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High Dose Chemotherapy and Combination Anti-HIV Therapy for HIV-Associated Hodgkin's and Non-Hodgkin's Lymphoma

10 Years
60 Years
Open (Enrolling)

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Trial Information

High Dose Chemotherapy and Combination Anti-HIV Therapy for HIV-Associated Hodgkin's and Non-Hodgkin's Lymphoma



- To evaluate the feasibility and toxicity of high-dose chemotherapy comprising
carmustine, etoposide, and cyclophosphamide followed by autologous stem cell infusion
in patients with HIV-associated lymphoma receiving combination anti-HIV therapy and to
determine the efficiency of stem cell collection from these patients.

- To estimate the disease-free and overall survival of patients treated with this

- To evaluate HIV viral load, CD+4/CD+8 counts, and immune recovery after high-dose anti-
lymphoma chemotherapy.

- To determine the pharmacokinetics of high-dose etoposide in patients receiving highly
active anti-retroviral therapy (HAART).

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.

- 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.

- Autologous PBSC transplantation: Patients receive PBSC infusion on day 0. Patients
undergo blood sample collection periodically for pharmacokinetic studies of etoposide.

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.

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

- 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

- A minimum of 2.5 x 10^6 CD34 cells/kg must have been collected

- Hodgkin's Lymphoma:

- Partial response after standard chemotherapy OR

- First relapse after initial complete remission with standard chemotherapy

- Non-Hodgkin's Lymphoma:

- First complete remission after standard chemotherapy with high risk features as
specified by the International Prognostic Index;

- Partial response after standard chemotherapy; OR

- Relapse after initial complete remission with standard chemotherapy

Exclusion Criteria:

- Active bacterial or fungal infection

- AIDS related opportunistic infection within past year, excluding treatment-responsive
Mycobacterium Avium Intracellular infection, and treatment-responsive oral thrush,
herpes simplex or herpes zoster

- Active cytomegalovirus (CMV) retinitis or other CMV-related organ dysfunction;
patients with a history of treated CMV infection are not excluded

- Relapse of pneumocystis carinii pneumonia within the past year

- AIDS related syndromes or symptoms that pose a perceived excessive risk for
transplantation-related morbidity as determined by the principle investigator

- Intractable and severe diarrhea as defined as > 1500 cc diarrheal fluid per day of
diarrhea causing persistent severed electrolyte abnormalities or hypoalbuminemia

- History of grade III hemorrhagic cystitis due to prior chemotherapy

- Pregnant or nursing women

- Any prior malignancy except treated basal cell carcinoma of the skin; females with
cervical dysplasia may be included at the discretion of the treating physician and
the principle investigator

- Patients with a history of positive cerebrospinal fluid (CSF) cytology that has
become negative with intrathecal chemotherapy are eligible; patients should have a
negative spinal fluid cytology within thirty days prior to enrollment

- Abnormal cytogenetics on screening bone marrow biopsy

- Psychosocial conditions that hinder compliance

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of days to engraftment as defined by the standard operating procedures of the department of biostatistics at the City of Hope

Outcome Time Frame:

Day 100 post stem cell reinfusion

Safety Issue:


Principal Investigator

Amrita Y. Krishnan, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

City of Hope Medical Center


United States: Institutional Review Board

Study ID:




Start Date:

March 2000

Completion Date:

Related Keywords:

  • Lymphoma
  • stage III adult Hodgkin lymphoma
  • stage III childhood Hodgkin lymphoma
  • stage IV adult Hodgkin lymphoma
  • stage IV childhood Hodgkin lymphoma
  • recurrent childhood lymphoblastic lymphoma
  • recurrent mantle cell lymphoma
  • recurrent adult Hodgkin lymphoma
  • recurrent/refractory childhood Hodgkin lymphoma
  • recurrent adult T-cell leukemia/lymphoma
  • recurrent cutaneous T-cell non-Hodgkin lymphoma
  • AIDS-related diffuse large cell lymphoma
  • AIDS-related diffuse mixed cell lymphoma
  • AIDS-related immunoblastic large cell lymphoma
  • AIDS-related lymphoblastic lymphoma
  • AIDS-related small noncleaved cell lymphoma
  • Burkitt lymphoma
  • stage III adult diffuse large cell lymphoma
  • stage III adult diffuse mixed cell lymphoma
  • stage IV adult diffuse large cell lymphoma
  • stage IV adult diffuse mixed cell lymphoma
  • stage III grade 3 follicular lymphoma
  • stage IV grade 3 follicular lymphoma
  • stage III adult immunoblastic large cell lymphoma
  • stage IV adult immunoblastic large cell lymphoma
  • stage III adult lymphoblastic lymphoma
  • stage III childhood lymphoblastic lymphoma
  • stage IV adult lymphoblastic lymphoma
  • stage IV childhood lymphoblastic lymphoma
  • stage III adult Burkitt lymphoma
  • stage IV adult Burkitt lymphoma
  • HIV Infections
  • Treatment Experienced
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Large-Cell, Immunoblastic
  • Lymphoma, AIDS-Related



City of Hope Medical Center Duarte, California  91010