S0816 Fludeoxyglucose F 18-PET/CT Imaging and Combination Chemotherapy With or Without Additional Chemotherapy and G-CSF in Treating Patients With Stage III or Stage IV Hodgkin Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Southwest Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00822120
First received: January 13, 2009
Last updated: February 21, 2014
Last verified: February 2014
  Purpose

RATIONALE: 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. G-CSF may help lessen the side effects in patients receiving chemotherapy. Imaging procedures, such as fludeoxyglucose F 18-PET/CT imaging, may help doctors predict how patients will respond to treatment.

PURPOSE: This phase II trial is studying fludeoxyglucose F 18-PET/CT imaging to see how well it works in assessing response to combination chemotherapy and allow doctors to plan better additional further treatment in treating patients with stage III or stage IV Hodgkin lymphoma.


Condition Intervention Phase
Lymphoma
Nonneoplastic Condition
Biological: bleomycin sulfate
Biological: filgrastim
Drug: ABVD regimen
Drug: BEACOPP regimen
Drug: cyclophosphamide
Drug: dacarbazine
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: prednisone
Drug: procarbazine hydrochloride
Drug: vinblastine sulfate
Drug: vincristine sulfate
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Response-Adapted Therapy of Stage III-IV Hodgkin Lymphoma Using Early Interim FDG-PET Imaging

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • 2-year progression-free survival (PFS) of HIV-negative patients after treatment with 2 courses of ABVD [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Measured from date of registration to date of first observation of progressive disease, or death due to any cause. Patients last known to be alive and progression-free are censored at date of last contact.

  • 2-year PFS of patients who are PET-positive after treatment with ABVD and escalated-dose BEACOPP [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Measured from date of registration to date of first observation of progressive disease, or death due to any cause. Patients last known to be alive and progression-free are censored at date of last contact.


Secondary Outcome Measures:
  • 2-year overall survival (OS) for HIV-negative patients treated with response- adapted therapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Measured from date of registration to date of death due to any cause. Patients last known to be alive and are censored at date of last contact.

  • Complete and partial response rates for HIV-negative patients treated with response- adapted therapy [ Time Frame: 7 months after registration ] [ Designated as safety issue: No ]
    Complete Response (CR) is a complete disappearance of all disease with the exception of the following. If no PET scan or when the PET scan was positive before therapy, a post-treatment residual mass of any size is permitted if it is PET negative. If the PET scan was negative before therapy, all nodal masses at baseline must have regressed. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow (BM) must be negative if positive at baseline. Normalization of markers. Partial Response (PR) is a 50% decrease in the sum of products of greatest diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes. If PET scan or when the PET scan was positive before therapy, PET should be positive in at least one previously involved site.

  • Toxicity as assessed by NCI CTCAE v3.0 [ Time Frame: Up to 7 years ] [ Designated as safety issue: Yes ]
    Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal


Estimated Enrollment: 230
Study Start Date: July 2009
Estimated Study Completion Date: April 2020
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HIV Positive, PET Negative: BEACOPP standard
Etoposide 100 mg/m2 IV Days 1, 2, 3 Dox 25 mg/m2 IV Day 1 Cyclo 650mg/m2 IV Day 1 Procarb 100 mg/m2 PO Days 1-7 Pred 40 mg/m2 PO Days 1-14 Bleo 10u/m2 IV Day 8 Vincristine 1.4 mg/m2 IV Day 8 Q 21 Days x 6 cycles
Biological: bleomycin sulfate Drug: BEACOPP regimen Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: etoposide Drug: prednisone Drug: procarbazine hydrochloride Drug: vincristine sulfate
Experimental: HIV Negative, PET Positive: BEACOPP escalated
Etoposide 200 mg/m2 IV Days 1, 2, 3 Dox 35 mg/m2 IV Day 1 Cyclo 1,250 mg/m2 IV Day 1 Procarb 100 mg/m2 PO Days 1-7 Pred 40 mg/m2 PO Days 1-14 Bleo 10u/m2 IV Day 8 Vincristine 1.4 mg/m2 IV Day 8 G-CSF 5mcg/kg/day SQ Days 8-14 Q 21 Days x 6 cycles
Biological: bleomycin sulfate Biological: filgrastim Drug: BEACOPP regimen Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: etoposide Drug: prednisone Drug: procarbazine hydrochloride Drug: vincristine sulfate
Active Comparator: HIV Positive, PET Negative: ABVD
Doxorubicin 25 mg/m2 IV Bleomycin 10u/m2 IV Vinblastine 6mg/m2 IV Dacarbazine 375 mg/m2 IV Days 1, 15 Q 28 Days x 2
Biological: bleomycin sulfate Drug: ABVD regimen Drug: dacarbazine Drug: doxorubicin hydrochloride Drug: vinblastine sulfate
Active Comparator: HIV Negative, PET Negative: ABVD
Doxorubicin 25 mg/m2 IV Bleomycin 10u/m2 IV Vinblastine 6mg/m2 IV Dacarbazine 375 mg/m2 IV Days 1, 15 Q 28 Days x 2
Biological: bleomycin sulfate Drug: ABVD regimen Drug: dacarbazine Drug: doxorubicin hydrochloride Drug: vinblastine sulfate

Detailed Description:

OBJECTIVES:

Primary

  • To estimate the 2-year progression-free survival (PFS) of HIV-negative patients with stage III-IV Hodgkin lymphoma treated with response-adapted therapy based on fludeoxyglucose F 18 (FDG)-PET imaging after 2 courses of doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine (ABVD).
  • To estimate the 2-year PFS of patients who are PET-positive after treatment with 2 courses of ABVD and an escalated dose regimen comprising cyclophosphamide, doxorubicin hydrochloride, etoposide, vincristine sulfate, bleomycin, procarbazine hydrochloride, and prednisone (BEACOPP).

Secondary

  • To estimate the 2-year overall survival (OS) of patients treated with these regimens.
  • To estimate the response rate (i.e., complete and partial responses) in patients treated with these regimens.
  • To evaluate the toxicity of these response-adapted regimens.
  • To document the feasibility of centralized, real-time review of FDG-PET imaging for U.S. cooperative group studies.
  • To prospectively evaluate the overall response rate, complete response rate, PFS, and OS of HIV-positive patients treated with these response-adapted regimens.

OUTLINE: This is a multicenter study.

All patients undergo baseline whole-body fludeoxyglucose F 18 (FDG)-PET/CT imaging before beginning chemotherapy. Patients then receive doxorubicin hydrochloride IV, bleomycin IV, vinblastine IV, and dacarbazine IV (ABVD) on days 1 and 15. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Between days 22 and 25 of course 2, patients undergo a second FDG-PET/CT scan to assess response. Subsequent therapy is based on FDG-PET/CT scan results. Patients are stratified according to FDG-PET positivity (yes vs no). Patients who are FDG-PET-negative continue treatment with ABVD for up to 4 additional courses in the absence of disease progression or unacceptable toxicity. Patients who are FDG-PET-positive are then further stratified according to HIV positivity (yes or no) and receive 1 of the following treatment regimens:

  • Escalated-dose BEACOPP chemotherapy: HIV-negative patients receive escalated-dose BEACOPP chemotherapy comprising doxorubicin hydrochloride IV and cyclophosphamide IV on day 1, etoposide IV on days 1-3, oral procarbazine hydrochloride on days 1-7, oral prednisone on days 1-14, and bleomycin IV and vincristine IV on day 8. Patients receive filgrastim (G-CSF) subcutaneously on days 8-14. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
  • Standard-dose BEACOPP chemotherapy: HIV-positive patients receive standard dose BEACOPP chemotherapy comprising doxorubicin hydrochloride IV and cyclophosphamide IV on day 1, etoposide IV on days 1-3, oral procarbazine hydrochloride on days 1-7, oral prednisone on days 1-14, and bleomycin IV and vincristine IV on day 8. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Six to eight weeks after completion of chemotherapy, patients undergo a post-treatment FDG-PET/CT scan.

Some patients may undergo bone marrow biopsy at 1 month after the last course of chemotherapy.

After completion of study treatment, patients are followed up periodically for 7 years.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed classical Hodgkin lymphoma (HL) (i.e., nodular sclerosis, mixed cellularity, lymphocyte-rich, or lymphocyte-depleted)

    • Previously untreated stage III or IV disease
    • No nodular lymphocyte predominant disease
  • Bidimensionally measurable disease
  • Adequate biopsy samples from original diagnostic specimen must be available for pathologic review

    • Tissue obtained from core biopsies allowed
    • No tissue obtained from needle aspirations or cytologies
  • Must have known HIV status

    • No multi-drug resistant HIV infection, CD4 counts < 150/μL, or other concurrent AIDS-defining conditions in HIV-positive patients
    • HIV-positive patients with CD4 counts ≥ 150/μL at the time of enrollment OR documented CD4 count > 250/μL at any time within 8 months prior to HL diagnosis allowed
  • Must have undergone unilateral or bilateral bone marrow biopsy within the past 42 days
  • Must have a diagnostic quality CT scan of the chest/abdomen and pelvis AND baseline FDG-PET scan within the past 28 days

    • Combined PET/CT scans required
    • No older "stand-alone" FDG-PET scans
    • No low-resolution "localization" CT scans as part of a combined PET/CT scans

PATIENT CHARACTERISTICS:

  • Zubrod performance status 0-2
  • Serum erythrocyte sedimentation rate, lactate dehydrogenase (LDH), hemoglobin, albumin, white blood cell count (WBC), and lymphocytes measured within the past 28 days
  • Serum estradiol (women only), testosterone (men only), follicle stimulating hormone (FSH) and luteinizing hormone (LH) (both men and women) levels must be drawn within 60 days prior to registration
  • Not pregnant or nursing
  • Fertile patients must use effective contraception during and for ≥ 6 months after completion of study therapy
  • No significant cardiac abnormalities as assessed by multiple gated acquisition scan (MUGA) or ECHO AND cardiac ejection fraction ≥ 45% in patients with a history of hypertension or cardiac symptoms
  • Hepatitis B-negative (i.e., hepatitis B surface antigen-negative or anti-hepatitis B core antigen-negative)

    • Patients immune to or immunized against hepatitis B (i.e., anti-hepatitis B surface antibody-positive) are eligible
  • Hepatitis C-negative (i.e., anti-hepatitis C antibody-negative)
  • No significant lung disease with abnormal lung function tests (i.e., diffusing capacity of lung for carbon monoxide (DLCO) > 25% below predicted after correction for hemoglobin) unless attributable to lymphoma
  • No requirement for continuous supplemental oxygen therapy
  • No other prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior chemotherapy, radiotherapy, or antibody therapy for lymphoma
  • No prior solid organ transplantation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00822120

Contacts
Contact: Megan Hardin 2106148808 ext 1014 mhardin@swog.org
Contact: Dana Sparks, MAT 2106148808 ext 1004 dsparks@swog.org

  Show 423 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Investigators
Study Chair: Oliver W. Press, MD, PhD Fred Hutchinson Cancer Research Center
  More Information

Additional Information:
No publications provided

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00822120     History of Changes
Other Study ID Numbers: CDR0000630501, S0816, U10CA032102
Study First Received: January 13, 2009
Last Updated: February 21, 2014
Health Authority: United States: Federal Government

Keywords provided by Southwest Oncology Group:
stage III adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
adult lymphocyte depletion Hodgkin lymphoma
adult lymphocyte predominant Hodgkin lymphoma
adult mixed cellularity Hodgkin lymphoma
adult nodular sclerosis Hodgkin lymphoma
HIV infection

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bleomycin
Doxorubicin
Etoposide phosphate
Cyclophosphamide
Dacarbazine
Etoposide
Prednisone
Procarbazine
Vinblastine
Vincristine
Lenograstim
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 28, 2014