Acute Lymphoblastic LeukemiaPhase 2IL2 for GVHDNCT00539695
Low Dose IL-2, Hematopoietic Stem Cell Transplantation, IL2 for GVHD
A Phase 2 study testing IL-2 in people with Acute Lymphoblastic Leukemia and ALL, run by Baylor College of Medicine at 2 sites in United States.
Trial summary
Patients are being asked to participate in this study because treatment for their disease requires a stem cell transplant (SCT). Stem cells are the source of normal blood cells found in the bone marrow and lead to recovery of blood counts after bone marrow transplantation. Read more about this study
- Who is it for?
- Ages Up to 70 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia, ALL, Acute Myelogenous Leukemia
- What is being tested?
- IL-2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 2 sitesUnited States
- Study dates
- Jun 2007to Mar 2014
- Phase
- Phase 2
- 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 Up to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients will be eligible for initial enrollment on this study as long as they meet the following criteria:
- Diagnosis of acute lymphoblastic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, myelodysplastic syndrome, myeloproliferative disorder, Hodgkin lymphoma, non-Hodgkin lymphoma or non-malignant disease requiring allogeneic HSCT
- Birth to age 70 years of age
- Study entry consent is signed and faxed to Research Coordinator
- At least day +7 post transplant
- Less than or equal to 30 days post transplant
Show all 11Show fewer
- Lansky or Karnofsky score greater than or equal to 50%
- Total bilirubin less than or equal to 1.5mg/dL
- Alanine aminotransferase level (ALT) less than or equal to five times normal, serum direct bilirubin less than or equal to 1.5mg/dL, albumin greater than or equal to 3.0gm/dL
- Serum creatinine less than three times normal or creatinine clearance greater than 80mg/min/1.73m2
- Ensure that informed consent signed and faxed to Research Coordinator
Who cannot join
- Patients will be ineligible to receive IL-2 injections if any of the following is true:
- Active, acute GVHD greater than or equal to grade II
- Serious, active bacterial, fungal or viral infection (i.e. intensive care)
- Clinical Signs of severe pulmonary dysfunction
- Clinical Signs of sever cardiac dysfunction
- Receiving corticosteroids as GVHD treatment
- Hypersensitivity or allergy to IL-2
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Texas Children's Hospital
Houston, Texas, 77030
The Methodist Hospital
Houston, Texas, 77030
About this study
Official title: Phase II Trial Using Low Dose IL-2 to Induce Regulatory T Cells in Patients After Allogeneic Hematopoietic Stem Cell Transplantation as Graft Versus Host Disease Prophylaxis
Patients are being asked to participate in this study because treatment for their disease requires a stem cell transplant (SCT). Stem cells are the source of normal blood cells found in the bone marrow and lead to recovery of blood counts after bone marrow transplantation. With stem cell transplants, regardless of whether the donor is a full match to the patient or not, there is a risk of developing graft-versus-host disease (GVHD).
GVHD is a serious and sometimes fatal side effect of SCT. GVHD occurs when the new donor stem cells (graft) recognizes that the body tissues of the patient (host) are different from those of the donor. When this happens, cells in the graft may attack the host organs. How much this happens and how severe the GVHD is depends on many things, including how different the donors cells are, the strength of the drugs given in preparation for the transplant, the quality of transplanted cells and the age of the person receiving the transplant.
Read more
Typically, acute GVHD occurs in the first 100 days following transplant, while chronic GVHD occurs after day 100. Acute GVHD most often involves the skin, where it can cause anywhere from a mild rash to complete removal of skin; liver, where it can anywhere from a rise in liver function tests to liver failure; and the gut, where it can cause anywhere from mild diarrhea to profuse, life-threatening diarrhea. Most patients who develop GVHD experience a mild to moderate form, but some patients develop the severe, life-threatening form.
Previous studies have shown that patients who receive SCT's can have a lower number of special T cells in their blood, called regulatory T cells, than people who have not received stem cell transplants. When regulatory T cells are low, there appears to be an increased rate of severe, acute GVHD. A drug known as IL-2 (Proleukin) has been shown to increase the number of regulatory T cells in patients following stem cell transplant, and in this study investigators plan to give low dose IL-2 after transplant.
This study is called a phase II study because its major purpose is to find out whether using a low-dose of IL-2 will be effective in preventing acute GVHD. Other important purposes are to find out if this treatment helps the patient's immune system recover regulatory T cells faster after the transplant. This study will assess the safety and toxicity of low-dose IL-2 given to patients after transplantation and determine whether this drug is helpful in preventing GVHD.
Read the detailed description
Participation in this protocol will last about 1 year.
To participate in this study, the patient will need to have undergone a stem cell transplant. Before the treatment starts, investigators would like to test the patient's blood blood for the number of regulatory T cells already present before beginning IL-2.
Treatment Plan:
Before the conditioning treatment for the transplant, 30 to 40 ml (6 to 8 teaspoonfuls) of blood will be collected from the patient for regulatory T cell analysis. Approximately same amount of blood will also be collected on day 0 (the day of the transplant), and at the following times after the transplant: day 7 (the day the IL-2 will most likely start) then weekly for another eleven weeks, then monthly for 8 months.
On approximately day 7 following the transplant, if the patient is well and meets the eligibility requirements, the IL-2 injections will begin. These will be given subcutaneously (as a small injection just under the skin) three times per week for 6 weeks. The injections may also been given through a special catheter, called an Insuflon catheter, that is placed just under the skin for a week at a time. The first dose must be given in the hospital, but the remaining doses can be given at home. The patient will be taught how to give the injections to him/ herself.
If the patient's body has no serious toxicities from the IL-2 and has not developed severe GVHD, the patient can continue to get the injections the same way for an additional 6 weeks. If at any time the patient develops severe GVHD or serious toxicity related to the IL-2,the injections will be stopped. If the patient's disease returns (relapse) or he or she does not engraft (accept the donor graft), the patient will be removed from the study.
The patient's labs will be followed closely while he/she is receiving the IL-2 injections, as well as heart, kidney and lung functions; however, these are all standard tests that the patient will receive after transplant regardless of participation in this study.
- Conditions
- Acute Lymphoblastic Leukemia, ALL, Acute Myelogenous Leukemia, AML, Chronic Myelogenous Leukemia, Myelodysplastic Syndrome
- Being tested
- IL-2
- Keywords
- Stem Cell transplant, Graft verus host disease, IL-2, acute lymphoblastic leukemia, ALL, acute myelogenous leukemia, AML, chronic myelogenous leukemia, myelodysplastic syndrome, myeloproliferative disorder, Hodgkin lymphoma, non-Hodgkin lymphoma, non-malignant diseases requiring allogeneic HSCT
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Myelodysplastic Syndromes, Myeloproliferative Disorders, Hodgkin Disease, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IL-2Biological
Also called Proleukin, Aldesleukin, Interleukin-2
IL2 Administration:
Patients will be given a fixed dose (1x10e5 units/m2/dose) of IL-2 given as a subcutaneous injection three times weekly (separated by at least one day) for 6 weeks beginning no earlier than day +7 after HSCT but beginning no later than 30 days after HSCT. If the patient has not developed >grade I side effects to IL-2 and has not developed >grade I GVHD then the patient may continue the IL-2 for 6 additional weeks. Time will be measured as 'week beginning with first IL-2 injection.
| Study group | Role | What they receive |
|---|---|---|
| IL2 Administration | Experimental | SCHEDULE OF IL-2 ADMINISTRATION: Patients will receive a fixed dose (1x10e5 units/m2/dose) of IL-2 given as a subcutaneous injection three times weekly (separated by at least one day) for 6 weeks beginning no earlier than day +7 after HSCT but beginning no later than 30 days after HSCT.
Time will be measured as 'week beginning with first IL-2 injection.'
T cell Induction via IL-2 to reduce GVHD Receives: Biological: IL-2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Dose Limiting Toxicities
Assessment of the safety and the toxicity of low-dose IL-2, administered according to the dosage described in this protocol, in this group of patients The outcome measure is the proportion of participants with dose limiting toxicities.
Measured: 6-12 weeks
Secondary outcomes (2)
Rate of Severe (Grade III or IV) Acute GVHD
To determine the efficacy of low-dose IL-2 in the prevention of severe (grade III or IV) acute GVHD
Measured: Up to 12 weeks on low-dose IL-2
Percentage Change in CD4+ CD25+ FoxP3+ Regulatory T Cells (Tregs) From Pre to Post IL-2 Infusions
To investigate the immunomodulatory effects of IL-2 administered after allogeneic hematopoietic stem cell transplantation
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2007 (estimated)
- Study startJun 2007
- Primary completionApr 2013
- Study completionMar 2014
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe 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
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine
- Responsible party
- Principal investigator, Rayne Rouce, Baylor College of Medicine
- Investigators
- Rayne Rouce, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00539695
- Sponsor's protocol ID
- H-20971-IL2 for GvHD
- Other IDs
- IL-2 for GVHD
- Acronym
- IL2 for GVHD
- Status last verified
- Apr 2018
- First submitted
- 2 Oct 2007
- Last updated
- 4 May 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Kennedy-Nasser AA, Ku S, Castillo-Caro P, Hazrat Y, Wu MF, Liu H, Melenhorst J, Barrett AJ, Ito S, Foster A, Savoldo B, Yvon E, Carrum G, Ramos CA, Krance RA, Leung K, Heslop HE, Brenner MK, Bollard CM. Ultra low-dose IL-2 for GVHD prophylaxis after allogeneic hematopoietic stem cell transplantation mediates expansion of regulatory T cells without diminishing antiviral and antileukemic activity. Clin Cancer Res. 2014 Apr 15;20(8):2215-25. doi: 10.1158/1078-0432.CCR-13-3205. Epub 2014 Feb 26.
PubMed 24573552
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial Using Low Dose IL-2 to Induce Regulatory T Cells in Patients After Allogeneic Hematopoietic Stem Cell Transplantation as Graft Versus Host Disease Prophylaxis
- ClinicalTrials.gov ID
- NCT00539695
- Acronym / sponsor ID
- IL2 for GVHD / H-20971-IL2 for GvHD
- Conditions
- Acute Lymphoblastic Leukemia, ALL, Acute Myelogenous Leukemia, AML, Chronic Myelogenous Leukemia, Myelodysplastic Syndrome
- Keywords
- Stem Cell transplant, Graft verus host disease, IL-2, acute lymphoblastic leukemia, ALL, acute myelogenous leukemia, AML, chronic myelogenous leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Collaborators
- The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine
- Study start
- Jun 2007
- Primary completion
- Apr 2013 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 4 Oct 2007 (estimated)
- Results
- Posted 4 Jul 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients are being asked to participate in this study because treatment for their disease requires a stem cell transplant (SCT). Stem cells are the source of normal blood cells found in the bone marrow and lead to recovery of blood counts after bone marrow transplantation. With stem cell transplants, regardless of whether the donor is a full match to the patient or not, there is a risk of developing graft-versus-host disease (GVHD).
GVHD is a serious and sometimes fatal side effect of SCT. GVHD occurs when the new donor stem cells (graft) recognizes that the body tissues of the patient (host) are different from those of the donor. When this happens, cells in the graft may attack the host organs. How much this happens and how severe the GVHD is depends on many things, including how different the donors cells are, the strength of the drugs given in preparation for the transplant, the quality of transplanted cells and the age of the person receiving the transplant.
Typically, acute GVHD occurs in the first 100 days following transplant, while chronic GVHD occurs after day 100. Acute GVHD most often involves the skin, where it can cause anywhere from a mild rash to complete removal of skin; liver, where it can anywhere from a rise in liver function tests to liver failure; and the gut, where it can cause anywhere from mild diarrhea to profuse, life-threatening diarrhea. Most patients who develop GVHD experience a mild to moderate form, but some patients develop the severe, life-threatening form.
Previous studies have shown that patients who receive SCT's can have a lower number of special T cells in their blood, called regulatory T cells, than people who have not received stem cell transplants. When regulatory T cells are low, there appears to be an increased rate of severe, acute GVHD. A drug known as IL-2 (Proleukin) has been shown to increase the number of regulatory T cells in patients following stem cell transplant, and in this study investigators plan to give low dose IL-2 after transplant.
This study is called a phase II study because its major purpose is to find out whether using a low-dose of IL-2 will be effective in preventing acute GVHD. Other important purposes are to find out if this treatment helps the patient's immune system recover regulatory T cells faster after the transplant. This study will assess the safety and toxicity of low-dose IL-2 given to patients after transplantation and determine whether this drug is helpful in preventing GVHD.
Detailed description
Participation in this protocol will last about 1 year.
To participate in this study, the patient will need to have undergone a stem cell transplant. Before the treatment starts, investigators would like to test the patient's blood blood for the number of regulatory T cells already present before beginning IL-2.
Treatment Plan:
Before the conditioning treatment for the transplant, 30 to 40 ml (6 to 8 teaspoonfuls) of blood will be collected from the patient for regulatory T cell analysis. Approximately same amount of blood will also be collected on day 0 (the day of the transplant), and at the following times after the transplant: day 7 (the day the IL-2 will most likely start) then weekly for another eleven weeks, then monthly for 8 months.
On approximately day 7 following the transplant, if the patient is well and meets the eligibility requirements, the IL-2 injections will begin. These will be given subcutaneously (as a small injection just under the skin) three times per week for 6 weeks. The injections may also been given through a special catheter, called an Insuflon catheter, that is placed just under the skin for a week at a time. The first dose must be given in the hospital, but the remaining doses can be given at home. The patient will be taught how to give the injections to him/ herself.
If the patient's body has no serious toxicities from the IL-2 and has not developed severe GVHD, the patient can continue to get the injections the same way for an additional 6 weeks. If at any time the patient develops severe GVHD or serious toxicity related to the IL-2,the injections will be stopped. If the patient's disease returns (relapse) or he or she does not engraft (accept the donor graft), the patient will be removed from the study.
The patient's labs will be followed closely while he/she is receiving the IL-2 injections, as well as heart, kidney and lung functions; however, these are all standard tests that the patient will receive after transplant regardless of participation in this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IL2 Administration | Experimental | Biological: IL-2SCHEDULE OF IL-2 ADMINISTRATION: Patients will receive a fixed dose (1x10e5 units/m2/dose) of IL-2 given as a subcutaneous injection three times weekly (separated by at least one day) for 6 weeks beginning no earlier than day +7 after HSCT but beginning no later than 30 days after HSCT. Time will be measured as 'week beginning with first IL-2 injection.' T cell Induction via IL-2 to reduce GVHD |
Who may qualify
- Ages
- Up to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- Patients will be eligible for initial enrollment on this study as long as they meet the following criteria:
- Diagnosis of acute lymphoblastic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, myelodysplastic syndrome, myeloproliferative disorder, Hodgkin lymphoma, non-Hodgkin lymphoma or non-malignant disease requiring allogeneic HSCT
- Birth to age 70 years of age
- Study entry consent is signed and faxed to Research Coordinator
- At least day +7 post transplant
Key exclusion criteria (7 listed)
- Active, acute GVHD greater than or equal to grade II
- Serious, active bacterial, fungal or viral infection (i.e. intensive care)
- Clinical Signs of severe pulmonary dysfunction
- Clinical Signs of sever cardiac dysfunction
- Receiving corticosteroids as GVHD treatment
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 |
|---|---|---|
| IL-2Also: Proleukin, Aldesleukin, Interleukin-2IL2 Administration: Patients will be given a fixed dose (1x10e5 units/m2/dose) of IL-2 given as a subcutaneous injection three times weekly (separated by at least one day) for 6 weeks beginning no earlier than day +7 after HSCT but beginning no later than 30 days after HSCT. If the patient has not developed >grade I side effects to IL-2 and has not developed >grade I GVHD then the patient may continue the IL-2 for 6 additional weeks. Time will be measured as 'week beginning with first IL-2 injection. | Biological | IL2 Administration |
Primary outcome
Rate of Dose Limiting Toxicities
Time frame: 6-12 weeks
Assessment of the safety and the toxicity of low-dose IL-2, administered according to the dosage described in this protocol, in this group of patients The outcome measure is the proportion of participants with dose limiting toxicities.
2 secondary outcomes
Rate of Severe (Grade III or IV) Acute GVHD
Time frame: Up to 12 weeks on low-dose IL-2
Percentage Change in CD4+ CD25+ FoxP3+ Regulatory T Cells (Tregs) From Pre to Post IL-2 Infusions
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24573552Kennedy-Nasser AA, Ku S, Castillo-Caro P, Hazrat Y, Wu MF, Liu H, Melenhorst J, Barrett AJ, Ito S, Foster A, Savoldo B, Yvon E, Carrum G, Ramos CA, Krance RA, Leung K, Heslop HE, Brenner MK, Bollard CM. Ultra low-dose IL-2 for GVHD prophylaxis after allogeneic hematopoietic stem cell transplantation mediates expansion of regulatory T cells without diminishing antiviral and antileukemic activity. Clin Cancer Res. 2014 Apr 15;20(8):2215-25. doi: 10.1158/1078-0432.CCR-13-3205. Epub 2014 Feb 26.
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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.
Rayne Rouce, MD principal investigator
Baylor College of Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing IL-2 in people with Acute Lymphoblastic Leukemia and ALL, run by Baylor College of Medicine at 2 sites 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 11 inclusion and 7 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: finished, as of the sponsor's last update on 4 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Yes. Results are posted in the registry (first posted 4 Jul 2014). 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?
Rate of Dose Limiting Toxicities (time frame: 6-12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00539695, which also lists 1 linked publication.
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 May 2018.