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Chemotherapy Plus Radiation Therapy in Treating Patients With Refractory or Relapsed Hodgkin's Lymphoma

High-Dose Chemo-Radiotherapy for Patients With Primary Refractory and Relapsed Hodgkin's Disease

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00003631
Enrollment
118
Registered
2003-01-27
Start date
1998-08-31
Completion date
Unknown
Last updated
2016-01-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lymphoma

Keywords

recurrent adult Hodgkin lymphoma, recurrent/refractory childhood Hodgkin lymphoma

Brief summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy used to kill tumor cells. PURPOSE: Phase II trial to study the effectiveness of chemotherapy plus radiation therapy in treating patients with refractory or relapsed Hodgkin's lymphoma.

Detailed description

OBJECTIVES: * Assess the efficacy of a high-dose chemoradiotherapy regimen in patients with refractory or relapsed Hodgkin's lymphoma. OUTLINE: Patients are stratified into 1 of 3 treatment arms (0-1 adverse prognostic factors vs 2 adverse prognostic factors vs 3 adverse prognostic factors). * Arm I (0-1 adverse prognostic factors): Patients receive ifosfamide by 24 hour infusion on day 2. Carboplatin is administered on day 2. Etoposide IV is administered once daily on days 1-3. Patients then receive filgrastim (G-CSF) subcutaneously or IV on days 5-12. Patients receive another course of ICE chemotherapy 2-3 weeks after the first course. Leukapheresis is performed once WBC reaches at least 3000/mm\^3 and continues until enough peripheral blood stem cells are collected. Patients who have never received prior radiotherapy will receive accelerated hyperfractionated total lymphoid irradiation (TLI) twice a day for 5 days (days -10 to -6). Cyclophosphamide IV is then administered on days -5 and 4. Etoposide IV is administered by continuous infusion over 4 days (days -5 to -2). Patients who have had prior radiotherapy receive high dose chemotherapy. Cyclophosphamide IV is administered on days -6 and -5. Etoposide IV is administered by continuous infusion over 4 days (days -6 to -3). Carmustine IV is administered on day -2. Peripheral blood stem cells are infused 24-36 hours after high-dose chemotherapy. G-CSF is administered beginning on day 1 and continuing until blood counts recover. * Arm II (2 adverse prognostic factors): Patients receive the first course of ICE as in Arm I. Apheresis is performed once WBC is greater than 3000/mm\^3 and continues until enough cells are collected. The second course of ICE is then administered. Ifosfamide is administered by 48 hour continuous infusion on days 1-2. Carboplatin is administered on day 3. Etoposide IV is administered every 12 hours for 3 doses beginning on day 1. Patients receive G-CSF on days 5-14. Patients who have never received prior radiotherapy will receive accelerated hyperfractionated TLI for 5 days (days -10 to -6). Cyclophosphamide IV is then administered every 12 hours on days -5 to -2. Etoposide IV is administered by continuous infusion over 4 days (days -5 to -2). Patients who have had prior radiotherapy receive high-dose chemotherapy. Cyclophosphamide IV is administered every 12 hours on days -6 to -3. Etoposide IV is administered by continuous infusion over 4 days (days -6 to -3). Carmustine IV is administered on day -2. Peripheral blood stem cells are infused 24-36 hours after high dose chemotherapy. G-CSF is administered beginning on day 1 and continuing until blood counts recover. * Arm III (3 adverse prognostic factors): Patients receive cyclophosphamide IV daily for 2 days, then G-CSF beginning on day 4 until blood stem cells are collected. Patients then undergo apheresis until enough cells are collected. Patients receive high-dose chemotherapy. Ifosfamide IV is administered for 1 hour. Etoposide is administered by continuous infusion for 12 hours. Carboplatin IV is administered for 1 hour. Etoposide is again administered by continuous infusion for 12 hours. Treatment is repeated daily for 5 days. Peripheral blood stem cells are reinfused 24-36 hours after the last dose of chemotherapy. G-CSF is administered beginning on day 1 and continuing until blood counts recover. Patients who have never received prior radiation will now receive accelerated hyperfractionated TLI twice daily for 5 days. Patients receive a second course of high dose chemotherapy 45-90 days after reinfusion of cells. Etoposide IV and cytarabine IV are administered every 12 hours for 4 days (days -6 to -3). Melphalan IV is administered on day -2. Patients who have received prior radiation therapy receive a second course of high-dose chemotherapy. Carmustine IV is administered on day -7. Etoposide IV and cytarabine IV are administered every 12 hours for 4 days (days -6 to -3). Melphalan IV is administered on day -2. Peripheral blood stem cells are reinfused 24-48 hours after completion of second course chemotherapy. G-CSF is administered beginning on day 1 and continuing until blood counts recover. Patients are followed every 3 months for the first 2 years, every 4 months during years 3-5, and every 6 months thereafter. PROJECTED ACCRUAL: This study will accrue 80 patients within 4 years.

Interventions

BIOLOGICALfilgrastim
DRUGcarboplatin
DRUGcarmustine
DRUGcyclophosphamide
DRUGcytarabine
DRUGetoposide
DRUGifosfamide
DRUGmelphalan
PROCEDUREbone marrow ablation with stem cell support
PROCEDUREperipheral blood stem cell transplantation
RADIATIONradiation therapy

Sponsors

National Cancer Institute (NCI)
CollaboratorNIH
Memorial Sloan Kettering Cancer Center
Lead SponsorOTHER

Study design

Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
No minimum to 120 Years
Healthy volunteers
No

Inclusion criteria

DISEASE CHARACTERISTICS: * Histologically confirmed residual or relapsed Hodgkin's lymphoma following conventional dose standard chemotherapy * Presence of the following prognostic factors are allowed: * B symptoms (fever, weight loss, night sweats) * Extranodal disease * Complete remission of less than 1 year duration PATIENT CHARACTERISTICS: Age: * Not specified Performance status: * Not specified Life expectancy: * Not specified Hematopoietic: * Not specified Hepatic: * Bilirubin less than 2.0 mg/dL unless history of Gilbert's disease * No chronic active or persistent hepatitis Renal: * No history of chronic renal insufficiency * Creatinine no greater than 1.5 mg/dL OR * Creatinine clearance at least 60 mL/min Cardiovascular: * No myocardial infarction within the past 6 months * No unstable angina * No significant cardiac arrhythmias other than chronic atrial fibrillation * Ejection fraction at least 50% Pulmonary: * DLCO at least 50% Other: * No uncontrolled infection * HIV negative * At least 5 years since prior malignancy except: * Curatively treated cutaneous basal cell carcinoma * Carcinoma in situ of the cervix * Not pregnant or nursing * Fertile women must use effective contraception PRIOR CONCURRENT THERAPY: * Must have failed conventional dose standard chemotherapy

Design outcomes

Primary

MeasureTime frameDescription
Objective Response2 yearsDetermine the overall objective response. CR rate \[as measured from the start of ICE, (or high dose CTX) to the end of transplant for those who receive it, or the end of ICE for those who do not\].Complete response (CR): No evidence of Hodgkin's disease determined clinically, radiologically or pathologically when indicated

Countries

United States

Participant flow

Participants by arm

ArmCount
Group A - Favorable Prognostic Group50
Group B - Intermediate Prognostic Group44
Group C - Unfavorable Prognostic Group24
Total118

Withdrawals & dropouts

PeriodReasonFG000FG001FG002
Overall StudyAdverse Event115
Overall StudyDeath001
Overall StudyEvaluable for toxicity only002
Overall StudyPatient not treated101
Overall StudyProtocol Violation100

Baseline characteristics

CharacteristicGroup A - Favorable Prognostic GroupGroup B - Intermediate Prognostic GroupGroup C - Unfavorable Prognostic GroupTotal
Age, Categorical
<=18 years
0 Participants1 Participants1 Participants2 Participants
Age, Categorical
>=65 years
1 Participants0 Participants0 Participants1 Participants
Age, Categorical
Between 18 and 65 years
49 Participants43 Participants23 Participants115 Participants
Sex: Female, Male
Female
24 Participants24 Participants10 Participants58 Participants
Sex: Female, Male
Male
26 Participants20 Participants14 Participants60 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —
other
Total, other adverse events
50 / 5044 / 4423 / 24
serious
Total, serious adverse events
2 / 506 / 445 / 24

Outcome results

Primary

Objective Response

Determine the overall objective response. CR rate \[as measured from the start of ICE, (or high dose CTX) to the end of transplant for those who receive it, or the end of ICE for those who do not\].Complete response (CR): No evidence of Hodgkin's disease determined clinically, radiologically or pathologically when indicated

Time frame: 2 years

ArmMeasureGroupValue (NUMBER)
Group A - Favorable Prognostic GroupObjective ResponseFailure3 participants
Group A - Favorable Prognostic GroupObjective ResponseMinor Response (MR)2 participants
Group A - Favorable Prognostic GroupObjective ResponsePartial Response (PR)1 participants
Group A - Favorable Prognostic GroupObjective ResponseProgression Free (P-Free)41 participants
Group A - Favorable Prognostic GroupObjective ResponseComplete Response (CR)0 participants
Group A - Favorable Prognostic GroupObjective ResponseProgression of Disease (POD)0 participants
Group B - Intermediate Prognostic GroupObjective ResponseProgression of Disease (POD)1 participants
Group B - Intermediate Prognostic GroupObjective ResponseFailure6 participants
Group B - Intermediate Prognostic GroupObjective ResponseProgression Free (P-Free)31 participants
Group B - Intermediate Prognostic GroupObjective ResponseComplete Response (CR)2 participants
Group B - Intermediate Prognostic GroupObjective ResponseMinor Response (MR)1 participants
Group B - Intermediate Prognostic GroupObjective ResponsePartial Response (PR)2 participants
Group C - Unfavorable Prognostic GroupObjective ResponseMinor Response (MR)0 participants
Group C - Unfavorable Prognostic GroupObjective ResponsePartial Response (PR)4 participants
Group C - Unfavorable Prognostic GroupObjective ResponseProgression of Disease (POD)0 participants
Group C - Unfavorable Prognostic GroupObjective ResponseProgression Free (P-Free)7 participants
Group C - Unfavorable Prognostic GroupObjective ResponseFailure3 participants
Group C - Unfavorable Prognostic GroupObjective ResponseComplete Response (CR)1 participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026