Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Sclerosis

Lymphoma

Hodgkin Disease

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Hodgkin Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Anti-Inflammatory Agents

Etoposide

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Prednisone

Vincristine

Etoposide phosphate

Bleomycin

Vinblastine

Dacarbazine

Procarbazine

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.

doxorubicin 25 mg/m\^2 IV bleomycin 10 units/m\^2 IV vinblastine 6 mg/m\^2 IV dacarbazine 375 mg/m\^2 IV

ABVD

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

BEACOPP

radiation therapy

Ann S. LaCasce, MD

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.

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)

Progression-free survival (PFS) is defined as the time from first PET/CT scan to disease progression or death. Patients who are alive without disease progression will be censored at the time of their most recent disease evaluation. The Kaplan-Meier three-year (36 month) survival estimates and confidence intervals are presented below.

A Complete Response (CR) is defined as the complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. For this endpoint, the best response at any time post-baseline was analyzed

National Cancer Institute (NCI)

Alliance for Clinical Trials in Oncology

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.\>

\> 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\>

\> 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 therapy

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

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). \>

\>

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

\> 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

ABVD (PET-negative)

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 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.\>

\> 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\>

\> 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 therapy

ABVD + BEACOPP + Radiation (PET-positive)

Six patients were not eligible for this analysis and one patient was not evaluated for PET status screening. All patients that were eligible and evaluated for PET screening were included in this analysis.

Progression-free Survival at 36 Months

All eligible patients patients who were screened for PET status and were evaluated for response are included in this analysis.

Complete Response

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

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

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 ...

Standard Uptake Values (SUVs) for Target Sites Measured at Baseline, After Course 2, and After Completion of Therapy

Overall Study

Recurrence

Vorinostat

Histone Deacetylase Inhibitors

Enzyme Inhibitors

Patients receive oral vorinostat twice daily on days 1-14. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 2 additional courses of therapy beyond CR.

vorinostat

laboratory biomarker analysis

Mark Kirschbaum

This phase II trial is studying how well vorinostat works in treating patients with relapsed or refractory advanced Hodgkin's lymphoma. Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To evaluate the response probability (complete, complete unconfirmed, and partial) in patients with relapsed or refractory Hodgkin's lymphoma.

II. To estimate 1-year progression-free survival and overall survival in patients with relapsed or refractory Hodgkin's lymphoma treated with SAHA.

III. To assess the toxicity profile of SAHA in this patient population. IV. To perform gene expression profiling on tumor tissue before and after treatment in order to explore in a preliminary manner the association between response and specific gene expression results.

OUTLINE: This is a multicenter study.

Patients receive oral vorinostat twice daily on days 1-14. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 2 additional courses of therapy beyond CR.

After completion of study treatment, patients are followed every 6 months for 2 years and then annually for 3 years.

Vorinostat in Treating Patients With Relapsed or Refractory Advanced Hodgkin's Lymphoma

A Phase II Trial of Suberoylanilide Hydroxamic Acid (NSC-701852) for Recurrent or Primary Refractory Hodgkin's Lymphoma

Complete Response(CR) is a complete disappearance of all disease with the exception of nodes. 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. CR Unconfirmed (CRU) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM. Partial Response(PR) is a 50% decrease in the 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.

Measured from date of registration to date of first observation of progression or death, or last contact date. Progression is defined as a 50% increase in sum of products of greatest diameters (SPD) of target measurable lesions over the smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline; appearance of a new lesion/site; unequivocal progression of non-measurable disease in the opinion of the treating physician; death due to disease without prior documentation of progression.

Measured from date of registration to death, or last contact date

SAHA (Vorinostat)

Patients receive vorinostat 400 mg/day on days 1-14 of every 21-day cycle. Patients continue treatment until progression.

Race (NIH/OMB)

Study Statistician

Complete Response (CR)

Partial Response (PR)

Unconfirmed Complete Response (UCR)

Unconfirmed Partial Response (UPR)

No Response

All patients who started treatment were included in assessing response estimates.

Assess Number of Patients Who Achieve Confirmed and Unconfirmed Complete Response (CR) or Partial Response (PR)

All eligible patients who started treatment were included in assessing progression-free survival.

Progression-Free Survival

All eligible patients who started treatment were included in assessing overall survival.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Response-Based Therapy Assessed By PET Scan in Treating Patients With Bulky Stage I and Stage II Classical Hodgkin Lymphoma	NCT01118026	Lymphoma	ABVD BEACOPP radiation thera...	18 Years - 60 Years	Alliance for Clinical Trials in Oncology
Vorinostat in Treating Patients With Relapsed or Refractory Advanced Hodgkin's Lymphoma	NCT00132028	Adult Favorable... Adult Lymphocyt... Adult Lymphocyt... Adult Mixed Cel... Adult Nodular L... Adult Nodular S... Adult Unfavorab... Recurrent Adult...	vorinostat laboratory biom...	18 Years -	National Cancer Institute (NCI)
Vorinostat in Treating Patients With Relapsed or Refractory Advanced Hodgkin's Lymphoma	NCT00132028	Adult Favorable... Adult Lymphocyt... Adult Lymphocyt... Adult Mixed Cel... Adult Nodular L... Adult Nodular S... Adult Unfavorab... Recurrent Adult...	vorinostat laboratory biom...	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for adult favorable prognosis hodgkin lymphoma