Combination Chemotherapy in Treating Patients With Relapsed or Refractory Intermediate-Grade or High-Grade Non-Hodgkin's Lymphoma

A Phase II Study of Sequential Doxorubicin and Topotecan (Dox/Topo) in Relapsed or Refractory Intermediate- or High-Grade Non-Hodgkin's Lymphoma (NHL)

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining doxorubicin and topotecan in treating patients who have relapsed or refractory intermediate-grade or high-grade non-Hodgkin's lymphoma.

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Drug: doxorubicin hydrochloride; Drug: topotecan hydrochloride

Detailed Description

OBJECTIVES:

• Determine the response rate and time to progression in patients with relapsed or refractory intermediate or high grade non-Hodgkin's lymphoma treated with doxorubicin and topotecan.
• Determine the toxicity of this regimen in these patients.

OUTLINE: Patients receive doxorubicin IV over 5-10 minutes on day 1 and topotecan IV over 30 minutes on days 3-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression.

Patients are followed every 6 months for 2 years and annually for the next 3 years.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00936-5067
    • University of Puerto Rico School of Medicine Medical Sciences Campus
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Northeast Alabama Regional Medical Center
  • California
    • La Jolla, California, United States, 92093-0658
      • Rebecca and John Moores UCSD Cancer Center
    • San Diego, California, United States, 92161
      • Veterans Affairs Medical Center - San Diego
    • San Francisco, California, United States, 94115
      • UCSF Comprehensive Cancer Center
    • San Francisco, California, United States, 94121
      • Veterans Affairs Medical Center - San Francisco
  • Delaware
    • Newark, Delaware, United States, 19713
      • CCOP - Christiana Care Health Services
  • District of Columbia
    • Washington, District of Columbia, United States, 20307-5000
      • Walter Reed Army Medical Center
    • Washington, District of Columbia, United States, 20422
      • Veterans Affairs Medical Center - Washington, DC
    • Washington, District of Columbia, United States, 20007
      • Lombardi Cancer Center
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Broward General Medical Center
    • Hollywood, Florida, United States, 33021
      • Memorial Regional Hospital Comprehensive Cancer Center
    • Miami Beach, Florida, United States, 33140
      • CCOP - Mount Sinai Medical Center
    • Orlando, Florida, United States, 32804
      • Florida Hospital Cancer Institute
    • West Palm Beach, Florida, United States, 33401
      • Helen and Harry Gray Cancer Institute at Good Samaritan Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Veterans Affairs Medical Center - Chicago (Westside Hospital)
    • Chicago, Illinois, United States, 60637-1470
      • University of Chicago Cancer Research Center
    • Chicago, Illinois, United States, 60640
      • Louis A. Weiss Memorial Hospital
    • River Forest, Illinois, United States, 60305
      • West Suburban Center for Cancer Care
    • Rockford, Illinois, United States, 61108
      • Saint Anthony Medical Center
  • Indiana
    • Fort Wayne, Indiana, United States, 46885-5099
      • Fort Wayne Medical Oncology and Hematology, Incorporated
  • Iowa
    • Bettendorf, Iowa, United States, 52722
      • Hematology Oncology Associates of the Quad Cities
    • Iowa City, Iowa, United States, 52242-1009
      • Holden Comprehensive Cancer Center
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Baptist Hospital East - Louisville
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Marlene and Stewart Greenebaum Cancer Center, University of Maryland
    • Baltimore, Maryland, United States, 21201
      • Veterans Affairs Medical Center - Baltimore
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Memorial Medical Center - University Campus
  • Michigan
    • Saint Joseph, Michigan, United States, 49085
      • Lakeland Medical Center - St. Joseph
  • Minnesota
    • Minneapolis, Minnesota, United States, 55417
      • Veterans Affairs Medical Center - Minneapolis
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Cancer Center
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Veterans Affairs Medical Center - Columbia (Truman Memorial)
    • Columbia, Missouri, United States, 65203
      • Ellis Fischel Cancer Center - Columbia
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63110
      • Barnes-jewish Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68198-7680
      • University of Nebraska Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • CCOP - Southern Nevada Cancer Research Foundation
    • Las Vegas, Nevada, United States, 89106
      • Veterans Affairs Medical Center - Las Vegas
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756-0002
      • Norris Cotton Cancer Center
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper University Hospital
  • New York
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute
    • Buffalo, New York, United States, 14215
      • Veterans Affairs Medical Center - Buffalo
    • Elmhurst, New York, United States, 11373
      • Elmhurst Hospital Center
    • Jamaica, New York, United States, 11432
      • Queens Cancer Center of Queens Hospital
    • Manhasset, New York, United States, 11030
      • CCOP - North Shore University Hospital
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center, NY
    • New York, New York, United States, 10021
      • Weill Medical College of Cornell University
    • Syracuse, New York, United States, 13210
      • State University of New York - Upstate Medical University
    • Syracuse, New York, United States, 13210
      • Veterans Affairs Medical Center - Syracuse
    • Syracuse, New York, United States, 13217
      • CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
  • North Carolina
    • Asheville, North Carolina, United States, 28805
      • Veterans Affairs Medical Center - Asheville
    • Chapel Hill, North Carolina, United States, 27599-7295
      • Lineberger Comprehensive Cancer Center, UNC
    • Concord, North Carolina, United States, 28025
      • NorthEast Oncology Associates
    • Durham, North Carolina, United States, 27705
      • Veterans Affairs Medical Center - Durham
    • Durham, North Carolina, United States, 27710
      • Duke Comprehensive Cancer Center
    • Fayetteville, North Carolina, United States, 28302-2000
      • Cape Fear Valley Health System
    • Kinston, North Carolina, United States, 28503-1678
      • Lenoir Memorial Hospital Cancer Center
    • Pinehurst, North Carolina, United States, 28374
      • FirstHealth Moore Regional Hospital
    • Wilmington, North Carolina, United States, 28402-9025
      • New Hanover Regional Medical Center
    • Winston-Salem, North Carolina, United States, 27104-4241
      • CCOP - Southeast Cancer Control Consortium
    • Winston-Salem, North Carolina, United States, 27157-1082
      • Comprehensive Cancer Center at Wake Forest University
  • North Dakota
    • Fargo, North Dakota, United States, 58102
      • Veterans Affairs Medical Center - Fargo
  • Ohio
    • Columbus, Ohio, United States, 43210-1240
      • Arthur G. James Cancer Hospital - Ohio State University
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Lifespan: The Miriam Hospital
  • Texas
    • Dallas, Texas, United States, 75216
      • Veterans Affairs Medical Center - Dallas
  • Vermont
    • Bennington, Vermont, United States, 05201
      • Green Mountain Oncology Group
    • Burlington, Vermont, United States, 05401-3498
      • Vermont Cancer Center
    • White River Junction, Vermont, United States, 05009
      • Veterans Affairs Medical Center - White River Junction
  • Virginia
    • Charlottesville, Virginia, United States, 22901
      • Martha Jefferson Hospital
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates - Norfolk
    • Richmond, Virginia, United States, 23298-0037
      • MBCCOP - Massey Cancer Center
    • Roanoke, Virginia, United States, 24014
      • Oncology and Hematology Associates of Southwest Virginia, Inc.
  • West Virginia
    • Huntington, West Virginia, United States, 25701
      • St. Mary's Medical Center
  • Wisconsin
    • Rhinelander, Wisconsin, United States, 54501
      • Ministry Medical Group - Northern Region

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed recurrent or refractory non-Hodgkin's lymphoma of one of the following subtypes:

  • Follicular center lymphoma, grade 3
  • Diffuse large B-cell lymphoma
  • Diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma
  • Burkitt's lymphoma
  • High grade B-cell lymphoma, Burkitt-like
  • Anaplastic large cell lymphoma, CD30+ cell type
  • Anaplastic large cell lymphoma, T-cell type
  • Anaplastic large cell lymphoma, null-cell type
  • Anaplastic large cell lymphoma, Hodgkin's like
• Bidimensionally measurable disease NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age:

• Any age

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm3
• Platelet count at least 100,000/mm3

Hepatic:

• Bilirubin no greater than 2.0 mg/dL history of Gilbert's Disease
• AST no greater than 2.5 times upper limit of normal

Renal:

• Creatinine normal

Cardiovascular:

• LVEF at least 45% by MUGA or echocardiogram

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Greater than 3 weeks since prior chemotherapy (6 weeks since prior nitrosoureas or mitomycin)
• No greater than 96 mg/m2 mitoxantrone
• No greater than 400 mg/m2 prior doxorubicin or combined total doxorubicin and mitoxantrone
• No prior camptothecins
• No other concurrent chemotherapy

Endocrine therapy:

• No concurrent hormonal therapy except steroids for adrenal failure or hormones given for nondisease conditions (e.g., insulin for diabetes)
• No concurrent dexamethasone or other steroidal antiemetics

Radiotherapy:

• Greater than 3 weeks since prior radiotherapy
• No concurrent radiotherapy except whole brain irradiation for documented CNS disease

Surgery:

• Not specified

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Doxorubicin + topotecan; Patients receive doxorubicin IV over 5-10 minutes on day 1 and topotecan IV over 30 minutes on days 3-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression. Patients are followed every 6 months for 2 years and annually for the next 3 years.	Drug: doxorubicin hydrochloride; Drug: topotecan hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Response rate	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to progression	Up to 5 years

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Nancy L. Bartlett, MD, Washington University Siteman Cancer Center

Publications and helpful links

General Publications

• Smith SM, Johnson JL, Niedzwiecki D, Eder JP, Canellos G, Cheson BD, Bartlett NL; Cancer and Leukemia Group B. Sequential doxorubicin and topotecan in relapsed/refractory aggressive non-Hodgkin's lymphoma: results of CALGB 59906. Leuk Lymphoma. 2006 Aug;47(8):1511-7. doi: 10.1080/10428190600581385.
• Smith SM, Johnson JL, Niedzwiecki D, et al.: Sequential topoisomerase I (topo I) and topoisomerase II (topo II) inhibitors in relapsed/refractory aggressive NHL: results of CALGB 59906, a phase II study of doxorubicin and topotecan. [Abstract] Blood 104 (11): A-2500, 2004.

Study record dates

Study Major Dates

• Study Start: July 1, 2000
• Primary Completion (Actual): August 1, 2006

Study Registration Dates

• First Submitted: August 3, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): July 14, 2016
• Last Update Submitted That Met QC Criteria: July 12, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: recurrent grade 3 follicular lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult Burkitt lymphoma; anaplastic large cell lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Topoisomerase I Inhibitors; Doxorubicin; Liposomal doxorubicin; Topotecan
• Other Study ID Numbers: CALGB-59906; U10CA031946 (U.S. NIH Grant/Contract); CLB-59906; CDR0000068140 (Registry Identifier: NCI Physician Data Query)