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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified January 2014 by AIDS Malignancy Clinical Trials Consortium
Sponsor:
Collaborator:
Information provided by (Responsible Party):
AIDS Malignancy Clinical Trials Consortium
ClinicalTrials.gov Identifier:
NCT01775475
First received: January 23, 2013
Last updated: January 6, 2014
Last verified: January 2014
  Purpose

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


Condition Intervention Phase
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
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: vincristine sulfate
Drug: prednisone
Drug: lomustine
Drug: etoposide
Drug: procarbazine hydrochloride
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized, Phase II Trial of CHOP vs. Oral Chemotherapy With Concomitant Antiretroviral Therapy in Patients With HIV-Associated Lymphoma in Sub-Saharan Africa

Resource links provided by NLM:


Further study details as provided by AIDS Malignancy Clinical Trials Consortium:

Primary Outcome Measures:
  • Overall survival [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
    The log-rank test will be used to compare the two treatment arms with respect to overall survival. The one-sided 0.20 significance level will be used for this comparison. Proportional hazards models will be used to evaluate the association between covariates (e.g., CD4 count and HIV viral load) and overall survival.

  • Overall response rate [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
    The overall response rate will be estimated for each of the treatment arms using the binomial proportion and its 95% confidence interval. The two arms will be compared with respect to overall response rate using Fisher's exact test.

  • Progression-free survival [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
    The log-rank test will be used to compare the two treatment arms with respect to progression-free survival.

  • Frequency and severity of adverse events, assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 24 months ] [ Designated as safety issue: Yes ]
    For each treatment arm, the frequency and severity of adverse events will be summarized. For adverse events that occur in more than 5% of either arm, the two treatment arms will be compared with respect to the proportion of patients who experience that adverse event using Fisher's exact test.

  • Proportion of patients who complete treatment [ Time Frame: Up to 18 weeks ] [ Designated as safety issue: No ]
    The two treatment arms will be compared using Fisher's exact test.

  • Proportion of patients who are adherent to antiretroviral therapy [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
    Fisher's exact test will be used to compare the two treatment arms with respect to the proportion of patients who are adherent to antiretroviral therapy.

  • Proportion of patients who are adherent to chemotherapy [ Time Frame: Up to 18 weeks ] [ Designated as safety issue: No ]
    Fisher's exact test will be used to compare the two treatment arms with respect to the proportion of patients who are adherent to chemotherapy.

  • Effects of therapy on HIV control, measured as the change in CD4 count and HIV load [ Time Frame: From baseline to 18 weeks ] [ Designated as safety issue: No ]
    The Wilcoxon rank sum test will be used to compare the two treatment arms with respect to changes in CD4 count and HIV load.


Estimated Enrollment: 90
Study Start Date: June 2014
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (CHOP)
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
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: prednisone
Given PO
Other Names:
  • DeCortin
  • Deltra
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II (oral chemotherapy)
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
Given PO
Other Names:
  • Belustine
  • CCNU
  • CeeNU
Drug: etoposide
Given PO
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: cyclophosphamide
Given PO
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: procarbazine hydrochloride
Given PO
Other Names:
  • Ibenzmethyzin
  • Matulane
  • MIH
  • Natulan
  • PCB
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To compare the efficacy of standard cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (CHOP) and an oral chemotherapy regimen for acquired immune deficiency syndrome (AIDS)-related (AR)-non-Hodgkin lymphoma (NHL) in sub-Saharan Africa with respect to overall survival (OS).

SECONDARY OBJECTIVES:

I. To compare the objectives response rate (ORR) of persons randomized to CHOP and oral chemotherapy.

II. To compare the progression free survival (PFS) of persons randomized to CHOP and oral chemotherapy.

III. To compare the safety and tolerance of persons randomized to CHOP and oral chemotherapy.

TERTIARY OBJECTIVES:

I. To describe the rates of completion of therapy of persons randomized to CHOP and oral chemotherapy.

II. To describe adherence to chemotherapy of persons randomized to CHOP and oral chemotherapy.

III. To describe adherence to antiretroviral therapy of persons randomized to CHOP and oral chemotherapy.

IV. To describe the effects of therapy on HIV control, as measured by cluster of differentiation (CD)4 counts and HIV viral load.

V. To investigate correlates of survival.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

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

ARM II: Patients receive lomustine PO once daily (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.

After completion of study treatment, patients are followed up at 3, 6, 12, 18, and 24 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • Serum creatinine < 3.0 mg/dL (265.2 umol/L)
  • Total bilirubin =< 1.5 institutional upper limit of normal (ULN), unless elevated secondary to lymphomatous involvement of liver or biliary system, or due to other HIV medications (e.g., indinavir, tenofovir, or atazanavir); if secondary to lymphomatous involvement, an initial upper limit of total bilirubin 5 mg/dL (85.5 uM/L) should be utilized - for direct bilirubin > 1.2 mg/dL (20.5 uM/L)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 institutional ULN (unless elevated secondary to lymphomatous involvement of the liver)
  • Participants must have a lumbar puncture with negative cerebral spinal fluid cytology within 6 weeks prior to enrollment; participants must be without evidence for central nervous system (CNS) lymphoma on neurological exam and have no radiographic evidence (if radiographic studies are done) of CNS lymphoma (inclusive of parenchymal, vitreal, or leptomeningeal involvement)
  • Participants must not have had any prior chemotherapy or radiation therapy and no more than 10 days of corticosteroids in the preceding 30 days prior to enrollment
  • All participants must be prescribed combination antiretroviral therapy with the goal of virological suppression using an acceptable regimen that adheres to national guidelines for treatment of HIV infection; non-suppressed, treatment experienced patients, defined as patients with a viral load > 400 copies/mL who have been on antiretroviral therapy for more than 4 months can be enrolled if an alternative antiretroviral therapy (ART) regimen is available that includes at least two ART drugs that, in the opinion of the site investigator, are expected to have activity based on genotypic testing (if available) and treatment history; patients are not allowed to receive zidovudine (azidothymidine [AZT]) as part of concurrent chemotherapy and ART regimen, since it is myelosuppressive; zidovudine may be discontinued and substituted as clinically indicated prior to or at the time of enrollment.
  • Participants of childbearing potential, defined as a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months), must have a pregnancy test within 7 days prior to enrollment and agree to use an effective form of contraception (e.g., barrier contraception, highly effective hormonal contraception)
  • Participants are allowed to have an active infection(s) for which they are receiving drug treatment provided the clinical status is judged to be stable and survival is estimated to be at least 6 weeks
  • Participants must, in the opinion of the investigatory, be capable of complying with the protocol
  • Participants must be able to take oral medications
  • Participants must have a CD4 count performed within 30 days of enrollment

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01775475

Sponsors and Collaborators
AIDS Malignancy Clinical Trials Consortium
Investigators
Principal Investigator: Robert Strother AIDS Associated Malignancies Clinical Trials Consortium
  More Information

No publications provided

Responsible Party: AIDS Malignancy Clinical Trials Consortium
ClinicalTrials.gov Identifier: NCT01775475     History of Changes
Other Study ID Numbers: AMC-068, NCI-2012-01695, U01CA121947
Study First Received: January 23, 2013
Last Updated: January 6, 2014
Health Authority: United States: Data and Safety Monitoring Board
United States: Federal Government
Kenya: Ethical Review Committee
Kenya: Institutional Review Board
Kenya: Ministry of Health
South Africa: Human Research Ethics Committee
South Africa: Medicines Control Council
South Africa: National Health Research Ethics Council
Uganda: National Council for Science and Technology
Uganda: National Drug Authority
Uganda: Research Ethics Committee
Zimbabwe: Medical Research Council

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Immunoblastic
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma, AIDS-Related
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Lymphoma, B-Cell
Leukemia, Lymphoid
Leukemia
Cyclophosphamide
Lomustine
Liposomal doxorubicin
Etoposide phosphate
Doxorubicin

ClinicalTrials.gov processed this record on September 11, 2014