HIV InfectionsPhase 2NCT00001438
A Pilot Study of the Combination of Retinoic Acid and Interferon-Alpha2a for the Treatment of Lymphoproliferative Disorders in Children With Immunodeficiency Syndromes
A Phase 2 study testing all-trans-retinoic acid with IFN-alpha2a in people with HIV Infections and Immunologic Deficiency Syndromes, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Patients with congenital or acquired immunodeficiencies are at an increased risk to develop polyclonal or oligoclonal lymphoid malignancies. Some develop a lymphoproliferative disorder that can follow a clinically aggressive course and may represent a pre-malignant lesion. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- HIV Infections, Immunologic Deficiency Syndromes, Lymphoproliferative Disorders
- What is being tested?
- all-trans-retinoic acid with IFN-alpha2a
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 1995to Dec 2000
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
DISEASE CHARACTERISTICS:
Congenital or acquired immunodeficiency (including HIV-1 infection) with a lymphoproliferative disorder (LPD) of any of the following types:
Severe and/or progressive lymphadenopathy with hypergammaglobulinemia.
Diffuse infiltrative lymphocytosis syndrome.
Clinically symptomatic pulmonary lymphoid hyperplasia/lymphocytic interstitial pneumonitis.
Polyclonal B-cell LPD.
No patients with malignant lymphoma.
No active opportunistic infection requiring acute intervention at entry.
THERAPY:
Biologic Therapy:
At least 30 days since immunomodulating agents or biological response modifiers, e.g.: Interleukin-2, Interferons, Growth hormone, Insulin-like growth factor 1.
Requirement waived for intravenous immunoglobulins for hypogammaglobulinemia.
Concurrent post-transplant immunosuppressants allowed. Doses stable for at least 4 weeks prior to entry.
Chemotherapy: At least 30 days since chemotherapy.
Endocrine Therapy:
Concurrent corticosteroids allowed only for lymphocytic interstitial pneumonitis or an autoimmune process. Doses stable for more than 4 weeks prior to entry.
Radiotherapy: At least 30 days since radiotherapy.
Surgery: Not specified.
Antiretroviral therapy (in patients with HIV infection):
Approved anti-HIV medication required.
Initiated at least 8 weeks prior to entry.
Continued throughout protocol treatment.
Prophylaxis for Pneumocystis carinii pneumonia and/or Mycobacterium avium-intracellulare allowed.
Maintenance antifungal or antiviral therapy allowed.
PATIENT CHARACTERISTICS:
Age: Under 18.
Performance status: Not specified.
One or more of the following laboratory findings (within 4 weeks of starting retinoic acid and interferon-alpha , and which have not resolved within 2 weeks of starting):
Creatinine greater than 2 times the upper limit of normal;
Liver transaminases greater than 5 times the upper limit of normal (children with chronically elevated liver enzymes with a proven etiology can be enrolled, but will not be evaluable for liver toxicity); or
Bilirubin greater than 3 times the upper limit of normal.
Patients receiving treatment for an acute infection must have completed therapy at least 14 days prior to starting therapy with retinoic acid and interferon-alpha.
OTHER:
Able to swallow capsules.
No requirement for drugs suspected of causing pseudotumor cerebri for which alternatives cannot be substituted, e.g.: Tetracycline, Nalidixic acid, Nitrofurantoin, Phenytoin, Lithium, Amiodarone, Vitamin A (except as a multivitamin supplement component).
No critical or clinically unstable illness.
No pregnant or nursing women.
Effective contraception encouraged in fertile patients.
Parent or legal guardian available to give informed consent and deemed sufficiently reliable to return for followup visits.
No critically ill or critically unstable children.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Cancer Institute (NCI)
Bethesda, Maryland, 20892
About this study
Patients with congenital or acquired immunodeficiencies are at an increased risk to develop polyclonal or oligoclonal lymphoid malignancies. Some develop a lymphoproliferative disorder that can follow a clinically aggressive course and may represent a pre-malignant lesion. Although most of these lymphoproliferative disorders are of B-cell origin, T-cell or non-B-non-T-cell processes have also been observed. The pathogenesis is only partially understood.
In the case of pre-malignant conditions it is often difficult to know when and whether a therapeutic intervention is necessary and a careful consideration of potential treatment-associated morbidity is indicated. Therapies have ranged from influencing the possible infectious etiology (by treating with acyclovir), decreasing the amount of immunosuppression (in transplant patients), to the use of immunomodulatory agents, including interferons and interleukins. Recent data have indicated that the use of differentiating agents, such as the retinoids, might offer yet another treatment option. In the current study we will try to get a better understanding of the pathogenesis and natural course of lymphoproliferative disorders in immunodeficient children.
The study will have two parts: an initial observation period to obtain information on the natural course of these disorders, and then a six month treatment period with the combination of a differentiating agent (13-cis-retinoic acid was used until all-trans-retinoic acid became available on 7/96) with an immunomodulatory agent (interferon-alpha2a, IFN-alpha2a).
Read the detailed description
Patients with congenital or acquired immunodeficiencies are at an increased risk to develop polyclonal or oligoclonal lymphoid malignancies. Some develop a lymphoproliferative disorder that can follow a clinically aggressive course and may represent a pre-malignant lesion. Although most of these lymphoproliferative disorders are of B-cell origin, T-cell or non-B-non-T-cell processes have also been observed. The pathogenesis is only partially understood. The Epstein-Barr virus (EBV) is thought to play an important role but the human herpes virus type 6 (HHV-6) has been implicated as well. An imbalance in the expression of several cytokines is observed and it is currently not clear whether this sustains the aberrant proliferation or is a result thereof. In the case of pre-malignant conditions it is often difficult to know when and whether a therapeutic intervention is necessary and a careful consideration of potential treatment-associated morbidity is indicated. Therapies have ranged from influencing the possible infectious etiology (by treating with acyclovir), decreasing the amount of immunosuppression (in transplant patients), to the use of immunomodulatory agents, including interferons and interleukins. Recent data have indicated that the use of differentiating agents, such as the retinoids, might offer yet another treatment option. In the current study we will try to get a better understanding of the pathogenesis and natural course of lymphoproliferative disorders in immunodeficient children. The study will mainly be open to children infected with the human immunodeficiency virus but patients who develop a lymphoproliferative disorder post-transplant or as part of another immunodeficiency state may also be enrolled. The study will have two parts: an initial observation period to obtain information on the natural course of these disorders, and then a six month treatment period with the combination of a differentiating agent (13-cis-retinoic acid was used until all-trans-retinoic acid became available on 7/96) with an immunomodulatory agent (interferon-alpha2a, IFN-alpha2a).
- Being tested
- all-trans-retinoic acid with IFN-alpha2a
- Keywords
- HIV Infection, Immune Response, Pediatric, Pharmacokinetics, Toxicity
- Medical subject headings
- HIV Infections, Immunologic Deficiency Syndromes, Lymphoproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
all-trans-retinoic acid with IFN-alpha2aDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2002 (estimated)
- Study startJun 1995
- Study completionDec 2000
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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 2
- Primary purpose
- Treatment
- Enrolment
- 30 participants
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001438
- Sponsor's protocol ID
- 950144
- Other IDs
- 95-C-0144
- Status last verified
- Jan 2000
- First submitted
- 3 Nov 1999
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Sidell N, Taga T, Hirano T, Kishimoto T, Saxon A. Retinoic acid-induced growth inhibition of a human myeloma cell line via down-regulation of IL-6 receptors. J Immunol. 1991 Jun 1;146(11):3809-14.
PubMed 2033252Su IJ, Cheng AL, Tsai TF, Lay JD. Retinoic acid-induced apoptosis and regression of a refractory Epstein-Barr virus-containing T cell lymphoma expressing multidrug-resistance phenotypes. Br J Haematol. 1993 Dec;85(4):826-8. doi: 10.1111/j.1365-2141.1993.tb03235.x.
PubMed 7918055Aviles A, Diaz-Maqueo JC, Garcia EL, Talavera A, Guzman R. Maintenance therapy with interferon alfa 2b in patients with diffuse large cell lymphoma. Invest New Drugs. 1992 Nov;10(4):351-5. doi: 10.1007/BF00944195.
PubMed 1487412
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of the Combination of Retinoic Acid and Interferon-Alpha2a for the Treatment of Lymphoproliferative Disorders in Children With Immunodeficiency Syndromes
- ClinicalTrials.gov ID
- NCT00001438
- Acronym / sponsor ID
- 950144
- Keywords
- HIV Infection, Immune Response, Pediatric, Pharmacokinetics, Toxicity
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jun 1995
- Study completion
- Dec 2000
- First posted
- 10 Dec 2002 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with congenital or acquired immunodeficiencies are at an increased risk to develop polyclonal or oligoclonal lymphoid malignancies. Some develop a lymphoproliferative disorder that can follow a clinically aggressive course and may represent a pre-malignant lesion. Although most of these lymphoproliferative disorders are of B-cell origin, T-cell or non-B-non-T-cell processes have also been observed. The pathogenesis is only partially understood.
In the case of pre-malignant conditions it is often difficult to know when and whether a therapeutic intervention is necessary and a careful consideration of potential treatment-associated morbidity is indicated. Therapies have ranged from influencing the possible infectious etiology (by treating with acyclovir), decreasing the amount of immunosuppression (in transplant patients), to the use of immunomodulatory agents, including interferons and interleukins. Recent data have indicated that the use of differentiating agents, such as the retinoids, might offer yet another treatment option. In the current study we will try to get a better understanding of the pathogenesis and natural course of lymphoproliferative disorders in immunodeficient children.
The study will have two parts: an initial observation period to obtain information on the natural course of these disorders, and then a six month treatment period with the combination of a differentiating agent (13-cis-retinoic acid was used until all-trans-retinoic acid became available on 7/96) with an immunomodulatory agent (interferon-alpha2a, IFN-alpha2a).
Detailed description
Patients with congenital or acquired immunodeficiencies are at an increased risk to develop polyclonal or oligoclonal lymphoid malignancies. Some develop a lymphoproliferative disorder that can follow a clinically aggressive course and may represent a pre-malignant lesion. Although most of these lymphoproliferative disorders are of B-cell origin, T-cell or non-B-non-T-cell processes have also been observed. The pathogenesis is only partially understood. The Epstein-Barr virus (EBV) is thought to play an important role but the human herpes virus type 6 (HHV-6) has been implicated as well. An imbalance in the expression of several cytokines is observed and it is currently not clear whether this sustains the aberrant proliferation or is a result thereof. In the case of pre-malignant conditions it is often difficult to know when and whether a therapeutic intervention is necessary and a careful consideration of potential treatment-associated morbidity is indicated. Therapies have ranged from influencing the possible infectious etiology (by treating with acyclovir), decreasing the amount of immunosuppression (in transplant patients), to the use of immunomodulatory agents, including interferons and interleukins. Recent data have indicated that the use of differentiating agents, such as the retinoids, might offer yet another treatment option. In the current study we will try to get a better understanding of the pathogenesis and natural course of lymphoproliferative disorders in immunodeficient children. The study will mainly be open to children infected with the human immunodeficiency virus but patients who develop a lymphoproliferative disorder post-transplant or as part of another immunodeficiency state may also be enrolled. The study will have two parts: an initial observation period to obtain information on the natural course of these disorders, and then a six month treatment period with the combination of a differentiating agent (13-cis-retinoic acid was used until all-trans-retinoic acid became available on 7/96) with an immunomodulatory agent (interferon-alpha2a, IFN-alpha2a).
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
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 |
|---|---|---|
| all-trans-retinoic acid with IFN-alpha2a | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 2033252Sidell N, Taga T, Hirano T, Kishimoto T, Saxon A. Retinoic acid-induced growth inhibition of a human myeloma cell line via down-regulation of IL-6 receptors. J Immunol. 1991 Jun 1;146(11):3809-14.
- Background: PubMed 7918055Su IJ, Cheng AL, Tsai TF, Lay JD. Retinoic acid-induced apoptosis and regression of a refractory Epstein-Barr virus-containing T cell lymphoma expressing multidrug-resistance phenotypes. Br J Haematol. 1993 Dec;85(4):826-8. doi: 10.1111/j.1365-2141.1993.tb03235.x.
- Background: PubMed 1487412Aviles A, Diaz-Maqueo JC, Garcia EL, Talavera A, Guzman R. Maintenance therapy with interferon alfa 2b in patients with diffuse large cell lymphoma. Invest New Drugs. 1992 Nov;10(4):351-5. doi: 10.1007/BF00944195.
Related trials for HIV Infections
Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Recruiting
Evaluating the Impact of Using the B-OK Bottles for HIV and ART Literacy in South Africa
HIV, HIV Treatment
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing all-trans-retinoic acid with IFN-alpha2a in people with HIV Infections and Immunologic Deficiency Syndromes, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001438, which also lists 3 linked publications.
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 4 Mar 2008.