AzTrials
AzTrials

AIDS-related Diffuse Large Cell LymphomaPhase 2NCT01775475

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

A Phase 2 study testing cyclophosphamide, doxorubicin hydrochloride and vincristine sulfate in people with AIDS-related Diffuse Large Cell Lymphoma and AIDS-related Diffuse Mixed Cell Lymphoma, run by AIDS Malignancy Consortium at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
cyclophosphamide, doxorubicin hydrochloride and vincristine sulfate
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
2 sitesin 2 countries
Study dates
15 Sep 2016to 15 Jul 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 26Show fewer
  • 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

Who cannot join

  • 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

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

Kenya1 site

  • Moi Teaching and Referral Hospital

    Eldoret, 4606-30100

Other trials in Kenya

Zimbabwe1 site

  • University of Zimbabwe College of Health Sciences

    Harare

Other trials in Zimbabwe

About this study

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

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:

  1. 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:

  1. 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:

  1. 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.

  1. 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.

Medical subject headings
Lymphoma, AIDS-Related

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • cyclophosphamideDrug

    Also called CPM, CTX, Cytoxan, Endoxan

    Given IV

  • doxorubicin hydrochlorideDrug

    Also called ADM, ADR, Adria, Adriamycin PFS

    Given IV

  • vincristine sulfateDrug

    Also called leurocristine sulfate, VCR, Vincasar PFS

    Given IV

  • prednisoneDrug

    Also called DeCortin, Deltra

    Given PO

  • lomustineDrug

    Also called Belustine, CCNU, CeeNU

    Given PO

  • etoposideDrug

    Also called EPEG, VP-16, VP-16-213

    Given PO

  • cyclophosphamideDrug

    Also called CPM, CTX, Cytoxan, Endoxan

    Given PO

  • procarbazine hydrochlorideDrug

    Also called Ibenzmethyzin, Matulane, MIH, Natulan

    Given PO

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT01775475
Study groupRoleWhat they receive
Arm I (CHOP)Active comparatorPatients 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.
Receives: Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: vincristine sulfate; Drug: prednisone; Other: laboratory biomarker analysis
Arm II (oral chemotherapy)ExperimentalPatients 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.
Receives: Drug: lomustine; Drug: etoposide; Drug: cyclophosphamide; Drug: procarbazine hydrochloride; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival

    Proportion of participants who survived 2 years

    Measured: 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.

    Measured: Up to 24 months

  3. Progression-free Survival

    Proportion of participants who survived without disease progression at 2 years

    Measured: Up to 24 months

  4. Participants Who Experienced an Adverse Event

    Number of participants who experienced an adverse event

    Measured: Up to 24 months

  5. Number of Patients Who Complete Treatment

    Number of patients who complete chemotherapy treatment.

    Measured: 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

    Measured: Up to 24 months

  7. Proportion of Patients Who Are Adherent to Chemotherapy

    Patients who did not miss any doses of chemotherapy

    Measured: 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)

    Measured: From baseline to 18 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jan 2013 (estimated)
  2. Study start15 Sep 2016
  3. Primary completion1 Apr 2021
  4. Study completion15 Jul 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01775475
Sponsor's protocol ID
AMC-068
Other IDs
NCI-2012-01695, U01CA121947
Status last verified
Sep 2022
First submitted
23 Jan 2013
Last updated
10 Oct 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing cyclophosphamide, doxorubicin hydrochloride and vincristine sulfate in people with AIDS-related Diffuse Large Cell Lymphoma and AIDS-related Diffuse Mixed Cell Lymphoma, run by AIDS Malignancy Consortium at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Kenya, Zimbabwe. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (time frame: Up to 24 months). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01775475.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in