Response-Based Therapy Assessed By PET Scan in Treating Patients With Bulky Stage I and Stage II Classical Hodgkin Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2015 by Alliance for Clinical Trials in Oncology
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT01118026
First received: May 5, 2010
Last updated: August 25, 2015
Last verified: August 2015

May 5, 2010
August 25, 2015
September 2010
July 2017   (final data collection date for primary outcome measure)
Progression-free survival at 36 months from enrollment [ Time Frame: Up to 36 months ] [ Designated as safety issue: No ]
Progression-free survival at 36 months from enrollment [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01118026 on ClinicalTrials.gov Archive Site
  • Complete response rate [ Time Frame: Up to 8 weeks ] [ Designated as safety issue: No ]
  • Standard uptake values (SUVs) for target sites measured at baseline, after course 2, and after completion of therapy [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Determination of the optimal cutoff for absolute decrease in maximum SUV body weight (SUVbw) and SUV lean body mass (SUVlbm), relative uptake in tumor vs various reference anatomic sites, IHP criteria as well as various cutoffs for post-therapy maxim ... [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Volumetric vs 2-dimensional (2-D) measurement changes for target lesions between baseline and after course 2, at the end of chemotherapy, and after IFRT [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Comparison of qualitative and semiquantitative fludeoxyglucose-PET findings/changes, 2-D and volumetric CT changes, and combinatorial analyses (PET + dedicated CT data) with molecular parameters and conventional parameters [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Standard uptake values (SUVs) for target sites measured at baseline, after course 2, after completion of chemotherapy, and after involved-field radiation therapy (IFRT) [ Designated as safety issue: No ]
  • Determination of the optimal cutoff for absolute decrease in maximum SUV body weight (SUVbw) and SUV lean body mass (SUVlbm), relative uptake in tumor vs various reference anatomic sites, IHP criteria as well as various cutoffs for post-therapy maxim ... [ Designated as safety issue: No ]
  • Volumetric vs 2-dimensional (2-D) measurement changes for target lesions between baseline and after course 2, at the end of chemotherapy, and after IFRT [ Designated as safety issue: No ]
  • Comparison of qualitative and semiquantitative fludeoxyglucose-PET findings/changes, 2-D and volumetric CT changes, and combinatorial analyses (PET + dedicated CT data) with molecular parameters and conventional parameters [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Response-Based Therapy Assessed By PET Scan in Treating Patients With Bulky Stage I and Stage II Classical Hodgkin Lymphoma
Phase II Trial of Response-Adapted Therapy Based on Positron Emission Tomography (PET) for Bulky Stage I and Stage II Classical Hodgkin Lymphoma (HL)

This research is being done in order to improve treatment outcomes in patients diagnosed with bulky, early stage Hodgkin lymphoma and to reduce the side effects that are associated with use of radiation used in current treatments. The chemotherapy treatment in this study consists of a combination of four drugs approved by the Food and Drug Administration (FDA): doxorubicin, bleomycin, vinblastine, and dacarbazine. This regimen (called ABVD) has been found to be effective in treating patients with Hodgkin lymphoma and is considered the standard of treatment used with radiation therapy in patients with bulky early stage Hodgkin lymphoma. As part of the evaluation of the effectiveness of the chemotherapy treatment, PET scans will be obtained during the course of therapy. The usefulness of this PET scan will be evaluated to determine whether radiation may be left out in the treatment of disease if the PET scan shows that the patient has responded to chemotherapy alone. The plan is to identify a group of patients using early PET scans in order to change to a chemotherapy treatment called BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone). It is one of the most highly effective chemotherapy regimens for Hodgkin lymphoma, but is associated with more side effects than ABVD. Although it has become standard of care in Europe, its use has been more limited in the U.S. because of concerns about toxicity.

This is single-arm phase II clinical trial of response-adapted therapy based on PET for bulky stage I and stage II Hodgkin lymphoma. A maximum of 123 patients will be entered to the study. The primary outcome of this study is progression-free survival (PFS), defined as the time from study entry to disease progression or death.

Primary Objective:

To determine the progression-free survival (PFS) at 36 months from enrollment for patients with bulky stage I and II Hodgkin lymphoma. All patients will begin treatment with ABVD. Patients who are PET negative after 2 cycles of chemotherapy will receive 6 cycles of ABVD without radiotherapy. Patients who are PET positive after 2 cycles of ABVD will then receive 4 cycles of escalated BEACOPP followed by IFRT. A comparison will be made of the 36-month PFS between patients who are PET positive and those who are PET negative following 2 cycles of ABVD.

Secondary Objectives:

  1. To evaluate the complete response (CR) rate of patients diagnosed with bulky stage I and II Hodgkin lymphoma following PET response-adapted chemotherapy with or without radiation therapy.
  2. To determine the predictive value of FDG uptake using various semiquantitative approaches, at baseline, after 2 cycles of ABVD and at completion of therapy.
  3. To determine the predictive value of volumetric vs. 2 dimensional (2-D) measurement changes on CT between baseline and after 2 cycles, at the end of chemotherapy (PET negative patients only) and after RT (PET positive patients only) and compare with PET parameters.
  4. To determine if changes in both qualitative and semiquantitative FDG-PET findings between baseline and after cycle 2, at end of chemotherapy (PET negative patients only) and after RT (PET positive patients only) with combination analyses with incorporating changes obtained from dedicated CT scans, correlate with response and PFS.
  5. To compare the predictive value of both qualitative and semiquantitative FDG-PET changes, 2-D and volumetric CT changes, and combinatorial analyses (PET+dedicated CT data) with molecular parameters, and conventional parameters, including IPS.
  6. To assess whether elevated baseline serum soluble CD30 (sCD30), IL10, CCL17, and CCL22 correlate with clinical response and PFS.
  7. To assess whether persistent or recurrent elevation of serial serum sCD30, IL10, CCL17, or CCL22 correlate with relapse/progression or PET scan results.
  8. To confirm independently useful tissue biomarkers (bcl-2, MAL, FOXP3, CD68, GzB) for risk stratification in patients with bulky stage I and II Hodgkin lymphoma treated with this regimen.
  9. To compare mediastinal bulk on standing PA and lateral chest x-ray (> 0.33 maximum chest diameter) with chest CT (mass > 10 cm).

After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 2-3 years, and then once a year for a maximum of ten years from the time of entry on the study.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Lymphoma
  • Drug: ABVD
    doxorubicin 25 mg/m^2 IV bleomycin 10 units/m^2 IV vinblastine 6 mg/m^2 IV dacarbazine 375 mg/m^2 IV
  • Drug: BEACOPP
    bleomycin 10 units/m^2 IV on Day 8 etoposide 200 mg/m^2 IV on Days 1, 2 and 3 doxorubicin 35 mg/m^2 IV on Day 1 cyclophosphamide 1250 mg/m^2 IV on Day 1 vincristine 1.4 mg/m^2 IV on Day 8 procarbazine 100 mg/m^2 orally on Days 1-7 prednisone 40 mg/m^2 orally on Days 1-14
  • Radiation: radiation therapy
Experimental: ABVD +/- BEACOPP + radiation

Patients receive ABVD administered by intravenous (IV) infusion on days 1 and 15 of each cycle. A cycle is considered 28 days. Patients receive a total of two cycles.

Patients undergo a PET scan following two cycles of ABVD. If the PET scan is negative, then the patient will receive four more cycles of ABVD (a total of 6 cycles of ABVD). If the PET scan is positive, then the patient receives four cycles of escalated BEACOPP for 21 days (a total of 4 cycles).

3-6 weeks after BEACOPP therapy, patients receive radiation therapy for 5 days per week (a total of 3.5 weeks).

All patients will be followed for a maximum of ten years.

Interventions:
  • Drug: ABVD
  • Drug: BEACOPP
  • Radiation: radiation therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
123
Not Provided
July 2017   (final data collection date for primary outcome measure)
  1. Documentation of Disease:

    • Histologically documented Hodgkin lymphoma subclassified according to the WHO modification of the Rye Classification and staged according to the modified Ann Arbor Staging Classification system.

      • Patients must have clinical stage IA, IB, IIA or IIB.
      • Patients with "E" extensions will be eligible if all other criteria have been met.
      • Nodular lymphocyte predominant Hodgkin lymphoma is excluded.
      • Core needle biopsies are acceptable if they contain adequate tissue for primary diagnosis and immunophenotyping. Fine needle aspirates are not acceptable. If multiple specimens are available, please submit the most recent. Failure to submit pathology materials within 60 days of patient registration will be considered a major protocol violation.
    • Patients must have a mediastinal mass > 0.33 maximum intrathoracic diameter on standing postero-anterior chest x-ray or mass measuring > 10 cm in its largest diameter.
  2. Second Malignancy: No "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.
  3. Prior Therapy - Patients may have had one cycle only of ABVD prior to enrolling on study. No other prior treatment (chemotherapy or radiation therapy) for Hodgkin lymphoma is allowed. If patient has had one cycle of ABVD, in order to be eligible to enroll on CALGB 50801, the patient must have had all of the following tests prior to starting the first cycle of ABVD:

    • LVEF by ECHO or MUGA
    • PFTs (including DLCO/FVC)CT scan (neck*, chest, abdomen, pelvis)
    • FDG-PET/CT scan
    • Chest X-ray, PA & Lateral
    • CBC, differential, platelets
    • ESR
    • Serum creatinine
    • Glucose
    • AST
    • Alkaline phosphatase
    • Bilirubin
    • LDH

    Patients with a negative FDG-PET/CT scan do not need to have had a dedicated neck CT scan prior to starting the previous cycle of ABVD.

  4. ECOG Performance status 0-2.
  5. LVEF and DLCO - LVEF by ECHO or MUGA within institutional normal limits unless thought to be disease related. DLCO ≥ 60% with no symptomatic pulmonary disease unless thought to be disease related.
  6. HIV Infection - Patients with known HIV must have a CD4 count > 350 and be on concurrent antiretrovirals. 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. An HIV test is not required for entry on this protocol, but is required if the patient is perceived to be at risk.
  7. Pregnancy Restrictions - Non-pregnant and non-nursing. Due to the teratogenic potential of the agents used in this study, pregnant or nursing women may not be enrolled. Women and men of reproductive potential should agree to use an effective means of birth control.
  8. Age Restricitions - Age 18 - 60 years
  9. Initial Required Laboratory Data:

    • ANC ≥ 1000/μL
    • Platelet count ≥ 100,000/μL
    • Serum Creatinine ≤ 2 mg/dL
    • Bilirubin* ≤ 2 x upper limit of normal
    • AST ≤ 2 x upper limit of normal* - In the absence of Gilbert's disease
Both
18 Years to 60 Years
No
Contact: Ann S. LaCasce, MD 617 632-5959
United States
 
NCT01118026
CALGB-50801, CDR0000669076, NCI-2011-02034
No
Alliance for Clinical Trials in Oncology
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Study Chair: Ann S. LaCasce, MD Dana-Farber Cancer Institute
Alliance for Clinical Trials in Oncology
August 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP