Chemotherapy Based on PET Scan in Treating Patients With Stage I or Stage II Hodgkin Lymphoma

Lymphoma Clinical Trial

Official title:

Phase II Trial of Response-Adapted Therapy Based on Positron Emission Tomography (PET) for Bulky Stage I and II Classical Hodgkin Lymphoma (HL)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01390584
• Other study ID #: E2410
• Secondary ID: U01CA079778U01CA
• Status: Terminated
• Phase: Phase 2
• Start date: May 24, 2013
• Est. completion date: May 18, 2018

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride, bleomycin sulfate, vinblastine, dacarbazine, cyclophosphamide, etoposide, procarbazine hydrochloride, vincristine sulfate, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x rays to kill cancer cells. Giving combination chemotherapy together with radiation therapy may kill more cancer cells. Comparing results of imaging procedures, such as PET scans and CT scans, done before, during, and after chemotherapy may help doctors predict a patient's response to treatment and help plan the best treatment.

PURPOSE: This phase II clinical trial studies how well chemotherapy based on PET/CT scan works in treating patients with stage I or stage II Hodgkin lymphoma.

Description:

OBJECTIVES:

Primary

• To evaluate the progression-free survival (PFS) at 36 months following registration for patients who are positron emission tomography (PET) negative after 2 courses of ABVD, and receive 4 additional courses of doxorubicin hydrochloride, bleomycin sulfate, vinblastine, and dacarbazine (ABVD) followed by involved-nodal radiotherapy [INRT] of 30-30.6 Gy.

Secondary

• To evaluate the PET-negative rate after 2 courses of ABVD chemotherapy in patients with stage I/II Hodgkin lymphoma with bulky mediastinal disease.

• To evaluate the PFS at 36 months for patients who are PET positive after 2 courses of chemotherapy and receive 4 courses of escalated bleomycin sulfate, etoposide, doxorubicin hydrochloride, cyclophosphamide, vincristine sulfate, procarbazine hydrochloride, and prednisone (BEACOPP) followed by INRT of 30-30.6 Gy.

• To evaluate the complete response (CR) rate and overall survival (OS) for PET-positive and PET-negative patients after 2 courses of ABVD.

• To identify sites of relapse following combined-modality therapy (CMT) for patients with large mediastinal adenopathy and correlate with RT fields.

• To assess toxicity on both arms of study.

• To assess reproductive function at baseline and at 3 years after ABVD or escalated BEACOPP with specific serum markers.

• To bank serum and plasma at baseline and selected time points to assess the prognostic value of various markers such as, but not limited to, SCD30, IL10, CCL17, CCL22, and MDC.

• To create tissue microarrays (TMAs) from patient tumor blocks for future biomarker assessment including, but not limited to, bcl-2, FOXP3, and macrophage content.

• To measure serum TARC levels pre-treatment and post two courses of ABVD and correlate with PET-CT findings (performed at same time points) and 3 year PFS.

Tertiary

• To assess the predictive value of fludeoxyglucose F 18 (18FDG) uptake, as measured by semi-quantitative measurements including standard uptake variables (SUVs), with respect to response at the end of chemotherapy and PFS.

• To compare the predictive value for response and PFS of FDG uptake alone to that of FDG uptake in combination with CT size change information.

• To compare the predictive value for response and PFS of FDG uptake alone to that of FDG uptake in combination with available serum and tissue molecular biomarkers.

• To compare the results of the secondary imaging objectives with the corresponding CALGB 50801 results (contingent on reaching agreement with CALGB on the combined analysis of the two studies).

OUTLINE: This is a multicenter study.

Induction ABVD chemotherapy: Patients receive doxorubicin hydrochloride IV, bleomycin sulfate IV, vinblastine IV over 3-5 minutes, and dacarbazine IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.

Patients are then assigned to an intervention arm according to fludeoxyglucose F 18 (18 FDG) positron emission tomography (PET)/computed tomography (CT) results (negative vs positive).

• ABVD (18FDG-PET/CT negative): Patients receive doxorubicin hydrochloride, bleomycin sulfate, vinblastine, and dacarbazine as in induction chemotherapy. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Within 3-6 weeks after completion of chemotherapy, patients undergo involved-node radiotherapy (INRT) 5 days a week for approximately 3½ weeks.

• Escalated or standard BEACOPP* (18FDG-PET/CT positive): Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV over 60 minutes on day 1, etoposide IV over 60 minutes on days 1-3, procarbazine hydrochloride orally (PO) on days 1-7, prednisone PO on days 1-14, and bleomycin sulfate IV and vincristine sulfate IV on day 8. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Within 3-6 weeks after completion of chemotherapy, patients who achieve complete response with a negative 18FDG-PET/CT scan undergo INRT 5 days a week for approximately 3½ weeks.

NOTE: *HIV-positive patients whose 18FDG-PET/CT scans are positive after two courses of induction ABVD receive 4 courses of standard BEACOPP followed by INRT.

Patients undergo 18FDG-PET scans at baseline, and within 8-10 days after 2 courses of ABVD induction chemotherapy. Patients also undergo 18FDG-PET/CT** scan within 3-8 weeks after completion of 4 courses of BEACOPP and 6 courses of ABVD, and 3 months after completion of INRT.

NOTE: **If PET/CT remains positive, then a biopsy may be performed if medically appropriate or clinically feasible at the discretion of the treating physician. If biopsy is positive, patients will be followed for survival and secondary malignancies or new primaries.

Patients may undergo blood sample collection for correlative studies.

After completion of study therapy, patients are followed up every 3 months for 1 year, every 6 months for 2 years, and then annually for up to 10 years.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: May 18, 2018
• Est. primary completion date: April 9, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically proven classical Hodgkin lymphoma subclassified according to the World Health Organization (WHO) Classification of Tumors, 4th edition (2008)

• Patients must have clinical stage IA, IB, IIA, or IIB disease

• Patients with "E" extensions will be eligible if all other criteria have been met

• Patients must have a mediastinal mass > 0.33-cm maximum intrathoracic diameter on standing postero-anterior chest x-ray or measuring > 10 cm in its largest diameter on axial CT images

• Bone marrow biopsy is required

• ECOG performance status 0-2

• ANC = 1,000/µL

• Platelet count = 100,000/µL

• Hemoglobin = 10 g/dL

• Serum creatinine = 2 mg/dL

• Direct bilirubin = 2 mg/dL

• AST/ALT = 2 times upper limit of normal

• Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception

• LVEF by ECHO or MUGA normal unless thought to be disease related

• DLCO = 60% with no symptomatic pulmonary disease unless thought to be disease related

• Patients with a history of intravenous drug abuse, or any behavior associated with an increased risk of HIV infection, should be tested for exposure to the HIV virus, and an HIV test is required for entry on this protocol

• HIV-positive patients are eligible if they have CD4 counts = 400/mm³ and are on concurrent antiretrovirals

• Patient HIV status must be known prior to registration

• HIV-positive patients must not have multi-drug resistant HIV infections; CD4 counts < 400/mm³; or other concurrent AIDS-defining conditions

• Concurrent antiretroviral therapy for HIV-positive patients (CD4 counts = 400/mm³) allowed

Exclusion Criteria:

• Nodular lymphocyte-predominant Hodgkin lymphoma

• Pregnant or nursing

• "Currently active" second malignancy other than non-melanoma skin cancers

• Patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse

• Prior treatment (chemotherapy or radiation therapy) for Hodgkin lymphoma

Related Conditions & MeSH terms

• Hodgkin Disease
• Lymphoma

Intervention

Drug:
• Doxorubicin
IV
• Bleomycin
IV
• Vinblastine
IV

Diagnostic Test:
• PET
fludeoxyglucose F 18 Imaging exam

Radiation:
• INRT
selective external radiation therapy

Drug:
• Dacarbazine
IV
• Etoposide
IV
• Cyclophosphamide
May be given orally, IV push, or by IV infusion
• Vincristine
IV
• Procarbazine
PO
• Prednisone
PO

Locations

Country	Name	City	State
United States	McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center	Reading	Pennsylvania
United States	Stanford Cancer Center	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
ECOG-ACRIN Cancer Research Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival Rate	Progression-free survival is defined as the time from study entry to lymphoma progression or death from any cause. Proportion of patients who are progression-free and alive at 36 months will be reported. Progression is defined as appearance of any new lesions more than 1.5 cm in any axis, at least a 50% increase from nadir in sum of the product of the diameters (SPD) of any previously involved nodes or extranodal masses or the size of other lesions, or at least 50% increase in the longest diameter of any single previously identified node or extranodal mass more than 1 cm in its short axis.	Assessed at 36 months
Secondary	Proportion of Patients Who Are PET Negative After Induction Treatment		Assessed at end of Cycle 2
Secondary	Progression-free Survival at 36 Months Among Patients Who Are PET Positive After Induction Treatment	Progression-free survival is defined as the time from study entry to lymphoma progression or death from any cause. Proportion of patients who are progression-free and alive at 36 months will be reported. Progression is defined as appearance of any new lesions more than 1.5 cm in any axis, at least a 50% increase from nadir in sum of the product of the diameters (SPD) of any previously involved nodes or extranodal masses or the size of other lesions, or at least 50% increase in the longest diameter of any single previously identified node or extranodal mass more than 1 cm in its short axis.	Assessed at 36 months
Secondary	Complete Response (CR) Rate After Induction Treatment	Complete response (CR) is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy.	Assessed at end of Cycle 2
Secondary	Overall Survival	Overall survival is defined as the time from study entry to death or date last known alive.	Assessed at 36 months
Secondary	Sites of Relapse Following Combined Modality Treatment		Assessed at 3, 12, 18, 24 and 36 months after INRT
Secondary	Serum and Plasma Banking	To bank serum and plasma at baseline and follow-up time point to assess the prognostic value of various markers, such as but not limited to, SCD30, IL10, CCL17, CCL22, and MDC.	Baseline and post cycle 2
Secondary	Biomarker Assessment Using Tissue Microarrays (TMAs)	To create TMAs from patient tumor blocks for future biomarker assessment including but not limited to bcl-2, FOXP3, and macrophage content.	Baseline and relapse/progression
Secondary	The Association Between Thymus and Activation-related Chemokine (TARC) Levels and PET-CT Findings as Well as 3-year PFS	To measure serum TARC levels pre-treatment and after two cycles of ABVD and evaluate the associations between TARC levels and PET-CT findings as well as 3-year PFS.	Baseline and cycle 2 for TARC assessments; 3 years for PFS