Phase II of Chemotherapy for Relapsed Epstein Barr Virus Associated Lymphoma
Epstein Barr Virus Associated Non Hodgkin's Lymphoma
Epstein Barr Virus Associated Hodgkin's Lymphoma
Post-Transplant Lymphoproliferative Disease
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Chemotherapy (Doxorubicin, Methotrexate and Leucovorin) in Combination With Antiviral-Based Therapy (Zidovudine + Hydroxyurea) for AIDS, Immunocompromised, or Immunocompetent Patients With Relapsed or CNS Positive Epstein Barr Virus Associated Lymphoma|
- Rate of Complete Response to Protocol Therapy [ Time Frame: Through Duration of Protocol Therapy, Up to six 21-day cycles (+/- 7 days) ] [ Designated as safety issue: No ]
Complete Response (CR) rate in study participants to protocol therapy. Response will be assessed via CT Scan and bone marrow aspirate/biopsy, if applicable. Complete response criteria include:
- Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities definitely assignable to NHL;
- All lymph nodes and tumor masses disappeared or regressed to normal size (≤ 1.5 cm in their greatest transverse diameters for nodes > 1.5 cm before therapy);
- Previously involved nodes that were 1.1 to 1.5 cm in their greatest transverse diameter (GTD) before treatment must have decreased to ≤ 1 cm in their GTD after treatment, or by more than 75% bin the sum of the products of the greatest diameters (SPD);
- No new sites of disease.
- Rate of Overall Survival [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]Rate of overall survival of study participants. Overall survival (OS) will be measured from the date of initiation of study treatment until date of death from any cause. In the absence of death, the follow-up will be censored at date of last contact (censored observation).
- Rate of Failure-Free Survival (FFS) [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]Rate of failure-free survival of study participants. Failure-free survival (FFS) will be measured from the date of treatment initiation until date of documented disease progression, relapse after response, or death from any cause. For patients alive and free of relapse or progression, follow-up time will be censored at the last documented date of failure-free status.
- Rate of Toxicity Related to Protocol Therapy [ Time Frame: Through Duration of Protocol Therapy, Up to six 21-day cycles (+/- 7 days) ] [ Designated as safety issue: Yes ]Rate of adverse events, serious adverse events or other toxicities related to protocol therapy in study participants.
- HIV Viral Load in Positive Subjects Before, During and After Protocol Therapy [ Time Frame: From Baseline Up to 1 Year Post-Therapy ] [ Designated as safety issue: No ]Measurement of HIV Viral Load in positive subjects before, during and after protocol therapy to assess the effect of protocol therapy on immune reconstitution or exhaustion.
- T-Cell Subset Levels in Peripheral Blood Before, During and After Protocol Therapy [ Time Frame: From Baseline Up to 1 Year Post-Therapy ] [ Designated as safety issue: No ]Measurement of T-cell subset levels in peripheral blood before, during and after protocol therapy to assess the effect of protocol therapy on immune re-constitution or exhaustion.
- EBV Viral Load in Peripheral Blood Before, During and after Protocol Therapy [ Time Frame: From Baseline Up to 1 year Post-Therapy ] [ Designated as safety issue: No ]Measurement of EBV viral load in peripheral blood in study participants before, after treatment, and during surveillance in order to correlate the presence of with tumor load and disease status.
- EBV Reactivation in Circulating Peripheral Blood Memory B-cells Before and After Protocol Therapy. [ Time Frame: From Baseline Up to 1 year Post-Therapy ] [ Designated as safety issue: No ]Measurement of EBV reactivation in circulating peripheral blood memory B-cells before and after treatment with chemotherapy/ZDV in order to assess the drug effect on EBV latency.
- Baseline Tumor EBV Gene Expression Profile in Study Participants [ Time Frame: Baseline ] [ Designated as safety issue: No ]Determine baseline tumor EBV gene expression profile to assess viral thymidine kinases. (BXLF1/vTK and BGLF4/PK), EBV latency pattern (I, II or III) and lytic phase.
- Measurement of Immune Activation Markers and Inflammation in Peripheral Blood [ Time Frame: Through Duration of Response to Protocol Therapy Until Disease Progression, Up to 5 years ] [ Designated as safety issue: No ]Measurement of immune activation markers and inflammation in peripheral blood in response to treatment and EBV reactivation.
|Study Start Date:||April 2011|
|Estimated Primary Completion Date:||April 2019 (Final data collection date for primary outcome measure)|
Experimental: Chemotherapy + Antiviral-Based Therapy
Combination Chemotherapy for up to six (6) 21-day cycles and Antiviral-Based Therapy:
Doxorubicin 20 mg/m2 intravenously will be administered on Day 1 in patients with systemic (non-primary CNS) lymphoma as per institutional guidelines
Other Name: AdriamycinDrug: Methotrexate
Methotrexate administered starting on Day 2, per study protocol.
Other Names:Drug: Leucovorin
Leucovorin administered first intravenously 24 hours after start of Methotrexate infusion, then orally every 6 hours for at least 10 doses, per study protocol.
Other Names:Biological: Hydroxyurea
Hydroxyurea administered orally twice daily starting on Day 2, and continuing for a total of 10 doses, per study protocol
Other Names:Drug: Zidovudine
Zidovudine administered first intravenously on Day 2, and then orally twice daily for 10 doses, per study protocol.
Other Names:Drug: Rituximab
Rituximab is optional and will be administered to study participants, per study protocol.
Other Name: Rituxan
Please refer to this study by its ClinicalTrials.gov identifier: NCT01964755
|United States, Florida|
|University of Miami||Recruiting|
|Miami, Florida, United States, 33136|
|Contact: Juan Carlos Ramos, MD 305-243-6611 email@example.com|
|Principal Investigator: Juan Carlos Ramos, MD|
|United States, North Carolina|
|University of North Carolina at Chapel Hill||Recruiting|
|Chapel Hill, North Carolina, United States, 27999|
|Contact: Dirk Dittmer, PhD 919-966-7960 firstname.lastname@example.org|
|Principal Investigator: Dirk Dittmer, PhD|
|Study Chair:||Juan Carlos Ramos, MD||University of Miami|