Chronic Myelogenous LeukemiaPhase 4NCT01901666
Assessment Of Gh-Igf-1 Axis In Children With Chronic Myelogenous Leukemia (CML) In Remission
A Phase 4 study testing Growth Hormone in people with Chronic Myelogenous Leukemia and Short Stature, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
Trial summary
CML is a myeloproliferative disorder defined by the presence of the Philadelphia chromosome, which arises from the reciprocal translocation of genes on chromosomes 9 and 22.It is rare in childhood and accounts for 2-3% of all leukemias in childhood. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Chronic Myelogenous Leukemia, Short Stature
- What is being tested?
- Growth Hormone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteIndia
- Study dates
- Jan 2013to Dec 2014
- Phase
- Phase 4
- 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
Who may be able to join
- CML patients on Imatinib therapy for more than 6 months and in remission will be included in the study if there is
- severe short stature (height SDS <-3 SD)
- severe growth deceleration (height velocity <-2 SD over 12 months)
- Height <-2 SD and height velocity <-1.0 SD over 12 months
- Height <-1.5 SD and height velocity <-1.5 SD over 2 years
Who cannot join
- Patients with coexisting systemic illness(e.g. kidney disease, liver disease, celiac disease).
- Patients of CML not receiving Imatinib therapy as prescribed (poor compliance).
Trial locations and contacts
1 site in 1 country.
India1 site, 1 recruiting
- Recruiting
Postgraduate Institute of Medical Education and Research
Chandigarh, Uttarakhand, 160012
anil bhansali, MBBS,MD,DM, 9316977995, anilbhansaliendocrine@rediffmail.com
About this study
Official title: ASSESSMENT OF GH-IGF1 AXIS AND TO STUDY RESPONSE TO GH THERAPY IN CHILDREN WITH CML IN REMISSION HAVING GH DEFICIENCY
CML is a myeloproliferative disorder defined by the presence of the Philadelphia chromosome, which arises from the reciprocal translocation of genes on chromosomes 9 and 22.It is rare in childhood and accounts for 2-3% of all leukemias in childhood.
BCR-ABL gene on Philadelphia chromosome results in a 210kd fused BCR-ABL protein with constitutive tyrosine kinase activity, and subsequent activation of cytoplasmic and nuclear signal transduction pathways including STAT, RAS, JUN, MYC, and phosphatidylinositol-3 kinase. The ultimate result of such activation is the myeloid proliferation and differentiation and suppressed apoptosis.
Read more
Children present with a higher WBC count, otherwise presentation is nearly identical to adults. Current treatment include tyrosine kinase inhibitors (TKI) and allogeneic stem cell transplant (SCT).Imatinibmesylate inhibits the tyrosine kinase (TK) activity of BCR-ABL1 and several related TKs, including c-kit and the platelet-derived growth factor receptor (PDGFR). Development of tyrosine kinase inhibitor (TKI) therapy has revolutionizedtreatment of CML. Imatinib or second generation TKIs (dasatinib or nilotinib) have become standard front-line therapy forchildren and adults with CML and are also important componentsof therapy for Ph+ acute lymphoblastic leukemia (ALL).
TKIs are administered orally and cause a number of side effects including fatigue, hypertension, rash, impaired wound healing, myelosuppression, and diarrhea . The overall toxicity of TKIs, while less life-threatening than conventional cytotoxic chemotherapy, nevertheless is common, and may require dose reduction.Recently, proposed endocrine-related side effects of these agents include alterations in thyroid function, bone metabolism, linear growth, gonadal function, fetal development, glucose metabolism and adrenal function.
Growth impairment is one of the major adverse effect of long-term imatinib treatment in children with CML. Multiple case reports have demonstrated growth retardation in children onimatinib.Imatinibmesylate inhibits the TK activity of BCR-ABL1 and several related TKs, including c-kit and theplatelet-derived growth factor receptor (PDGFR). It isthe inhibition of TK activity at the non-BCR-ABL sites that couldbe the likely cause for the adverse effect on growth. Severalstudies in adults have suggested that inhibition of c-kit,c-fms, and PDGF receptors results in modulation of bone metabolism. Other reports are focusing on disturbance of the growth hormone (GH) axis as a mechanism for growth impairment. Receptor and non receptor TK is expressed at multiple levels in GH-IGF-1 axis including GHRH-R, GH-R and IGF-1R. Inhibition of TKs with TKI, at any one of these level, might result in growth impairment.
Various studies are available to show that Imainib therapy may cause short stature in children on prolonged treatment but exact mechanism by which this occurs is still not clear. Further, no treatment modality has been tried so far, for short stature in these children.
So, the purpose of this study is to study GH-IGF1 axis in these children and to administer GH therapy to GH deficienct children in remission.
Read the detailed description
AIMS AND OBJECTIVES:
- To study GH-IGF1 axis in children with CML having short stature following Imatinib therapy.
- To administer growth hormone therapy to children with CML on Imatinib in remission having GH deficiency.
STUDY DESIGN: It is an interventional, non-randomized study. STUDY GROUP: one NUMBER OF PATIENTS: 20
ELIGIBILITY CRITERIA:
CML patients on Imatinib therapy for more than 6 months and in remission will be included in the study if there is:
- Severe short stature (height SDS <-3 SD)
- Severe growth deceleration (height velocity SDS <-2 SD over 12 months)
- Height <-2 SD and height velocity <-1.0 SD over 12 months
- Height <-1.5 SD and height velocity <-1.5 SD over 2 years
EXCLUSION CRITERIA:
- Patients with coexisting systemic illness (e.g. kidney disease, liver disease, celiac disease)
- Patients of CML not receiving Imatinib therapy as prescribed. (e.g. poor compliance)
MATERIALS AND METHODS:
Once eligibility criteria are confirmed, after having written informed consent, following parameters will be assessed:
- Chronological age
- Height
- Height for age
- Height SDS
- Target height
- Body proportion
- Weight
- Weight for age
Following investigations will be done in all patients:
- Complete blood count with peripheral smear.
- Liver function tests
- Renal function tests
- Calcium, phosphate, ALP, albumin.
- Fasting Blood glucose
- Thyroid function tests (T4, and TSH)
- Serum Cortisol
- Serum Prolactin
- Serum Follicular stimulating hormone (FSH) and Luteinizing hormone (LH)
- Serum Testosterone
- Serum Estrogen
- Serum IgA anti-tTG antibodies
- Serum IGF-1.
- Serum IGFBP-3.
- X-Ray of left hand and wrist
- MRI Brain focussing pituitary hypothalamic region. Two dynamic growth hormone provocation,GHRH + Arginine andGlucagon tests will be performed in all patients having no other cause for short stature.Minimum gap of one week will be kept between the two GHstimulationtests.Priming will be done prior to each GH stimulation test. IGF-1 generation test will be performed in all patients.Minimum gap of one week will be kept betweenGH stimulation and IGF-1 generation test.
X-ray of left hand and wrist for bone age and sexual maturity rating (SMR) by Tanners scale will be performed for all patients. All GH deficient patients with bone age <14 years will be treated with GH therapy for one year. 0.3mg/kg/week GH in seven divided doses will be given subcutaneously. Serum IGF-1 will be measured 4weekly and GH dose will be titrated till S.IGF-1 is in mid-normal range and then after every 3 months.
Patients will be monitored for any side effects of GH therapy Growth parameters, Serum T4, TSH and complete blood count will be assessed after every 3 months.Cytogenetic and molecular remission will be assessed before and after completion of GH therapy.
- Conditions
- Chronic Myelogenous Leukemia, Short Stature
- Being tested
- Growth Hormone
- Keywords
- growth hormone, Chronic Myelogenous Leukemia, Imatinib,serum IGF-1
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Dwarfism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Growth HormoneDrug
Also called Recombinant human growth hormone
All GH deficient patients with bone age <14 years will be treated with GH therapy for one year.Serum IGF-1 will be measured 4weekly and GH dose will be titrated till S.IGF-1 is in mid-normal range and then after every 3 months.
Growth parameters will be assessed after every 3 months.Serum T4, TSH will be done after every 3 months. Patients will be monitored for any side effects of GH therapy
| Study group | Role | What they receive |
|---|---|---|
| Growth hormone deficient group | Experimental | 0.3mg/kg/week GH in seven divided doses will be given subcutaneously for one year. Receives: Drug: Growth Hormone |
What is being measured
The primary outcome is the main question the study is designed to answer.
To know whether patients of CML who are faltering on growth after imatinib therapy are GH deficient or having GH resistance by performing GH provocation tests and IGF-1 generation test.
Growth impairment is one of the major adverse effect of long-term imatinib treatment in children with CML. Receptor and non receptor TK is expressed at multiple levels in GH-IGF-1 axis including GHRH-R, GH-R and IGF-1R. Inhibition of TKs with TKI, at any one of these level, might result in growth impairment.Various studies are available to show that Imainib therapy may cause short stature in children on prolonged treatment but exact mechanism by which this occurs is still not clear.So, the purpose of this study is to study GH-IGF1 axis in these children
Measured: 30 months
Secondary outcomes (1)
To administer growth hormone therapy to children with CML on Imatinib in remission having GH deficiency and to measure IGF-1 levels, gain in height and height velocity on GH therapy.
Disturbance of the growth hormone (GH) axis has been shown as one of the mechanism for growth impairment. But, no treatment modality has been tried so far for short stature in these children. So, one of the outcome measure will be to study gain in height after administeration of GH therapy to these GH deficient children.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2013 (estimated)
- Study startJan 2013
- Primary completionJun 2014 (estimated)
- Study completionDec 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Myelogenous LeukemiaStudies of the same condition, open and under way.
- 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
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, Chandigarh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, dr anuradha aggarwal, Post Graduate Institute of Medical Education and Research, Chandigarh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01901666
- Sponsor's protocol ID
- GH-IGF-1 AXIS AND CML
- Status last verified
- Jul 2013
- First submitted
- 29 Jun 2013
- Last updated
- 17 Jul 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ASSESSMENT OF GH-IGF1 AXIS AND TO STUDY RESPONSE TO GH THERAPY IN CHILDREN WITH CML IN REMISSION HAVING GH DEFICIENCY
- ClinicalTrials.gov ID
- NCT01901666
- Acronym / sponsor ID
- GH-IGF-1 AXIS AND CML
- Conditions
- Chronic Myelogenous Leukemia, Short Stature
- Keywords
- growth hormone, Chronic Myelogenous Leukemia, Imatinib,serum IGF-1
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, ChandigarhUniversity, hospital or other
- Study start
- Jan 2013
- Primary completion
- Jun 2014 (estimated)
- Study completion
- Dec 2014 (estimated)
- First posted
- 17 Jul 2013 (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.
CML is a myeloproliferative disorder defined by the presence of the Philadelphia chromosome, which arises from the reciprocal translocation of genes on chromosomes 9 and 22.It is rare in childhood and accounts for 2-3% of all leukemias in childhood.
BCR-ABL gene on Philadelphia chromosome results in a 210kd fused BCR-ABL protein with constitutive tyrosine kinase activity, and subsequent activation of cytoplasmic and nuclear signal transduction pathways including STAT, RAS, JUN, MYC, and phosphatidylinositol-3 kinase. The ultimate result of such activation is the myeloid proliferation and differentiation and suppressed apoptosis.
Children present with a higher WBC count, otherwise presentation is nearly identical to adults. Current treatment include tyrosine kinase inhibitors (TKI) and allogeneic stem cell transplant (SCT).Imatinibmesylate inhibits the tyrosine kinase (TK) activity of BCR-ABL1 and several related TKs, including c-kit and the platelet-derived growth factor receptor (PDGFR). Development of tyrosine kinase inhibitor (TKI) therapy has revolutionizedtreatment of CML. Imatinib or second generation TKIs (dasatinib or nilotinib) have become standard front-line therapy forchildren and adults with CML and are also important componentsof therapy for Ph+ acute lymphoblastic leukemia (ALL).
TKIs are administered orally and cause a number of side effects including fatigue, hypertension, rash, impaired wound healing, myelosuppression, and diarrhea . The overall toxicity of TKIs, while less life-threatening than conventional cytotoxic chemotherapy, nevertheless is common, and may require dose reduction.Recently, proposed endocrine-related side effects of these agents include alterations in thyroid function, bone metabolism, linear growth, gonadal function, fetal development, glucose metabolism and adrenal function.
Growth impairment is one of the major adverse effect of long-term imatinib treatment in children with CML. Multiple case reports have demonstrated growth retardation in children onimatinib.Imatinibmesylate inhibits the TK activity of BCR-ABL1 and several related TKs, including c-kit and theplatelet-derived growth factor receptor (PDGFR). It isthe inhibition of TK activity at the non-BCR-ABL sites that couldbe the likely cause for the adverse effect on growth. Severalstudies in adults have suggested that inhibition of c-kit,c-fms, and PDGF receptors results in modulation of bone metabolism. Other reports are focusing on disturbance of the growth hormone (GH) axis as a mechanism for growth impairment. Receptor and non receptor TK is expressed at multiple levels in GH-IGF-1 axis including GHRH-R, GH-R and IGF-1R. Inhibition of TKs with TKI, at any one of these level, might result in growth impairment.
Various studies are available to show that Imainib therapy may cause short stature in children on prolonged treatment but exact mechanism by which this occurs is still not clear. Further, no treatment modality has been tried so far, for short stature in these children.
So, the purpose of this study is to study GH-IGF1 axis in these children and to administer GH therapy to GH deficienct children in remission.
Detailed description
AIMS AND OBJECTIVES:
- To study GH-IGF1 axis in children with CML having short stature following Imatinib therapy.
- To administer growth hormone therapy to children with CML on Imatinib in remission having GH deficiency.
STUDY DESIGN: It is an interventional, non-randomized study. STUDY GROUP: one NUMBER OF PATIENTS: 20
ELIGIBILITY CRITERIA:
CML patients on Imatinib therapy for more than 6 months and in remission will be included in the study if there is:
- Severe short stature (height SDS <-3 SD)
- Severe growth deceleration (height velocity SDS <-2 SD over 12 months)
- Height <-2 SD and height velocity <-1.0 SD over 12 months
- Height <-1.5 SD and height velocity <-1.5 SD over 2 years
EXCLUSION CRITERIA:
- Patients with coexisting systemic illness (e.g. kidney disease, liver disease, celiac disease)
- Patients of CML not receiving Imatinib therapy as prescribed. (e.g. poor compliance)
MATERIALS AND METHODS:
Once eligibility criteria are confirmed, after having written informed consent, following parameters will be assessed:
- Chronological age
- Height
- Height for age
- Height SDS
- Target height
- Body proportion
- Weight
- Weight for age
Following investigations will be done in all patients:
- Complete blood count with peripheral smear.
- Liver function tests
- Renal function tests
- Calcium, phosphate, ALP, albumin.
- Fasting Blood glucose
- Thyroid function tests (T4, and TSH)
- Serum Cortisol
- Serum Prolactin
- Serum Follicular stimulating hormone (FSH) and Luteinizing hormone (LH)
- Serum Testosterone
- Serum Estrogen
- Serum IgA anti-tTG antibodies
- Serum IGF-1.
- Serum IGFBP-3.
- X-Ray of left hand and wrist
- MRI Brain focussing pituitary hypothalamic region. Two dynamic growth hormone provocation,GHRH + Arginine andGlucagon tests will be performed in all patients having no other cause for short stature.Minimum gap of one week will be kept between the two GHstimulationtests.Priming will be done prior to each GH stimulation test. IGF-1 generation test will be performed in all patients.Minimum gap of one week will be kept betweenGH stimulation and IGF-1 generation test.
X-ray of left hand and wrist for bone age and sexual maturity rating (SMR) by Tanners scale will be performed for all patients. All GH deficient patients with bone age <14 years will be treated with GH therapy for one year. 0.3mg/kg/week GH in seven divided doses will be given subcutaneously. Serum IGF-1 will be measured 4weekly and GH dose will be titrated till S.IGF-1 is in mid-normal range and then after every 3 months.
Patients will be monitored for any side effects of GH therapy Growth parameters, Serum T4, TSH and complete blood count will be assessed after every 3 months.Cytogenetic and molecular remission will be assessed before and after completion of GH therapy.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Growth hormone deficient group | Experimental | Drug: Growth Hormone0.3mg/kg/week GH in seven divided doses will be given subcutaneously for one year. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- CML patients on Imatinib therapy for more than 6 months and in remission will be included in the study if there is
- severe short stature (height SDS <-3 SD)
- severe growth deceleration (height velocity <-2 SD over 12 months)
- Height <-2 SD and height velocity <-1.0 SD over 12 months
- Height <-1.5 SD and height velocity <-1.5 SD over 2 years
Key exclusion criteria (2 listed)
- Patients with coexisting systemic illness(e.g. kidney disease, liver disease, celiac disease).
- Patients of CML not receiving Imatinib therapy as prescribed (poor compliance).
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 |
|---|---|---|
| Growth HormoneAlso: Recombinant human growth hormoneAll GH deficient patients with bone age <14 years will be treated with GH therapy for one year.Serum IGF-1 will be measured 4weekly and GH dose will be titrated till S.IGF-1 is in mid-normal range and then after every 3 months. Growth parameters will be assessed after every 3 months.Serum T4, TSH will be done after every 3 months. Patients will be monitored for any side effects of GH therapy | Drug | Growth hormone deficient group |
Primary outcome
To know whether patients of CML who are faltering on growth after imatinib therapy are GH deficient or having GH resistance by performing GH provocation tests and IGF-1 generation test.
Time frame: 30 months
Growth impairment is one of the major adverse effect of long-term imatinib treatment in children with CML. Receptor and non receptor TK is expressed at multiple levels in GH-IGF-1 axis including GHRH-R, GH-R and IGF-1R. Inhibition of TKs with TKI, at any one of these level, might result in growth impairment.Various studies are available to show that Imainib therapy may cause short stature in children on prolonged treatment but exact mechanism by which this occurs is still not clear.So, the purpose of this study is to study GH-IGF1 axis in these children
1 secondary outcome
To administer growth hormone therapy to children with CML on Imatinib in remission having GH deficiency and to measure IGF-1 levels, gain in height and height velocity on GH therapy.
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2013.
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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.
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 Growth Hormone in people with Chronic Myelogenous Leukemia and Short Stature, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
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 5 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 17 Jul 2013. 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 India. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact ANIL BHANSALI, MBBS, MD,DM (9316977995, anilbhansaliendocrine@rediffmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To know whether patients of CML who are faltering on growth after imatinib therapy are GH deficient or having GH resistance by performing GH provocation tests and IGF-1 generation test. (time frame: 30 months). 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 Jul 2013.