Carmustine, Etoposide, Cyclophosphamide, and Stem Cell Transplant in Treating Patients With HIV-Associated Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00641381
First received: March 21, 2008
Last updated: August 14, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention
Lymphoma
Drug: carmustine
Drug: cyclophosphamide
Drug: etoposide
Other: pharmacological study
Procedure: autologous hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: High Dose Chemotherapy and Combination Anti-HIV Therapy for HIV-Associated Hodgkin's and Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Number of days to engraftment as defined by the standard operating procedures of the department of biostatistics at the City of Hope [ Time Frame: Day 100 post stem cell reinfusion ] [ Designated as safety issue: No ]
  • Feasibility and treatment-associated toxicity of this regimen [ Time Frame: 1 year post stem cell reinfusion ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Ability to mobilize adequate numbers of peripheral blood stem cells (2.5 x 10e6 CD34+cells) [ Time Frame: At the completion of stem cell collection ] [ Designated as safety issue: No ]
  • Disease-free and overall survival [ Time Frame: 2 years post stem cell reinfusion ] [ Designated as safety issue: No ]
  • HIV viral load, CD4+/CD8+ counts, and immune recovery [ Time Frame: 2 years post stem cell reinfusion ] [ Designated as safety issue: No ]

Estimated Enrollment: 25
Study Start Date: March 2000
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (high-dose chemotherapy, anti-HIV therapy)
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.
Drug: carmustine
150 mg/m2 day -7, -6,and -5 prior to stem cell reinfusion
Drug: cyclophosphamide
100 mg/kg on day -2 prior to stem cell reinfusion
Drug: etoposide
60 mg/kg on day -4 prior to stem cell reinfusion
Other: pharmacological study
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
Procedure: autologous hematopoietic stem cell transplantation
Reinfusion of autologous stem cells
Procedure: peripheral blood stem cell transplantation
Reinfusion of autologous stem cells

Detailed Description:

OBJECTIVES:

Primary

  • 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 regimen.
  • 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.

  Eligibility

Ages Eligible for Study:   10 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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:

    • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00641381

Locations
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010-3000
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Amrita Y. Krishnan, MD City of Hope Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT00641381     History of Changes
Other Study ID Numbers: 99067, P30CA033572, CHNMC-99067, CDR0000589621, NCI-2010-00431
Study First Received: March 21, 2008
Last Updated: August 14, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by City of Hope Medical Center:
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

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Carmustine
Etoposide phosphate
Etoposide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 29, 2014