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Chemotherapy Based on Positron Emission Tomography Scan in Treating Patients With Stage I or Stage II Hodgkin Lymphoma

Phase 2
Completed
Conditions
Lymphoma
Interventions
Biological: Bleomycin Sulfate
Drug: Radiation Therapy
Radiation: Fludeoxyglucose F-18
Procedure: computed tomography
Procedure: Positron Emission Tomography
Registration Number
NCT01132807
Lead Sponsor
Alliance for Clinical Trials in Oncology
Brief Summary

This phase II trial studies how well chemotherapy based on positron emission tomography (PET) scan works in treating patients with stage I or stage II Hodgkin lymphoma. Drugs used in chemotherapy 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. Radiation therapy uses high energy x-rays to kill cancer cells. Giving combination chemotherapy together with radiation therapy may kill more cancer cells and allow doctors to save the part of the body where the cancer started. Comparing results of diagnostic procedures, such as PET scan, done before, during, and after chemotherapy may help doctors predict a patient's response to treatment and help plan the best treatment.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the progression-free survival (PFS) from enrollment for patients with non-bulky stage I and II Hodgkin lymphoma.

II. To compare the PFS of patients who are PET positive versus PET negative following 2 cycles of doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine (ABVD).

SECONDARY OBJECTIVES:

I. To evaluate the complete response (CR) rate of patients diagnosed with non-bulky stage I and II Hodgkin lymphoma following PET response-adapted chemotherapy with or without radiation therapy.

II. To determine the predictive value of fludeoxyglucose (FDG) uptake using various semi-quantitative approaches, at baseline, after 2 cycles of AVBD and at completion of therapy.

III. To determine the predictive value of volumetric changes on computed tomography (CT) vs 2-dimensional (2-D) analyses after 2 cycles and 4 cycles and compare with PET parameters with and without combination analyses (PET + dedicated CT data).

IV. To compare the predictive value of metabolic parameters/changes that are measured both visually and semi-quantitatively, International Harmonization Project (IHP) criteria, 2-D and volumetric CT changes, molecular parameters, and conventional parameters, including International Prognostic Score (IPS).

V. To assess whether elevated baseline circulating markers of inflammation (including soluble cluster of differentiation CD30 \[sCD\]30, soluble CD 163 \[CD163\], interleukin-10 (IL10), chemokine (C-C motif) ligand 17 (CCL17), and chemokine (C-C motif) ligand 22 \[CCL22\]) correlate with clinical response and PFS and PET scan results.

VI. To assess whether persistent or recurrent elevated serial circulating markers of inflammation (including soluble CD30 \[sCD30\], soluble CD163 \[sCD163\], IL10, CCL17, or CCL22) correlate with relapse/progression or PET scan results.

VII. To confirm independently useful tissue biomarkers for risk stratification in patients with non-bulky stage I and II Hodgkin lymphoma treated with this regimen.

VIII. To compare mediastinal bulk on standing posterior-anterior (PA) and lateral chest x-ray (\> 0.33 maximum chest diameter) with chest CT (mass \> 10 cm).

OUTLINE:

ABVD CHEMOTHERAPY: Patients receive doxorubicin hydrochloride intravenously (IV) over 3-5 minutes, bleomycin sulfate IV over 3-5 minutes, 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. Patients then undergo PET scan. Patients achieving complete response (CR), partial response (PR), or stable disease (SD) with a negative PET scan receive 2 additional courses of ABVD chemotherapy in the absence of disease progression or unacceptable toxicity. Patients achieving CR, PR, or SD with a positive PET scan proceed to escalated BEACOPP chemotherapy.

ESCALATED BEACOPP\* CHEMOTHERAPY: Patients receive doxorubicin hydrochloride IV over 3-5 minutes and cyclophosphamide IV over 60 minutes on day 1, etoposide IV over 45-60 minutes on days 1-3, procarbazine orally (PO) on days 1-7, prednisone PO on days 1-14, and bleomycin sulfate IV and vincristine IV on day 8. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Within 4-6 weeks after completion of BEACOPP chemotherapy, patients undergo involved-field radiotherapy (IFRT) 5 days a week for 3½ weeks.

NOTE: \* HIV-positive patients receive standard BEACOPP instead of escalated BEACOPP.

Patients undergo fludeoxyglucose F\^18 PET/CT scan at baseline, and within 8-10 days after completion of chemotherapy. Patients also undergo additional PET/CT scans within 3-4 weeks after completion of ABVD or within 12 weeks after completion of BEACOPP and IFRT. Patients with a negative PET scan proceed to follow up. Patients with a positive PET scan undergo biopsy\*\*. Patients with a negative biopsy proceed to follow up, and patients with a positive biopsy are treated at the discretion of the investigator.

NOTE: \*\* Patients for whom biopsy is neither clinically appropriate nor medically feasible proceed to follow-up. Patients for whom biopsy is neither clinically indicated nor medically appropriate undergo a repeat PET/CT scan after 3 months. If PET/CT scan remains positive, patients undergo biopsy as above.

After completion of study therapy, patients are followed up every 3 months for 1 year, every 6 months for 2-3 years, and then annually for a maximum of 5 years.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
164
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Treatment (chemotherapy and F-18 PET/CT)Radiation TherapySee Detailed Description
Treatment (chemotherapy and F-18 PET/CT)Positron Emission TomographySee Detailed Description
Treatment (chemotherapy and F-18 PET/CT)Bleomycin SulfateSee Detailed Description
Treatment (chemotherapy and F-18 PET/CT)Procarbazine HydrochlorideSee Detailed Description
Treatment (chemotherapy and F-18 PET/CT)Vinblastine SulfateSee Detailed Description
Treatment (chemotherapy and F-18 PET/CT)Etoposide phosphateSee Detailed Description
Treatment (chemotherapy and F-18 PET/CT)computed tomographySee Detailed Description
Treatment (chemotherapy and F-18 PET/CT)Fludeoxyglucose F-18See Detailed Description
Treatment (chemotherapy and F-18 PET/CT)DacarbazineSee Detailed Description
Treatment (chemotherapy and F-18 PET/CT)Doxorubicin HydrochlorideSee Detailed Description
Treatment (chemotherapy and F-18 PET/CT)prednisoneSee Detailed Description
Treatment (chemotherapy and F-18 PET/CT)CyclophosphamideSee Detailed Description
Primary Outcome Measures
NameTimeMethod
Progression-Free Survival (PFS) at 36-Months for Patients Who Received 4 Cycles of ABVD36 Months

The primary objective of this trial is to estimate the 3 year PFS in patients who received 4 cycles of ABVD. PFS for each patient is measured as the time from registration on trial to the first incident of death or progression. The PFS at 36 months is calculated as the number of patients who have a progression-free survival time greater than 36 months divided by the total number of patients that started treatment. For this endpoint, all patients that received 4 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) are included.

36 Month Progression Free Survival Rate of Patients Receiving 4 Cycles of ABVD Versus Patients Receiving 2 Cycles of ABVD and 2 Cycles of BEACOPP and Radiation.at 36 months

All patients received an initial 2-28 day cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15. After the first 2 cycles of ABVD, PET/CT was performed and submitted for central review (cycle 2, days 23-25) and determined whether patients would receive 2 cycles of escalated BEACOPP and involved-field RT (IFRT) or an additional 2 cycles of ABVD. PFS for each patient is measured as the time from registration on trial to the first incident of death or progression. The PFS rate at 36 months is calculated as the number of patients who have a progression-free survival time greater than 36 months divided by the total number of patients that started treatment. For this endpoint, we compare the PFS rate between patients who received 4 cycles of ABVD and patients who received 2 cycles of ABVD and 2 cycles of IFRT.

Secondary Outcome Measures
NameTimeMethod
Complete Response RateUp to 5 years

A Complete Response (CR) was defined as having the following conditions: 1. A complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. 2. In patients with a PET scan that was positive before therapy, a post-treatment residual mass of any size is permitted as long as it is PET-negative. A Complete Response rate was defined as the number of patients who achieved a CR divided by the number of patients that were eligible for analysis in each group. The CR rate was calculated for patients that completed 4 cycles of ABVD and for patients that completed 2 cycles of ABVD and 2 cycles of BEACOPP and IFRT.

Trial Locations

Locations (95)

Arizona Cancer Center at University of Arizona Health Sciences Center

🇺🇸

Tucson, Arizona, United States

City of Hope Comprehensive Cancer Center

🇺🇸

Duarte, California, United States

Yale Cancer Center

🇺🇸

New Haven, Connecticut, United States

CCOP - Christiana Care Health Services

🇺🇸

Newark, Delaware, United States

Lombardi Comprehensive Cancer Center at Georgetown University Medical Center

🇺🇸

Washington, District of Columbia, United States

M.D. Anderson Cancer Center at Orlando

🇺🇸

Orlando, Florida, United States

MBCCOP - Medical College of Georgia Cancer Center

🇺🇸

Augusta, Georgia, United States

Kapiolani Medical Center at Pali Momi

🇺🇸

'Aiea, Hawaii, United States

Oncare Hawaii, Incorporated - Pali Momi

🇺🇸

'Aiea, Hawaii, United States

OnCare Hawaii, Incorporated - Lusitana

🇺🇸

Honolulu, Hawaii, United States

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Arizona Cancer Center at University of Arizona Health Sciences Center
🇺🇸Tucson, Arizona, United States

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