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CompletedNCT01775475Updated Oct 10, 2022Results posted

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

A Phase 2 interventional study of cyclophosphamide and doxorubicin hydrochloride in AIDS-related Diffuse Large Cell Lymphoma, AIDS-related Diffuse Mixed Cell Lymphoma and AIDS-related Diffuse Small Cleaved Cell Lymphoma, sponsored by AIDS Malignancy Consortium. Completed at 2 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-10-10.

Sponsored by AIDS Malignancy Consortium · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
7
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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

Read the 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.

02

Conditions studied

  • 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
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
7 participants (actual)

Study arms

  • 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 · Drug: doxorubicin hydrochloride · Drug: vincristine sulfate · Drug: prednisone · Other: laboratory biomarker analysis

  • 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 · Drug: etoposide · Drug: cyclophosphamide · Drug: procarbazine hydrochloride · Other: laboratory biomarker analysis

Interventions

  • Drugcyclophosphamide

    Given IV

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

  • Drugdoxorubicin hydrochloride

    Given IV

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

  • Drugvincristine sulfate

    Given IV

    Also known as: leurocristine sulfate, VCR, Vincasar PFS

  • Drugprednisone

    Given PO

    Also known as: DeCortin, Deltra

  • Druglomustine

    Given PO

    Also known as: Belustine, CCNU, CeeNU

  • Drugetoposide

    Given PO

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

  • Drugcyclophosphamide

    Given PO

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

  • Drugprocarbazine hydrochloride

    Given PO

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

  • Otherlaboratory biomarker analysis

    Correlative studies

05

What researchers measure

Primary outcomes

  1. Overall Survival

    Proportion of participants who survived 2 years

    Time frame: Up to 24 months

  2. 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.

    Time frame: Up to 24 months

  3. Progression-free Survival

    Proportion of participants who survived without disease progression at 2 years

    Time frame: Up to 24 months

  4. Participants Who Experienced an Adverse Event

    Number of participants who experienced an adverse event

    Time frame: Up to 24 months

  5. Number of Patients Who Complete Treatment

    Number of patients who complete chemotherapy treatment.

    Time frame: Up to 18 weeks

  6. Proportion of Patients Who Are Adherent to Antiretroviral Therapy

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

    Time frame: Up to 24 months

  7. Proportion of Patients Who Are Adherent to Chemotherapy

    Patients who did not miss any doses of chemotherapy

    Time frame: Up to 18 weeks

  8. Change in Absolute CD4 Count From Baseline to Post-treatment

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

    Time frame: From baseline to 18 weeks

06

Results

Posted Oct 10, 2022

Participant flow

Participant flow — Overall Study
MilestoneArm I (CHOP)Arm II (Oral Chemotherapy)
Started43
Completed10
Not completed33
Withdrew: Death33

Outcome measures

PrimaryOverall Survival

Proportion of participants who survived 2 years

Time frame:
Up to 24 months
Reported as:
Number · Proportion of participants
Overall Survival
Proportion of participantsArm I (CHOP)Arm II (Oral Chemotherapy)
Overall Survival0 (0 to 0)0 (0 to 0)
PrimaryOverall 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.

Time frame:
Up to 24 months
Reported as:
Count of participants · Participants
Overall Response Rate
ParticipantsArm I (CHOP)Arm II (Oral Chemotherapy)
Overall Response Rate31
PrimaryProgression-free Survival

Proportion of participants who survived without disease progression at 2 years

Time frame:
Up to 24 months
Reported as:
Number · proportion
Progression-free Survival
proportionArm I (CHOP)Arm II (Oral Chemotherapy)
Progression-free Survival0 (0 to 0)0 (0 to 0)
PrimaryParticipants Who Experienced an Adverse Event

Number of participants who experienced an adverse event

Time frame:
Up to 24 months
Reported as:
Count of participants · Participants
Participants Who Experienced an Adverse Event
ParticipantsArm I (CHOP)Arm II (Oral Chemotherapy)
Participants Who Experienced an Adverse Event43
PrimaryNumber of Patients Who Complete Treatment

Number of patients who complete chemotherapy treatment.

Time frame:
Up to 18 weeks
Reported as:
Count of participants · Participants
Number of Patients Who Complete Treatment
ParticipantsArm I (CHOP)Arm II (Oral Chemotherapy)
Number of Patients Who Complete Treatment31
PrimaryProportion of Patients Who Are Adherent to Antiretroviral Therapy

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

Time frame:
Up to 24 months
Reported as:
Count of participants · Participants
Proportion of Patients Who Are Adherent to Antiretroviral Therapy
ParticipantsArm I (CHOP)Arm II (Oral Chemotherapy)
Proportion of Patients Who Are Adherent to Antiretroviral Therapy33
PrimaryProportion of Patients Who Are Adherent to Chemotherapy

Patients who did not miss any doses of chemotherapy

Time frame:
Up to 18 weeks
Reported as:
Count of participants · Participants
Proportion of Patients Who Are Adherent to Chemotherapy
ParticipantsArm I (CHOP)Arm II (Oral Chemotherapy)
Proportion of Patients Who Are Adherent to Chemotherapy43
PrimaryChange in Absolute CD4 Count From Baseline to Post-treatment

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

Time frame:
From baseline to 18 weeks
Reported as:
Mean · cells per mm^3
Change in Absolute CD4 Count From Baseline to Post-treatment
cells per mm^3Arm I (CHOP)Arm II (Oral Chemotherapy)
Change in Absolute CD4 Count From Baseline to Post-treatment-41.3 ± 136.5203.3 ± 153.1

Adverse events

Collected over 2 years. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Arm I (CHOP)3/4 (75%)4/4 (100%)4/4 (100%)
Arm II (Oral Chemotherapy)3/3 (100%)3/3 (100%)3/3 (100%)
Most frequent serious events
Most frequent serious events
EventArm I (CHOP)Arm II (Oral Chemotherapy)
Neoplasms, otherNeoplasms benign, malignant and unspecified (incl cysts and polyps)2/42/3
HeadacheNervous system disorders2/40/3
FeverGeneral disorders0/41/3
Death cause unknownGeneral disorders0/41/3
FatigueGeneral disorders1/40/3
Encephalitis infectionInfections and infestations1/40/3
Febrile neutropeniaBlood and lymphatic system disorders1/40/3
Most frequent other events
Showing 10 of 28
Most frequent other events
EventArm I (CHOP)Arm II (Oral Chemotherapy)
Alkaline phosphataseInvestigations1/42/3
HyponatremiaMetabolism and nutrition disorders1/42/3
Neutrophil count decreasedInvestigations2/41/3
AnemiaBlood and lymphatic system disorders1/41/3
Blood and lymphatic system disorders, otherBlood and lymphatic system disorders1/41/3
TinnitusEye disorders0/41/3
ConstipationGastrointestinal disorders0/41/3
VomitingGastrointestinal disorders1/41/3
Lymphocyte count decreasedInvestigations0/41/3
White blood cell decreasedInvestigations1/41/3

Baseline characteristics

Age, Continuous
Age, Continuous(years)Arm I (CHOP)Arm II (Oral Chemotherapy)Total
Median52.5 (43.0 to 55.0)46.0 (39.0 to 47.0)47.0 (39.0 to 55.0)
Sex: Female, Male
Sex: Female, Male(Participants)Arm I (CHOP)Arm II (Oral Chemotherapy)Total
Female426
Male011
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Arm I (CHOP)Arm II (Oral Chemotherapy)Total
Hispanic or Latino000
Not Hispanic or Latino437
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)Arm I (CHOP)Arm II (Oral Chemotherapy)Total
Zimbabwe101
Kenya123
Malawi213
07

Study locations

2 sites
  • Moi Teaching and Referral Hospital
    Eldoret, 4606-30100, Kenya
  • University of Zimbabwe College of Health Sciences
    Harare, Zimbabwe
08

References and documents

Study documents

  • Protocol and statistical analysis plan · Dec 3, 2019
  • Informed consent form · Dec 3, 2019

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT01775475
Lead sponsor
AIDS Malignancy Consortium
Collaborators
National Cancer Institute (NCI), The Emmes Company, LLC, University of Arkansas
Responsible party
Sponsor
First posted
Jan 25, 2013
Start date
Sep 15, 2016
Primary completion
Apr 1, 2021
Completion
Jul 15, 2021
Results posted
Oct 10, 2022
Last update
Oct 10, 2022

Study contacts

Robert Strother
principal investigator · AIDS Associated Malignancies Clinical Trials Consortium

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
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