.7%) 0/26 (0%)
Sinus disorder 1/17 (5.9%) 0/35 (0%) 0/26 (0%)
Sore throat 3/17 (17.6%) 2/35 (5.7%) 1/26 (3.8%)
Skin and subcutaneous tissue disorders
Alopecia 8/17 (47.1%) 3/35 (8.6%) 7/26 (26.9%)
Dry skin 0/17 (0%) 4/35 (11.4%) 0/26 (0%)
Nail ridging 1/17 (5.9%) 2/35 (5.7%) 0/26 (0%)
Pain of skin 1/17 (5.9%) 0/35 (0%) 0/26 (0%)
Pruritus 2/17 (11.8%) 3/35 (8.6%) 2/26 (7.7%)
Rash acneiform 1/17 (5.9%) 1/35 (2.9%) 0/26 (0%)
Rash maculo-papular 3/17 (17.6%) 9/35 (25.7%) 2/26 (7.7%)
Scalp pain 1/17 (5.9%) 0/35 (0%) 0/26 (0%)
Skin and subcutaneous tissue disorders - Other 0/17 (0%) 4/35 (11.4%) 1/26 (3.8%)
Vascular disorders
Flushing 1/17 (5.9%) 0/35 (0%) 1/26 (3.8%)
Hot flashes 0/17 (0%) 3/35 (8.6%) 0/26 (0%)
Hypertension 2/17 (11.8%) 11/35 (31.4%) 5/26 (19.2%)
Hypotension 2/17 (11.8%) 6/35 (17.1%) 6/26 (23.1%)
Thromboembolic event 1/17 (5.9%) 1/35 (2.9%) 1/26 (3.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Lymphoma Committee Statistician
Organization SWOG Statistical Center
Phone 206-667-4623
Email
Responsible Party:
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT01412879
Other Study ID Numbers:
  • CDR0000707601
  • S1106
  • U10CA032102
First Posted:
Aug 9, 2011
Last Update Posted:
Oct 29, 2021
Last Verified:
Oct 1, 2021