LymphomaPhase 4NCT00854581
Zidovudine, Interferon Alfa-2b, PEG-Interferon Alfa-2b in Patients With HTLV-I Associated Adult T-Cell Leukemia/Lymphoma
A Phase 4 study testing PEG-interferon alfa-2b, Interferon alfa-2b and Valproic Acid in people with Lymphoma and Precancerous/Nonmalignant Condition, run by University of Miami at 1 site in United States.
Trial summary
RATIONALE: Human T-cell lymphotropic virus type 1 (HTLV-1) can cause cancer. Zidovudine is an antiviral drug that acts against the human T-cell lymphotropic virus type 1. Giving zidovudine, interferon alfa-2b, and PEG-interferon alfa-2b together may stimulate the immune system and slow down or keep the cancer cell… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma, Precancerous/Nonmalignant Condition
- What is being tested?
- PEG-interferon alfa-2b, Interferon alfa-2b and Valproic Acid
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2007to Nov 2011
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Any stage, histologically or cytological documented adult T-cell leukemia/lymphoma (ATLL), leukemic types only (smoldering, chronic or acute). See Appendix I for definitions of the clinical subtypes.
- Patients who have received prior treatment, including zidovudine and/or IFN, are eligible, provided that zidovudine/IFN therapy did not result in progressive disease.
- Documented HTLV-I infection: documentation may be serologic assay (ELISA, Western blot) and confirmed to be HTLV-I rather than HTLV-2 by differential Western blot (e.g., Genelabs Diagnostics HTLV Blot 2.4) or PCR.
- Measurable or evaluable disease.
- Age 18 or older.
- Karnofsky performance status ≥ 50%.
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- Patients must have adequate end organ and bone marrow function as defined below:
- Absolute neutrophil count ≥ 1,000 cells/mm3 and platelets ≥ 50,000 cells/mm3 unless cytopenias are secondary to ATLL.
- Adequate hepatic function: (transaminase ≤ 7 times the upper limit of normal, total bilirubin < 2.0), unless secondary to hepatic infiltration with lymphoma. If the elevated bilirubin is felt to be secondary to Indinavir or Atazavinir therapy (anti-HIV medications), patients will be allowed to enroll on protocol if the total bilirubin is ≤ 3.5 mg/dl provided that the direct bilirubin is normal.
- Creatinine < 2.0 unless due to lymphomatous infiltration.
- Patients who are HIV+ are also eligible.
- Females with childbearing potential must have a negative serum pregnancy test within 72 hours of entering into the study. Males and females must agree to use adequate birth control if conception is possible during the study. Women must avoid pregnancy and men avoid fathering children while in the study.
- Able to give consent.
- Patients already receiving erythropoietin or granulocyte-colony stimulating factor (G-CSF) are eligible.
Who cannot join
- Concurrent active malignancies, with the exception of in situ carcinoma of the cervix, non-metastatic, non-melanomatous skin cancer, or Kaposi's sarcoma not requiring systemic chemotherapy.
- Grade 3 or 4 cardiac failure and/or ejection fraction < 50%.
- Psychological, familial, sociological or geographical conditions that do not permit treatment and/or medical follow-up required to comply with the study protocol.
- Patients may not be receiving any other investigational agents.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant or breast-feeding women.
- Hypersensitivity to interferon alpha-2b, peginterferon alpha-2b, zidovudine or any component of the formulation
- Autoimmune or viral hepatitis or decompensated liver disease unless due to lymphoma.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Miami Sylvester Comprehensive Cancer Center - Miami
Miami, Florida, 33136
About this study
Official title: Prospective Study of the Molecular Characteristics of Sensitive and Resistant Disease in Patients With HTLV-I Associated Adult T Cell Leukemia Treated With Zidovudine (AZT) Plus Interferon Alpha-2b
RATIONALE: Human T-cell lymphotropic virus type 1 (HTLV-1) can cause cancer. Zidovudine is an antiviral drug that acts against the human T-cell lymphotropic virus type 1. Giving zidovudine, interferon alfa-2b, and PEG-interferon alfa-2b together may stimulate the immune system and slow down or keep the cancer cell from growing.
PURPOSE: This clinical trial is studying how well giving zidovudine together with interferon alfa-2b and PEG-interferon alfa-2b works in treating patients with human T-cell lymphotropic virus type 1-associated adult T-cell leukemia/lymphoma.
Read the detailed description
OUTLINE: This is a multicenter study.
- Induction therapy: Patients receive zidovudine IV twice daily on days 1-14, and recombinant interferon alfa-2b IV twice daily on days 3-14. Patients achieving clinical complete response (CR) proceed to part 1 maintenance therapy; patients achieving partial response (PR) receive another 7 days of zidovudine and recombinant interferon alfa-2b and then proceed to part 1 maintenance therapy.
- Part 1 maintenance therapy: Patients receive oral zidovudine twice daily and PEG-interferon alfa-2b subcutaneously (SC) once weekly, beginning on day 14 or 21 and continue to day 60. Patients are evaluated after completion of part 1 maintenance therapy and proceed to part 2 maintenance therapy.
- Part 2 maintenance therapy: Patients achieving CR with undetectable clonal disease proceed to group A; patients achieving CR with minimal residual disease (by PCR) or PR proceed to group B.
- Group A: Patients receive oral zidovudine twice daily and PEG-interferon alfa-2b SC once weekly. Treatment continues in the absence of disease progression or unacceptable toxicity.
- Group B: Patients receive oral zidovudine twice daily and PEG-interferon alfa-2b SC once weekly for 12 weeks and undergo reevaluation. Patients in continued CR with minimal residual disease or stable PR receive oral valproic acid twice daily, PEG-interferon alfa-2b SC once weekly, and oral zidovudine twice daily for 6 months. At that point (month 9) patients with no detectable clonal disease continue their previous treatment, while patients with minimal residual disease receive PEG-interferon alfa-2b SC and oral zidovudine twice daily in the absence of disease progression or unacceptable toxicity.
Blood samples are collected at baseline, days 1 and 2, and months 3, 6, and 12 for protein, genomic DNA, and RNA analysis. Baseline molecular characteristics of the tumor and tumor response to treatment is assessed.
After completion of study treatment, patients are followed every 3 months for 1 year.
- Conditions
- Lymphoma, Precancerous/Nonmalignant Condition
- Being tested
- PEG-interferon alfa-2b, Interferon alfa-2b, Valproic Acid, Zidovudine
- Keywords
- recurrent adult T-cell leukemia/lymphoma, stage I adult T-cell leukemia/lymphoma, stage II adult T-cell leukemia/lymphoma, stage III adult T-cell leukemia/lymphoma, stage IV adult T-cell leukemia/lymphoma, HTLV-1 infection
- Medical subject headings
- Lymphoma, Precancerous Conditions, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, HTLV-I Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PEG-interferon alfa-2bBiological
Also called PEG-IFN-alfa2b
Administered subcutaneously.
Interferon alfa-2bBiological
Administered intravenously.
Valproic AcidDrug
Also called Depakene
Administered orally.
ZidovudineDrug
Also called Retrovir, AZT
Administered intravenously during Induction Therapy; orally during Maintenance Therapy in all Phases (1, 2A and 2B).
| Study group | Role | What they receive |
|---|---|---|
| Induction (Up to Day 21) | Experimental | For one cycle, up to Day 21. All participants are enrolled to induction therapy phase, then move to the maintenance therapy phase if they achieve complete response (PR) or partial response (PR). Participants who achieve a clinical CR at Day 14 response assessment will go on to Part 1 maintenance therapy. Patients who achieve a PR will receive 7 more days of induction therapy and then go on to Part 1 Maintenance Therapy.:
* Zidovudine:
* Days 1-2: 1.5 grams intravenously (IV) twice daily
* Days 3-21: 1.5 grams IV twice daily
* Interferon alfa-2b (IFN):
* 5 10 million units (mu) intravenously twice daily Receives: Biological: Interferon alfa-2b; Drug: Zidovudine |
| Part 1 Maintenance (Up to Day 60) | Experimental | From Treatment Day 14 or 21 to start of Month 3 (Day 60). Study participants move on to Part 1 Maintenance Therapy only if they achieve complete response (CR) or partial response (PR) after induction therapy. Restaging and molecular evaluation of disease at start of Month 3:
* Zidovudine: 600 mg orally twice daily in all phases of Maintenance Therapy
* PEG-Interferon alfa-2b: 1.5 ug/kg subcutaneously (SQ) once weekly
* Participants then proceed to Part 2 maintenance. Receives: Biological: PEG-interferon alfa-2b; Drug: Zidovudine |
| Part 2A Maintenance (Up to 12 Months) | Experimental | Participants achieving a CR with undetectable clonal disease. Participants will receive therapy for as long as response is maintained:
* Zidovudine: 600 mg orally twice daily
* PEG-Interferon alfa-2b: 1.5 ug/kg subcutaneously (SQ) once weekly Receives: Biological: PEG-interferon alfa-2b; Drug: Zidovudine |
| Part 2B Maintenance (Up to 12 Months) | Experimental | Participants achieving a CR with minimal residual disease (by multiplex PCR) or PR in Part 1:
* Zidovudine: 600 mg or 300 mg orally twice daily, per protocol
* PEG-Interferon alfa-2b: 1.5 ug/kg subcutaneously (SQ) once weekly, per protocol
* Valproic acid, 250 mg orally twice daily, per protocol Receives: Biological: PEG-interferon alfa-2b; Drug: Valproic Acid; Drug: Zidovudine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients Achieving Clinical Response to Protocol Therapy Who Lack IRF-4 and/or c-Rel Expression.
Number of patients achieving clinical response (complete response (CR) + partial response (PR)) who lack interferon regulatory factor 4 (IRF-4) or c-Rel biomarker expression. Treatment response was assessed according to the International Consensus Review's adult T-cell leukemia/lymphoma (ATLL) consensus report by Tsukasaki et al published in the Journal of Clinical Oncology (JCO) in 2009.
For imaging, Cheson criteria was used to assess response:
- Complete response (CR): Disappearance of all clinical, microscopic, and radiographic evidence of disease. All lymph nodes regressed to normal size (≤ 1.5 cm), and previously involved nodes that were 1.1 to 1.5 cm decreased to ≤ 1.0 cm. In addition, abnormally elevated peripheral blood absolute lymphocyte count (ALC) < 4 x 10^9 /L.
- Partial response (PR): ≥ 50% reduction in measurable disease and abnormal lymphocyte count in peripheral blood.
- CR or PR had to persist for a period of at least 4 weeks.
Measured: Up to 12 months post-initiation of protocol therapy
Presence of Minimal Residual Disease at 3 and 6 Months of Maintained Remission and at 1 Year Post Initiation of Therapy
Number of participants achieving complete response (CR) with minimal residual disease at 3, 6 and 12 months post-initiation of protocol therapy. Treatment response was assessed according to the International Consensus Review's adult T-cell leukemia/lymphoma (ATLL) consensus report by Tsukasaki et al published in the Journal of Clinical Oncology (JCO) in 2009.
For imaging, Cheson criteria was used to assess response:
- Complete response (CR): Disappearance of all clinical, microscopic, and radiographic evidence of disease. All lymph nodes regressed to normal size (≤ 1.5 cm), and previously involved nodes that were 1.1 to 1.5 cm decreased to ≤ 1.0 cm. In addition, abnormally elevated peripheral blood absolute lymphocyte count (ALC) < 4 x 10^9 /L.
- Partial response (PR): ≥ 50% reduction in measurable disease and abnormal lymphocyte count in peripheral blood.
- CR or PR had to persist for a period of at least 4 weeks.
Measured: 3, 6 and 12 months.
Expressions of c-Rel, IRF-4 and Other Molecular Events in Participants
Expressions of c-Rel, IRF-4 or other molecular events (p53, p16 mutations) including expansion of novel clones obtained at time of relapse will be compared to baseline data using paired t-test.
Measured: At time of relapse or disease progression, assessed up to 12 months
Number of Participants Exhibiting NF-kB Inhibition Upon Treatment With AZT in Vivo
Number of patients exhibiting NF-kb inhibition upon treatment with AZT in vivo. Investigation of whether AZT functions as an inhibitor of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) in vivo by analyzing serially collected leukemic samples during the first 48 hours of treatment with AZT only. The investigators will report the number of participants exhibiting NF-kB inhibition upon treatment with AZT in vivo and correlate with response using two-sample t-test.
Measured: During 48 hours of first AZT therapy
The Effect of Valproic Acid Therapy on Persistence of Clonal Disease in Patients Who Achieve Clinical Remission
Number of participants achieving a molecular remission after starting valproic acid as evidenced by disappearance of T-cell clonality as measured by gene rearrangement studies using multiplex PCR
Measured: 3, 6 and 12 months.
Secondary outcomes (2)
Failure-free Survival (FFS)
Failure-free survival is the elapsed time from the date of initiation of study treatment 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 was censored at the last documented date of failure-free status.
Measured: From date of treatment initiation until date of documented disease progression, relapse after response, or death from any cause, assessed up to 5 years
Overall Survival
Overall survival (OS) is the elapsed time from the date of initiation of study treatment until date of death from any cause. In the absence of death, the follow-up was censored at date of last contact.
Measured: From date of treatment initiation until date of death, assessed up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2009 (estimated)
- Study startNov 2007
- Primary completionJun 2011
- Study completionNov 2011
Why it stopped: Investigator Decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by University of MiamiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Miami
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Juan C. Ramos, University of Miami
- Investigators
- Juan Carlos Ramos, MD, Principal investigator, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00854581
- Sponsor's protocol ID
- 20070805
- Other IDs
- SCCC-2007055, 5P01CA128115-02
- Status last verified
- Dec 2017
- First submitted
- 28 Feb 2009
- Last updated
- 17 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Study of the Molecular Characteristics of Sensitive and Resistant Disease in Patients With HTLV-I Associated Adult T Cell Leukemia Treated With Zidovudine (AZT) Plus Interferon Alpha-2b
- ClinicalTrials.gov ID
- NCT00854581
- Acronym / sponsor ID
- 20070805
- Conditions
- Lymphoma, Precancerous/Nonmalignant Condition
- Keywords
- recurrent adult T-cell leukemia/lymphoma, stage I adult T-cell leukemia/lymphoma, stage II adult T-cell leukemia/lymphoma, stage III adult T-cell leukemia/lymphoma, stage IV adult T-cell leukemia/lymphoma, HTLV-1 infection
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Investigator Decision
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of MiamiUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Nov 2007
- Primary completion
- Jun 2011 (actual)
- Study completion
- Nov 2011 (actual)
- First posted
- 3 Mar 2009 (estimated)
- Results
- Posted 6 Jan 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Human T-cell lymphotropic virus type 1 (HTLV-1) can cause cancer. Zidovudine is an antiviral drug that acts against the human T-cell lymphotropic virus type 1. Giving zidovudine, interferon alfa-2b, and PEG-interferon alfa-2b together may stimulate the immune system and slow down or keep the cancer cell from growing.
PURPOSE: This clinical trial is studying how well giving zidovudine together with interferon alfa-2b and PEG-interferon alfa-2b works in treating patients with human T-cell lymphotropic virus type 1-associated adult T-cell leukemia/lymphoma.
Detailed description
OUTLINE: This is a multicenter study.
- Induction therapy: Patients receive zidovudine IV twice daily on days 1-14, and recombinant interferon alfa-2b IV twice daily on days 3-14. Patients achieving clinical complete response (CR) proceed to part 1 maintenance therapy; patients achieving partial response (PR) receive another 7 days of zidovudine and recombinant interferon alfa-2b and then proceed to part 1 maintenance therapy.
- Part 1 maintenance therapy: Patients receive oral zidovudine twice daily and PEG-interferon alfa-2b subcutaneously (SC) once weekly, beginning on day 14 or 21 and continue to day 60. Patients are evaluated after completion of part 1 maintenance therapy and proceed to part 2 maintenance therapy.
- Part 2 maintenance therapy: Patients achieving CR with undetectable clonal disease proceed to group A; patients achieving CR with minimal residual disease (by PCR) or PR proceed to group B.
- Group A: Patients receive oral zidovudine twice daily and PEG-interferon alfa-2b SC once weekly. Treatment continues in the absence of disease progression or unacceptable toxicity.
- Group B: Patients receive oral zidovudine twice daily and PEG-interferon alfa-2b SC once weekly for 12 weeks and undergo reevaluation. Patients in continued CR with minimal residual disease or stable PR receive oral valproic acid twice daily, PEG-interferon alfa-2b SC once weekly, and oral zidovudine twice daily for 6 months. At that point (month 9) patients with no detectable clonal disease continue their previous treatment, while patients with minimal residual disease receive PEG-interferon alfa-2b SC and oral zidovudine twice daily in the absence of disease progression or unacceptable toxicity.
Blood samples are collected at baseline, days 1 and 2, and months 3, 6, and 12 for protein, genomic DNA, and RNA analysis. Baseline molecular characteristics of the tumor and tumor response to treatment is assessed.
After completion of study treatment, patients are followed every 3 months for 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Induction (Up to Day 21) | Experimental | Biological: Interferon alfa-2b, Drug: ZidovudineFor one cycle, up to Day 21. All participants are enrolled to induction therapy phase, then move to the maintenance therapy phase if they achieve complete response (PR) or partial response (PR). Participants who achieve a clinical CR at Day 14 response assessment will go on to Part 1 maintenance therapy. Patients who achieve a PR will receive 7 more days of induction therapy and then go on to Part 1 Maintenance Therapy.: * Zidovudine: * Days 1-2: 1.5 grams intravenously (IV) twice daily * Days 3-21: 1.5 grams IV twice daily * Interferon alfa-2b (IFN): * 5 10 million units (mu) intravenously twice daily |
| Part 1 Maintenance (Up to Day 60) | Experimental | Biological: PEG-interferon alfa-2b, Drug: ZidovudineFrom Treatment Day 14 or 21 to start of Month 3 (Day 60). Study participants move on to Part 1 Maintenance Therapy only if they achieve complete response (CR) or partial response (PR) after induction therapy. Restaging and molecular evaluation of disease at start of Month 3: * Zidovudine: 600 mg orally twice daily in all phases of Maintenance Therapy * PEG-Interferon alfa-2b: 1.5 ug/kg subcutaneously (SQ) once weekly * Participants then proceed to Part 2 maintenance. |
| Part 2A Maintenance (Up to 12 Months) | Experimental | Biological: PEG-interferon alfa-2b, Drug: ZidovudineParticipants achieving a CR with undetectable clonal disease. Participants will receive therapy for as long as response is maintained: * Zidovudine: 600 mg orally twice daily * PEG-Interferon alfa-2b: 1.5 ug/kg subcutaneously (SQ) once weekly |
| Part 2B Maintenance (Up to 12 Months) | Experimental | Biological: PEG-interferon alfa-2b, Drug: Valproic Acid, Drug: ZidovudineParticipants achieving a CR with minimal residual disease (by multiplex PCR) or PR in Part 1: * Zidovudine: 600 mg or 300 mg orally twice daily, per protocol * PEG-Interferon alfa-2b: 1.5 ug/kg subcutaneously (SQ) once weekly, per protocol * Valproic acid, 250 mg orally twice daily, per protocol |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Any stage, histologically or cytological documented adult T-cell leukemia/lymphoma (ATLL), leukemic types only (smoldering, chronic or acute). See Appendix I for definitions of the clinical subtypes.
- Patients who have received prior treatment, including zidovudine and/or IFN, are eligible, provided that zidovudine/IFN therapy did not result in progressive disease.
- Documented HTLV-I infection: documentation may be serologic assay (ELISA, Western blot) and confirmed to be HTLV-I rather than HTLV-2 by differential Western blot (e.g., Genelabs Diagnostics HTLV Blot 2.4) or PCR.
- Measurable or evaluable disease.
- Age 18 or older.
Key exclusion criteria (8 listed)
- Concurrent active malignancies, with the exception of in situ carcinoma of the cervix, non-metastatic, non-melanomatous skin cancer, or Kaposi's sarcoma not requiring systemic chemotherapy.
- Grade 3 or 4 cardiac failure and/or ejection fraction < 50%.
- Psychological, familial, sociological or geographical conditions that do not permit treatment and/or medical follow-up required to comply with the study protocol.
- Patients may not be receiving any other investigational agents.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PEG-interferon alfa-2bAlso: PEG-IFN-alfa2bAdministered subcutaneously. | Biological | Part 1 Maintenance (Up to Day 60), Part 2A Maintenance (Up to 12 Months), Part 2B Maintenance (Up to 12 Months) |
| Interferon alfa-2bAdministered intravenously. | Biological | Induction (Up to Day 21) |
| Valproic AcidAlso: DepakeneAdministered orally. | Drug | Part 2B Maintenance (Up to 12 Months) |
| ZidovudineAlso: Retrovir, AZTAdministered intravenously during Induction Therapy; orally during Maintenance Therapy in all Phases (1, 2A and 2B). | Drug | Induction (Up to Day 21), Part 1 Maintenance (Up to Day 60), Part 2A Maintenance (Up to 12 Months), Part 2B Maintenance (Up to 12 Months) |
Primary outcome
Number of Patients Achieving Clinical Response to Protocol Therapy Who Lack IRF-4 and/or c-Rel Expression.
Time frame: Up to 12 months post-initiation of protocol therapy
Number of patients achieving clinical response (complete response (CR) + partial response (PR)) who lack interferon regulatory factor 4 (IRF-4) or c-Rel biomarker expression. Treatment response was assessed according to the International Consensus Review's adult T-cell leukemia/lymphoma (ATLL) consensus report by Tsukasaki et al published in the Journal of Clinical Oncology (JCO) in 2009. For imaging, Cheson criteria was used to assess response: * Complete response (CR): Disappearance of all clinical, microscopic, and radiographic evidence of disease. All lymph nodes regressed to normal size (≤ 1.5 cm), and previously involved nodes that were 1.1 to 1.5 cm decreased to ≤ 1.0 cm. In addition, abnormally elevated peripheral blood absolute lymphocyte count (ALC) < 4 x 10^9 /L. * Partial response (PR): ≥ 50% reduction in measurable disease and abnormal lymphocyte count in peripheral blood. * CR or PR had to persist for a period of at least 4 weeks.
Presence of Minimal Residual Disease at 3 and 6 Months of Maintained Remission and at 1 Year Post Initiation of Therapy
Time frame: 3, 6 and 12 months.
Number of participants achieving complete response (CR) with minimal residual disease at 3, 6 and 12 months post-initiation of protocol therapy. Treatment response was assessed according to the International Consensus Review's adult T-cell leukemia/lymphoma (ATLL) consensus report by Tsukasaki et al published in the Journal of Clinical Oncology (JCO) in 2009. For imaging, Cheson criteria was used to assess response: * Complete response (CR): Disappearance of all clinical, microscopic, and radiographic evidence of disease. All lymph nodes regressed to normal size (≤ 1.5 cm), and previously involved nodes that were 1.1 to 1.5 cm decreased to ≤ 1.0 cm. In addition, abnormally elevated peripheral blood absolute lymphocyte count (ALC) < 4 x 10^9 /L. * Partial response (PR): ≥ 50% reduction in measurable disease and abnormal lymphocyte count in peripheral blood. * CR or PR had to persist for a period of at least 4 weeks.
Expressions of c-Rel, IRF-4 and Other Molecular Events in Participants
Time frame: At time of relapse or disease progression, assessed up to 12 months
Expressions of c-Rel, IRF-4 or other molecular events (p53, p16 mutations) including expansion of novel clones obtained at time of relapse will be compared to baseline data using paired t-test.
Number of Participants Exhibiting NF-kB Inhibition Upon Treatment With AZT in Vivo
Time frame: During 48 hours of first AZT therapy
Number of patients exhibiting NF-kb inhibition upon treatment with AZT in vivo. Investigation of whether AZT functions as an inhibitor of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) in vivo by analyzing serially collected leukemic samples during the first 48 hours of treatment with AZT only. The investigators will report the number of participants exhibiting NF-kB inhibition upon treatment with AZT in vivo and correlate with response using two-sample t-test.
The Effect of Valproic Acid Therapy on Persistence of Clonal Disease in Patients Who Achieve Clinical Remission
Time frame: 3, 6 and 12 months.
Number of participants achieving a molecular remission after starting valproic acid as evidenced by disappearance of T-cell clonality as measured by gene rearrangement studies using multiplex PCR
2 secondary outcomes
Failure-free Survival (FFS)
Time frame: From date of treatment initiation until date of documented disease progression, relapse after response, or death from any cause, assessed up to 5 years
Overall Survival
Time frame: From date of treatment initiation until date of death, assessed up to 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Juan Carlos Ramos, MD principal investigator
University of Miami
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing PEG-interferon alfa-2b, Interferon alfa-2b and Valproic Acid in people with Lymphoma and Precancerous/Nonmalignant Condition, run by University of Miami at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Jan 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients Achieving Clinical Response to Protocol Therapy Who Lack IRF-4 and/or c-Rel Expression. (time frame: Up to 12 months post-initiation of protocol therapy). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2018.