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
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
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.
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
Exclusion Criteria:
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
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
Given IV
Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana
Given IV
Also known as: ADM, ADR, Adria, Adriamycin PFS, Adriamycin RDF
Given IV
Also known as: leurocristine sulfate, VCR, Vincasar PFS
Given PO
Also known as: DeCortin, Deltra
Given PO
Also known as: Belustine, CCNU, CeeNU
Given PO
Also known as: EPEG, VP-16, VP-16-213
Given PO
Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana
Given PO
Also known as: Ibenzmethyzin, Matulane, MIH, Natulan, PCB
Correlative studies
Overall Survival
Proportion of participants who survived 2 years
Time frame: 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.
Time frame: Up to 24 months
Progression-free Survival
Proportion of participants who survived without disease progression at 2 years
Time frame: Up to 24 months
Participants Who Experienced an Adverse Event
Number of participants who experienced an adverse event
Time frame: Up to 24 months
Number of Patients Who Complete Treatment
Number of patients who complete chemotherapy treatment.
Time frame: 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
Time frame: Up to 24 months
Proportion of Patients Who Are Adherent to Chemotherapy
Patients who did not miss any doses of chemotherapy
Time frame: 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)
Time frame: From baseline to 18 weeks
| Milestone | Arm I (CHOP) | Arm II (Oral Chemotherapy) |
|---|---|---|
| Started | 4 | 3 |
| Completed | 1 | 0 |
| Not completed | 3 | 3 |
| Withdrew: Death | 3 | 3 |
Proportion of participants who survived 2 years
| Proportion of participants | Arm I (CHOP) | Arm II (Oral Chemotherapy) |
|---|---|---|
| Overall Survival | 0 (0 to 0) | 0 (0 to 0) |
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.
| Participants | Arm I (CHOP) | Arm II (Oral Chemotherapy) |
|---|---|---|
| Overall Response Rate | 3 | 1 |
Proportion of participants who survived without disease progression at 2 years
| proportion | Arm I (CHOP) | Arm II (Oral Chemotherapy) |
|---|---|---|
| Progression-free Survival | 0 (0 to 0) | 0 (0 to 0) |
Number of participants who experienced an adverse event
| Participants | Arm I (CHOP) | Arm II (Oral Chemotherapy) |
|---|---|---|
| Participants Who Experienced an Adverse Event | 4 | 3 |
Number of patients who complete chemotherapy treatment.
| Participants | Arm I (CHOP) | Arm II (Oral Chemotherapy) |
|---|---|---|
| Number of Patients Who Complete Treatment | 3 | 1 |
Number of patients who did not miss any of their doses of antiretroviral therapy
| Participants | Arm I (CHOP) | Arm II (Oral Chemotherapy) |
|---|---|---|
| Proportion of Patients Who Are Adherent to Antiretroviral Therapy | 3 | 3 |
Patients who did not miss any doses of chemotherapy
| Participants | Arm I (CHOP) | Arm II (Oral Chemotherapy) |
|---|---|---|
| Proportion of Patients Who Are Adherent to Chemotherapy | 4 | 3 |
Change in absolute CD4 count from baseline to post-treatment (visit 6)
| cells per mm^3 | Arm I (CHOP) | Arm II (Oral Chemotherapy) |
|---|---|---|
| Change in Absolute CD4 Count From Baseline to Post-treatment | -41.3 ± 136.5 | 203.3 ± 153.1 |
Collected over 2 years. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| 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%) |
| Event | Arm I (CHOP) | Arm II (Oral Chemotherapy) |
|---|---|---|
| Neoplasms, otherNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 2/4 | 2/3 |
| HeadacheNervous system disorders | 2/4 | 0/3 |
| FeverGeneral disorders | 0/4 | 1/3 |
| Death cause unknownGeneral disorders | 0/4 | 1/3 |
| FatigueGeneral disorders | 1/4 | 0/3 |
| Encephalitis infectionInfections and infestations | 1/4 | 0/3 |
| Febrile neutropeniaBlood and lymphatic system disorders | 1/4 | 0/3 |
| Event | Arm I (CHOP) | Arm II (Oral Chemotherapy) |
|---|---|---|
| Alkaline phosphataseInvestigations | 1/4 | 2/3 |
| HyponatremiaMetabolism and nutrition disorders | 1/4 | 2/3 |
| Neutrophil count decreasedInvestigations | 2/4 | 1/3 |
| AnemiaBlood and lymphatic system disorders | 1/4 | 1/3 |
| Blood and lymphatic system disorders, otherBlood and lymphatic system disorders | 1/4 | 1/3 |
| TinnitusEye disorders | 0/4 | 1/3 |
| ConstipationGastrointestinal disorders | 0/4 | 1/3 |
| VomitingGastrointestinal disorders | 1/4 | 1/3 |
| Lymphocyte count decreasedInvestigations | 0/4 | 1/3 |
| White blood cell decreasedInvestigations | 1/4 | 1/3 |
| Age, Continuous(years) | Arm I (CHOP) | Arm II (Oral Chemotherapy) | Total |
|---|---|---|---|
| Median | 52.5 (43.0 to 55.0) | 46.0 (39.0 to 47.0) | 47.0 (39.0 to 55.0) |
| Sex: Female, Male(Participants) | Arm I (CHOP) | Arm II (Oral Chemotherapy) | Total |
|---|---|---|---|
| Female | 4 | 2 | 6 |
| Male | 0 | 1 | 1 |
| Ethnicity (NIH/OMB)(Participants) | Arm I (CHOP) | Arm II (Oral Chemotherapy) | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 |
| Not Hispanic or Latino | 4 | 3 | 7 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | Arm I (CHOP) | Arm II (Oral Chemotherapy) | Total |
|---|---|---|---|
| Zimbabwe | 1 | 0 | 1 |
| Kenya | 1 | 2 | 3 |
| Malawi | 2 | 1 | 3 |
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