Combination Chemotherapy and Rituximab in Treating Patients With Newly Diagnosed AIDS-Related B-Cell Non-Hodgkin's Lymphoma

NCT00389818 | Completed Phase 2 Results

• 3 other identifiers: AMC-047U01CA070019CDR0000507634
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 14

Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. 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. Giving combination chemotherapy together with rituximab may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with rituximab works in treating patients with newly diagnosed AIDS-related B-cell non-Hodgkin's lymphoma.

Conditions

Lymphoma

Keywords

contiguous stage II grade 3 follicular lymphoma; noncontiguous stage II grade 3 follicular lymphoma; stage I grade 3 follicular lymphoma; stage III grade 3 follicular lymphoma; stage IV grade 3 follicular lymphoma; AIDS-related diffuse large cell lymphoma; contiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; stage I adult diffuse large cell lymphoma; stage III adult diffuse large cell lymphoma; stage IV adult diffuse large cell lymphoma; AIDS-related immunoblastic large cell lymphoma; contiguous stage II adult immunoblastic large cell lymphoma; noncontiguous stage II adult immunoblastic large cell lymphoma; stage I adult immunoblastic large cell lymphoma; stage III adult immunoblastic large cell lymphoma; stage IV adult immunoblastic large cell lymphoma; AIDS-related peripheral/systemic lymphoma

Outcome Measures

Primary Outcomes (4)

• Complete Response Rate (Complete Response and Complete Response Unconfirmed) Defined as Disappearance of All Evidence of Disease Based on Radiographic Findings on CT or MRI .

  After cycles 2, 4, 6, 1 month after treatment discontinuation, every 2 months for 1 year after treatment discontinuation, every 6 months during the second and third years after treatment discontinuation

• Duration of Response

  After cycles 2, 4, 6, 1 month after treatment discontinuation, every 2 months for 1 year after treatment discontinuation, every 6 months during the second and third years after treatment discontinuation

• Median Survival Time

  After cycles 2, 4, 6, 1 month after treatment discontinuation, every 2 months for 1 year after treatment discontinuation, every 6 months during the second and third years after treatment discontinuation

• Rate of Bacterial, Fungal, and Opportunistic Infections

  After every cycle of treatment, 1 month after treatment discontinuation, every 2 months for 1 year after treatment discontinuation, every 6 months during the second and third years after treatment discontinuation

Secondary Outcomes (5)

• Relationship Between MDR-1 Expression and Response to Treatment

  Baseline

• Relationship Between Response and Survival and BCL-2 Expression in Tumor Tissue

  Baseline, after cycles 4 and 6, 1 month after treatment discontinuation

• Relationship Between Development of Bacterial, Fungal, and/or Opportunistic Infections and Baseline CD4 Lymphocyte Count, HIV-1 RNA Level, and Quantitative Immunoglobin Level, or Changes in Quantitative Immunoglobin Levels Over Time

  After every cycle of treatment, 1 month after treatment discontinuation, every 2 months for 1 year after treatment discontinuation, every 6 months during the second and third years after treatment discontinuation

• Mortality and Cause of Death

  At any time through the third year after treatment discontinuation

• Event-free Survival at 1 Year

  1 year post-treatment

Study Arms (1)

DR-COP

EXPERIMENTAL

Single arm interventional study: all subjects receive DR-COP regimen.

Biological: filgrastim; Biological: pegfilgrastim; Biological: rituximab; Biological: sargramostim; Drug: cyclophosphamide; Drug: pegylated liposomal doxorubicin hydrochloride; Drug: prednisone; Drug: vincristine sulfate; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis

Interventions

filgrastim BIOLOGICAL

Supportive therapy: GF therapy with G-CSF, GM-CSF, or pegfilgrastim will be used in all patients, beginning on Day 3 of each cycle, until post nadir of blood counts from each chemotherapy cycle.

DR-COP

pegfilgrastim BIOLOGICAL

GF therapy with G-CSF, GM-CSF, or pegfilgrastim will be used in all patients, beginning on Day 3 of each cycle, until post nadir of blood counts from each chemotherapy cycle.

DR-COP

rituximab BIOLOGICAL

375 mg/m2 IV Day 1 of each cycle

DR-COP

sargramostim BIOLOGICAL

GF therapy with G-CSF, GM-CSF, or pegfilgrastim will be used in all patients, beginning on Day 3 of each cycle, until post nadir of blood counts from each chemotherapy cycle.

DR-COP

cyclophosphamide DRUG

750 mg/m2 IV Day 1 of each cycle

DR-COP

pegylated liposomal doxorubicin hydrochloride DRUG

40 mg/m2 IV Day 1 of each cycle

DR-COP

prednisone DRUG

100 mg PO Days 1-5 of each cycle

DR-COP

vincristine sulfate DRUG

1.4 mg/m2 IV Day 1 (2.0 mg maximum) of each cycle

DR-COP

immunohistochemistry staining method OTHER

tissue specimen collected at baseline

DR-COP

laboratory biomarker analysis OTHER

tissue specimen collected at baseline

DR-COP

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed AIDS-related B-cell non-Hodgkin's lymphoma (NHL), including any of the following subtypes: * Grade III follicular large cell lymphoma * Diffuse large B-cell lymphoma * Immunoblastic lymphoma * Plasmablastic lymphoma * Primary effusion lymphoma * Previously untreated disease * Any stage disease * CD20 positive disease * Must have documented HIV infection * Documentation may be by serology (enzyme-linked immunosorbent assay, western blot), culture, or quantitative polymerase chain reaction or branched DNA assays * Prior documentation of HIV seropositivity allowed * Measurable or nonmeasurable disease * Currently receiving effective highly active anti-retroviral therapy * No primary CNS lymphoma, including parenchymal brain or spinal cord lymphoma * No presence of leptomeningeal disease (positive cerebrospinal fluid for lymphoma) or presence of metastatic disease to brain, in terms of any mass lesion PATIENT CHARACTERISTICS: * ECOG performance status (PS) 0-2 OR Karnofsky PS 50-100% * Life expectancy ≥ 2 months * Absolute granulocyte (neutrophil) count ≥ 1,000/mm³ (unless secondary to lymphomatous involvement of bone marrow) * Platelet count ≥ 75,000/mm³ (unless secondary to lymphomatous involvement of bone marrow or due to HIV-related thrombocytopenia) * Bilirubin ≤ 2.0 mg/dL (unless elevated secondary to lymphomatous involvement of liver or biliary system or due to other HIV medications \[e.g., indinavir, tenofavir, or atazanavir\]) * SGOT ≤ 5 times upper limit of normal * Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 60 mL/min (unless secondary to renal involvement by lymphoma) * LVEF normal by MUGA or echocardiogram * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 6 months after completion of study treatment * No other malignancy, except nonmelanoma skin cancer, carcinoma in situ of the cervix, or Kaposi's sarcoma that does not require systemic therapy * No serious, ongoing, nonmalignant disease or infection that would preclude study compliance, in the opinion of the investigator * No history of cutaneous or mucocutaneous reactions, or diseases in the past, due to any cause, severe enough to cause hospitalization or an inability to eat or drink for ≥ 2 days * No acute, intercurrent infection that would preclude study treatment * Patients with Mycobacterium avium are eligible * No cardiovascular problems, including any of the following: * Myocardial infarction within the past 6 months * New York Heart Association class II-IV heart failure * Uncontrolled angina * Severe uncontrolled ventricular arrhythmias * Clinically significant pericardial disease * ECG evidence of acute ischemic or active conduction system abnormalities. * No shortness of breath at rest * Arterial PO\_2 ≥ 70 or pulse oximeter-derived O\_2 saturation ≥ 94% on room air (unless due to lymphomatous involvement of the lungs) * Able to comply with study and provide adequate informed consent PRIOR CONCURRENT THERAPY: * See Disease Characteristics * At least 4 weeks since prior major surgery (except diagnostic surgery) * At least 12 months since prior rituximab unless it was only given for indications other than the treatment of aggressive lymphoma * No prior cytotoxic chemotherapy or radiotherapy for this lymphoma * Concurrent radiotherapy, with or without steroids, for emergency conditions secondary to lymphoma (i.e., CNS tumor or cord compression) allowed * No zidovudine or zidovudine-containing regimen (including Combivir® or Trizivir®) during and for 2 months after completion of chemotherapy * Concurrent erythropoietin or filgrastim (G-CSF) allowed * Growth factor therapy must be discontinued ≥ 24 hours prior to study entry

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• AIDS Malignancy Consortium: lead
• National Cancer Institute (NCI): collaborator
• The Emmes Company, LLC: collaborator

Study Sites (14)

Rebecca and John Moores UCSD Cancer Center

La Jolla, California, 92093-0658, United States

Location

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, 90089-9181, United States

Location

UCLA Clinical AIDS Research and Education (CARE) Center

Los Angeles, California, 90095-1793, United States

Location

University of Miami Sylvester Comprehensive Cancer Center - Miami

Miami, Florida, 33136, United States

Location

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, 60611-3013, United States

Location

Ochsner Cancer Institute at Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Boston University Cancer Research Center

Boston, Massachusetts, 02118, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, 63110, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Albert Einstein Cancer Center at Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

Joan Karnell Cancer Center at Pennsylvania Hospital

Philadelphia, Pennsylvania, 19106, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

Related Publications (1)

• Levine AM, Noy A, Lee JY, Tam W, Ramos JC, Henry DH, Parekh S, Reid EG, Mitsuyasu R, Cooley T, Dezube BJ, Ratner L, Cesarman E, Tulpule A. Pegylated liposomal doxorubicin, rituximab, cyclophosphamide, vincristine, and prednisone in AIDS-related lymphoma: AIDS Malignancy Consortium Study 047. J Clin Oncol. 2013 Jan 1;31(1):58-64. doi: 10.1200/JCO.2012.42.4648. Epub 2012 Nov 19.

  PMID: 23169503 RESULT

MeSH Terms

Conditions

Lymphoma; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Immunoblastic

Interventions

Filgrastim; pegfilgrastim; Rituximab; sargramostim; Cyclophosphamide; Prednisone; Vincristine; Immunohistochemistry

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Immunologic Techniques

Results Point of Contact

• Title: Ronald Mitsuyasu, MD
• Organization: AMC

rmitsuya@mednet.ucla.edu

310-557-1803

Study Officials

• Alexandra M. Levine, MD

  City of Hope Comprehensive Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2006
• First Posted: October 19, 2006
• Study Start: January 1, 2007
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: June 6, 2018
• Results First Posted: June 29, 2012

Record last verified: 2018-05

Locations

US (14)