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| ID | Type | Description | Link |
|---|---|---|---|
| CDR0000066714 | Registry Identifier | PDQ (Physician Data Query) | |
| NCI-G98-1480 |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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.
OBJECTIVES:
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).
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.
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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm I | Experimental | (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. |
|
| Arm II | Experimental | (2 adverse prognostic factors): Patients receive the first course of ICE as in Arm I |
|
| Arm III | Experimental | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| filgrastim | Biological |
| ||
| carboplatin |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 2 years |
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DISEASE CHARACTERISTICS:
Histologically confirmed residual or relapsed Hodgkin's lymphoma following conventional dose standard chemotherapy
Presence of the following prognostic factors are allowed:
PATIENT CHARACTERISTICS:
Age:
Performance status:
Life expectancy:
Hematopoietic:
Hepatic:
Renal:
Cardiovascular:
Pulmonary:
Other:
No uncontrolled infection
HIV negative
At least 5 years since prior malignancy except:
Not pregnant or nursing
Fertile women must use effective contraception
PRIOR CONCURRENT THERAPY:
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| Name | Affiliation | Role |
|---|---|---|
| Joachim Yahalom, MD | Memorial Sloan Kettering Cancer Center | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Memorial Sloan-Kettering Cancer Center | New York | New York | 10021 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Group A - Favorable Prognostic Group | |
| FG001 | Group B - Intermediate Prognostic Group | |
| FG002 | Group C - Unfavorable Prognostic Group |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Drug |
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| carmustine | Drug |
|
| cyclophosphamide | Drug |
|
| cytarabine | Drug |
|
| etoposide | Drug |
|
| ifosfamide | Drug |
|
| melphalan | Drug |
|
| bone marrow ablation with stem cell support | Procedure |
|
| peripheral blood stem cell transplantation | Procedure |
|
| radiation therapy | Radiation |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Group A - Favorable Prognostic Group | |
| BG001 | Group B - Intermediate Prognostic Group | |
| BG002 | Group C - Unfavorable Prognostic Group | |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | Posted | Number | participants | 2 years |
|
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|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Group A - Favorable Prognostic Group | 2 | 50 | 50 | 50 | |||
| EG001 | Group B - Intermediate Prognostic Group | 6 | 44 | 44 | 44 | |||
| EG002 | Group C - Unfavorable Prognostic Group | 5 | 24 | 23 | 24 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac ischemia | Cardiac disorders | CTC-2.0 | Systematic Assessment |
| |
| Catheter related infection | Infections and infestations | CTC-2.0 | Systematic Assessment |
| |
| Pneumonitis | General disorders | CTC-2.0 | Systematic Assessment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTC-2.0 | Systematic Assessment |
| |
| Febrile neutropenia | General disorders | CTC-2.0 | Systematic Assessment |
| |
| Infection without neutropenia | Infections and infestations | CTC-2.0 | Systematic Assessment |
| |
| Neutrophils | Blood and lymphatic system disorders | CTC-2.0 | Systematic Assessment |
| |
| Pulmonary, other | Respiratory, thoracic and mediastinal disorders | CTC-2.0 | Systematic Assessment |
| |
| Supravent arrhythmia | Cardiac disorders | CTC-2.0 | Systematic Assessment |
| |
| Confusion | Nervous system disorders | CTC-2.0 | Systematic Assessment |
| |
| GI, other | General disorders | CTC-2.0 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | CTC-2.0 | Systematic Assessment |
| |
| Typhlitis | Gastrointestinal disorders | CTC-2.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Alkaline phosphatase | Metabolism and nutrition disorders | CTC-2.0 | Systematic Assessment |
| |
| Bilirubin | Metabolism and nutrition disorders | CTC-2.0 | Systematic Assessment |
| |
| Hemoglobin (Hgb) | Blood and lymphatic system disorders | CTC-2.0 | Systematic Assessment |
| |
| Hyperglycemia | Metabolism and nutrition disorders | CTC-2.0 | Systematic Assessment |
| |
| Hyperkalemia | Metabolism and nutrition disorders | CTC-2.0 | Systematic Assessment |
| |
| Hypocalcemia | Metabolism and nutrition disorders | CTC-2.0 | Systematic Assessment |
| |
| Hypokalemia | Metabolism and nutrition disorders | CTC-2.0 | Systematic Assessment |
| |
| Hyponatremia | Metabolism and nutrition disorders | CTC-2.0 | Systematic Assessment |
| |
| Hypophosphatemia | Metabolism and nutrition disorders | CTC-2.0 | Systematic Assessment |
| |
| Leukocytes | Blood and lymphatic system disorders | CTC-2.0 | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | CTC-2.0 | Systematic Assessment |
| |
| Neutrophils | Blood and lymphatic system disorders | CTC-2.0 | Systematic Assessment |
| |
| Platelets | Blood and lymphatic system disorders | CTC-2.0 | Systematic Assessment |
| |
| Pneumonitis | Gastrointestinal disorders | CTC-2.0 | Systematic Assessment |
| |
| Prothrombin time (PT) | Blood and lymphatic system disorders | CTC-2.0 | Systematic Assessment |
| |
| Partial thromboplastin time (PTT) | Blood and lymphatic system disorders | CTC-2.0 | Systematic Assessment |
| |
| SGOT (AST) | Blood and lymphatic system disorders | CTC-2.0 | Systematic Assessment |
| |
| SGPT (ALT) | Blood and lymphatic system disorders | CTC-2.0 | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Joachim Yahalom | Memorial Sloan Kettering Cancer Center | 1212-639-5999 | yahalomj@mskcc.org |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D006689 | Hodgkin Disease |
| D012008 | Recurrence |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000069585 | Filgrastim |
| D016190 | Carboplatin |
| D002330 | Carmustine |
| D003520 | Cyclophosphamide |
| D003561 | Cytarabine |
| D005047 | Etoposide |
| D007069 | Ifosfamide |
| D008558 | Melphalan |
| D036102 | Peripheral Blood Stem Cell Transplantation |
| D011878 | Radiotherapy |
| ID | Term |
|---|---|
| D016179 | Granulocyte Colony-Stimulating Factor |
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D016298 | Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D009607 | Nitrosourea Compounds |
| D014508 | Urea |
| D000577 | Amides |
| D009603 | Nitroso Compounds |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001087 | Arabinonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D011034 | Podophyllotoxin |
| D013764 | Tetrahydronaphthalenes |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D011083 | Polycyclic Compounds |
| D005960 | Glucosides |
| D006027 | Glycosides |
| D010078 | Oxazines |
| D010649 | Phenylalanine |
| D024322 | Amino Acids, Aromatic |
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D018380 | Hematopoietic Stem Cell Transplantation |
| D033581 | Stem Cell Transplantation |
| D017690 | Cell Transplantation |
| D064987 | Cell- and Tissue-Based Therapy |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D014180 | Transplantation |
| D013514 | Surgical Procedures, Operative |
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| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Title | Measurements |
|---|---|
|
| Partial Response (PR) |
|
| Progression Free (P-Free) |
|
| Complete Response (CR) |
|
| Progression of Disease (POD) |
|