Intravenous Chemotherapy or Oral Chemotherapy in Treating Patients With Previously Untreated Stage III-IV HIV-Associated Non-Hodgkin Lymphoma

NCT01775475 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: AMC-068NCI-2012-01695U01CA121947
• Study Type: interventional
• Target: 7
• Locations: 2 countries
• Sites: 2

Brief Summary

This randomized phase II trial studies how well intravenous (IV) chemotherapy or oral chemotherapy works in treating patients with previously untreated stage III-IV human immunodeficiency virus (HIV)-associated non-Hodgkin lymphoma. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone, lomustine, etoposide, and procarbazine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells

Conditions

AIDS-related Diffuse Large Cell Lymphoma; AIDS-related Diffuse Mixed Cell Lymphoma; AIDS-related Diffuse Small Cleaved Cell Lymphoma; AIDS-related Immunoblastic Large Cell Lymphoma; AIDS-related Lymphoblastic Lymphoma; AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Small Noncleaved Cell Lymphoma; Stage III AIDS-related Lymphoma; Stage IV AIDS-related Lymphoma

Outcome Measures

Primary Outcomes (8)

• Overall Survival

  Proportion of participants who survived 2 years

  Up to 24 months

• Overall Response Rate

  Overall response is complete or partial response as defined by response definitions of the 2014 International Conference on Malignant Lymphoma Imaging Working Group (i.e. Lugano classification). Complete response is the disappearance of all lesions with no new lesions detected. Partial response is \>=50% decrease in the sum of the perpendicular diameters of up to 6 target measurable nodes and extranodal sites and no new sites of disease.

  Up to 24 months

• Progression-free Survival

  Proportion of participants who survived without disease progression at 2 years

  Up to 24 months

• Participants Who Experienced an Adverse Event

  Number of participants who experienced an adverse event

  Up to 24 months

• Number of Patients Who Complete Treatment

  Number of patients who complete chemotherapy treatment.

  Up to 18 weeks

• Proportion of Patients Who Are Adherent to Antiretroviral Therapy

  Number of patients who did not miss any of their doses of antiretroviral therapy

  Up to 24 months

• Proportion of Patients Who Are Adherent to Chemotherapy

  Patients who did not miss any doses of chemotherapy

  Up to 18 weeks

• Change in Absolute CD4 Count From Baseline to Post-treatment

  Change in absolute CD4 count from baseline to post-treatment (visit 6)

  From baseline to 18 weeks

Study Arms (2)

Arm I (CHOP)

ACTIVE COMPARATOR

Patients receive CHOP chemotherapy comprising cyclophosphamide IV on day 1, doxorubicin hydrochloride IV on day 1, vincristine sulfate IV on day 1, and prednisone PO on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: vincristine sulfate; Drug: prednisone; Other: laboratory biomarker analysis

Arm II (oral chemotherapy)

EXPERIMENTAL

Patients receive lomustine PO QD on day 1 (courses 1 and 3 only), etoposide PO QD on days 1-3, cyclophosphamide PO QD on days 22-26, and procarbazine hydrochloride PO QD on days 22-26. Treatment repeats every 6 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Drug: lomustine; Drug: etoposide; Drug: cyclophosphamide; Drug: procarbazine hydrochloride; Other: laboratory biomarker analysis

Interventions

cyclophosphamide DRUG

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana

Arm I (CHOP)

doxorubicin hydrochloride DRUG

Given IV

Also known as: ADM, ADR, Adria, Adriamycin PFS, Adriamycin RDF

Arm I (CHOP)

vincristine sulfate DRUG

Given IV

Also known as: leurocristine sulfate, VCR, Vincasar PFS

Arm I (CHOP)

prednisone DRUG

Given PO

Also known as: DeCortin, Deltra

Arm I (CHOP)

lomustine DRUG

Given PO

Also known as: Belustine, CCNU, CeeNU

Arm II (oral chemotherapy)

etoposide DRUG

Given PO

Also known as: EPEG, VP-16, VP-16-213

Arm II (oral chemotherapy)

procarbazine hydrochloride DRUG

Given PO

Also known as: Ibenzmethyzin, Matulane, MIH, Natulan, PCB

Arm II (oral chemotherapy)

laboratory biomarker analysis OTHER

Correlative studies

Arm I (CHOP); Arm II (oral chemotherapy)

Eligibility Criteria

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

You may qualify if:

• Ability to understand and the willingness to provide written informed consent to participate
• Adults, 18 years of age or older; date of birth should be determined based on the best possible information or source documentation available
• HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or confirmed by HIV-1 antigen or plasma HIV-1 ribonucleic acid (RNA) viral load \> 1,000 copies/mL
• NOTE: the term "licensed" refers to a United States (U.S.) Food and Drug Administration (FDA)-approved kit or for sites located in countries other than the United States, a kit that has been certified or licensed by an oversight body within that country and validated internally
• WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment; a reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load
• Biopsy-proven, measurable or assessable systemic NHL that has been confirmed by an AIDS Malignancy Clinical Trial Consortium (AMC)-approved site pathologist; if a hard copy of the pathology report is unavailable at the time of enrollment, a verbal report by the pathologist confirming the diagnosis must be documented in the medical chart
• Pathology slides from tumor tissue obtained by surgical excision or core biopsy must be reviewed by the designated site pathologist, or backup pathologist, prior to study entry; confirmation of the diagnosis must be documented by the AMC-approved pathologist prior to study entry; please reference the AMC-068 Manual of Procedures (MOP) for further instructions on documenting the diagnosis; the site pathologist for NHL must be approved through the AMC's external quality assessment (EQA) process
• Participants must have fifteen blank(unstained) slides or a diagnostic tissue block must be available for central pathology review by the AMC Core Pathology Laboratory
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-3
• Participants must have an estimated life expectancy of \> 6 weeks
• White blood cells (WBC) \>= 3,000 cells/uL (3.0 x 10\^9 L) or
• Absolute granulocytes \>= 1500 cells/uL (1.5 x 10\^9 L)
• Platelets \>= 100,000 cells/uL (75 x 10\^9 L)
• Hemoglobin \> 8 g/dL (5.0 mmol/L)
• Patients may enroll with lower hematologic values, if bone marrow involvement is documented; in this case, patients should be transfused to hemoglobin \> 8 g/dL

You may not qualify if:

• Inability to provide informed consent
• A medical or psychiatric illness that precludes ability to give informed consent or is likely to interfere with the ability to comply with the protocol stipulations
• Participants with circumstances that will not permit completion of the study or required follow-up; for instance, if travel to and from treatment site is an issue
• Pregnant or breastfeeding
• Inability to swallow oral medications

Sponsors & Collaborators

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

Study Sites (2)

Moi Teaching and Referral Hospital

Eldoret, 4606-30100, Kenya

Location

University of Zimbabwe College of Health Sciences

Harare, Zimbabwe

Location

MeSH Terms

Conditions

Lymphoma, AIDS-Related

Interventions

Cyclophosphamide; Doxorubicin; Vincristine; Prednisone; Lomustine; Etoposide; Procarbazine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Benzamides; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives

Results Point of Contact

• Title: Study Statistician
• Organization: AIDS Malignancy Consortium Statistical and Data Analysis Center

amcpm@emmes.com

(212) 659-9558

Study Officials

• Robert Strother

  AIDS Associated Malignancies Clinical Trials Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: January 23, 2013
• First Posted: January 25, 2013
• Study Start: September 15, 2016
• Primary Completion: April 1, 2021
• Study Completion: July 15, 2021
• Last Updated: October 10, 2022
• Results First Posted: October 10, 2022

Record last verified: 2022-09

Locations

ZI (1); KE (1)