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| ID | Type | Description | Link |
|---|---|---|---|
| P30CA033572 | U.S. NIH Grant/Contract | View source | |
| CHNMC-99067 | |||
| CDR0000589621 | Registry Identifier | NCI PDQ | |
| NCI-2010-00431 | Registry Identifier | NCI CTRP |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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RATIONALE: Giving high-dose chemotherapy drugs, such as carmustine, etoposide, and cyclophosphamide, before a peripheral blood stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. After treatment, stem cells that were collected from the patient's blood are returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.
PURPOSE: This clinical trial is studying the side effects of giving high-dose carmustine, etoposide, and cyclophosphamide together with a stem cell transplant and to see how well it works in treating patients with HIV-associated lymphoma.
OBJECTIVES:
Primary
OUTLINE: Patients undergo leukapheresis to obtain peripheral blood stem cells (PBSCs) for transplantation. At least 5 days later, patients with an adequate number of collected cells proceed to high-dose chemotherapy.
After completion of study treatment, patients are followed at approximately 30 days and 100 days, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (high-dose chemotherapy, anti-HIV therapy) | Experimental | Patients undergo leukapheresis to obtain PBSCs for transplantation. At least 5 days later, patients with an adequate number of collected cells proceed to high-dose chemotherapy. Patients receive carmustine IV over 4 hours on days -7 to -5, etoposide IV over 4 hours on day -4, and cyclophosphamide IV on day -2. Patients receive an autologous PBSC infusion on day 0. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| carmustine | Drug | 150 mg/m2 day -7, -6,and -5 prior to stem cell reinfusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of days to engraftment as defined by the standard operating procedures of the department of biostatistics at the City of Hope | Day 100 post stem cell reinfusion | |
| Feasibility and treatment-associated toxicity of this regimen | 1 year post stem cell reinfusion |
| Measure | Description | Time Frame |
|---|---|---|
| Ability to mobilize adequate numbers of peripheral blood stem cells (2.5 x 10e6 CD34+cells) | At the completion of stem cell collection | |
| Disease-free and overall survival | 2 years post stem cell reinfusion |
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Inclusion Criteria:
HIV seropositive at or before the time of lymphoma diagnosis
Subjects must be on a multi-drug regimen (excluding azidothymidine) to maintain HIV viral load less than 50,000 Gc/mL; if the CD4 count at enrollment is less than 100 then the viral load should be less than 10,000 by reverse transcriptase polymerase chain reaction (Rt-PCR); if the CD4 count is greater than 100/mm^3 prior to the start of any lymphoma chemotherapy and is greater than 100/mm^3 for at least 3 months then the viral load must be less than 150,000 gc/ml and clinically stable; if no pre-chemotherapy CD4 counts are available, then viral load alone will be used from enrollment
The known hematopoietic toxicity of AZT (zidovudine) prohibits its use pre-transplant during stem cell collection and during the immediate period of engraftment post-transplant; resumptions of AZT should not begin until there is evidence of stable engraftment; therefore, AZT should not be resumed until at least 2 months after last blood product support is used; since platelet support continues until approximately day +14 days in our experience with acquired immune deficiency syndrome (AIDS) patients transplanted date, AZT will be prohibited until at least 2 months after transplant; therefore, if the anti-HIV drug combination needs to be modified then AZT can be part of the new regimen
Karnofsky performance status >= 70%
Biopsy proven intermediate grade or high-grade Non-Hodgkin's lymphoma, (working formulation groups D-H and J, and Plasmablastic lymphoma of any disease state, including first remission given the poor risk nature of this histology) or Hodgkin's lymphoma of any subtype except nodular lymphocytic and histiocytic (L&H) lymphocyte predominant; tissue histology will be reviewed at the City of Hope
Patients with prior marrow involvement must demonstrate < 10% involvement (by morphology) pre stem cell collection
Pretreatment serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvate transaminase (SGPT) < 1.5 x institutional upper limit of normal
Serum bilirubin < 1.5 x institutional upper limit of normal
Patients who are Hepatitis C antibody positive or Hepatitis B surface antigen positive without clinical evidence of cirrhosis will be eligible after further evaluation; specifically, if patient hepatitis C or B positive viral loads will be measured; patients with hepatitis B and ongoing evidence of viral replication may require therapy prior to receiving high dose chemotherapy; this decision will be at the discretion of the treating physician
Serum creatinine < 2 x institutional upper limit of normal and a 24 hour urine creatinine clearance > 60 cc/min
Prothrombin time (PT)/partial thromboplastin time (PTT) < 2 x normal
Forced expiratory volume in one second (FEV1) or diffusing capacity of the lung for carbon monoxide (DLCO) >= 50% predicted
Left ventricular ejection fraction (LVEF) >= 50% (by 2 dimensional [2 D] echocardiogram or multi gated acquisition scan [MUGA] scan); absence of cardiomyopathy, congestive heart failure or dysrhythmia
If female of child bearing potential, must have negative serum pregnancy test
Subjects must be on a prophylactic regimen for pneumocystis pneumonia if the CD4 counts are < 200
Subjects who are not in complete remission must have measurable disease; measurable disease means that there are bidimensionally measurable lesions with clearly defined margins using either a medical photograph, computerized axial tomography (CAT) scan or magnetic resonance imaging (MRI) scan, or palpation of lesions with both diameters >= 2 cm; evaluable disease means that the lesions are only unidimensionally measurable, or have indistinct margins or have both diameters < 0.5 cm, or that the palpable lesions have a diameter < 2.0 cm, or are lesions in bone; pleural effusions and ascites are considered nonevaluable disease; scans must be within 28 days from enrollment
A minimum of 2.5 x 10^6 CD34 cells/kg must have been collected
Hodgkin's Lymphoma:
Non-Hodgkin's Lymphoma:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Amrita Y. Krishnan, MD | City of Hope Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| City of Hope Medical Center | Duarte | California | 91010-3000 | United States |
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| cyclophosphamide | Drug | 100 mg/kg on day -2 prior to stem cell reinfusion |
|
| etoposide | Drug | 60 mg/kg on day -4 prior to stem cell reinfusion |
|
| pharmacological study | Other | Prior to start of etoposide infusion, 2 hours after start of infusion, just prior to the end of infusion, then at 0.5, 1, 2, 4, 24 and 48 hours after the end of infusion |
|
| autologous hematopoietic stem cell transplantation | Procedure | Reinfusion of autologous stem cells |
|
| peripheral blood stem cell transplantation | Procedure | Reinfusion of autologous stem cells |
|
| HIV viral load, CD4+/CD8+ counts, and immune recovery | 2 years post stem cell reinfusion |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D006689 | Hodgkin Disease |
| D020522 | Lymphoma, Mantle-Cell |
| D012008 | Recurrence |
| D054218 | Precursor T-Cell Lymphoblastic Leukemia-Lymphoma |
| D016410 | Lymphoma, T-Cell, Cutaneous |
| D002051 | Burkitt Lymphoma |
| D016403 | Lymphoma, Large B-Cell, Diffuse |
| D008228 | Lymphoma, Non-Hodgkin |
| D008224 | Lymphoma, Follicular |
| D016400 | Lymphoma, Large-Cell, Immunoblastic |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| 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 |
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D006402 | Hematologic Diseases |
| D016399 | Lymphoma, T-Cell |
| D020031 | Epstein-Barr Virus Infections |
| D006566 | Herpesviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
| D014412 | Tumor Virus Infections |
| D016393 | Lymphoma, B-Cell |
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| ID | Term |
|---|---|
| D002330 | Carmustine |
| D003520 | Cyclophosphamide |
| D005047 | Etoposide |
| D036102 | Peripheral Blood Stem Cell Transplantation |
| ID | Term |
|---|---|
| D009607 | Nitrosourea Compounds |
| D014508 | Urea |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D009603 | Nitroso Compounds |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D011034 | Podophyllotoxin |
| D013764 | Tetrahydronaphthalenes |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D011083 | Polycyclic Compounds |
| D005960 | Glucosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| 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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