Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The study will investigate, in children with acute lymphoblastic leukemia during maintenance treatment, if addition of allopurinol to conventional oral 6-mercaptopurine and methotrexate therapy, affects erythrocyte concentrations of 6-thioguanine and 6 methylmercaptopurine. The effect on hematological and liver toxicity parameters in blood will also be investigated as well as clinical toxicity.
After one month of conventional maintenance therapy (MT) children and adolescents, treated for acute lymphoblastic leukemia on Nordic protocols and with wild type thiopurine methyltransferase (TPMT) are eligible for the study. They will first receive a 12 week phase with normal MT during which time repeated sampling of 6-mercaptopurine (6MP) metabolite levels and other laboratory parameters will be performed. After 12 weeks, allopurinol at a dose of 50 mg/sqm is added (simultaneously reducing the dose of 6MP by 50%) and during the next 12 weeks patients are monitored closely for toxicity and samples for determination of metabolite levels and hematological and liver toxicity are obtained regularly. If, after 4 weeks of allopurinol treatment, the levels of 6-thioguanine are below 200 nmol/mmol hemoglobin, the dose of allopurinol will be increased to 100 mg/sqm. Allopurinol treatment is continued for 12 weeks after which the patients switch to their original maintenance therapy.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard maintenance therapy | Active Comparator | Standard maintenance therapy with 6 mercaptopurine and methotrexate |
|
| Allopurinol treatment | Experimental | The second 12 week phase during which allopurinol is added to oral 6-mercaptopurine and methotrexate therapy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Allopurinol | Drug | Allopurinol is added to standard oral 6-mercaptopurine and methotrexate |
|
| Measure | Description | Time Frame |
|---|---|---|
| 6-thioguanine (6TG) levels in erythrocytes | The fraction of patients with 6TG levels over 200 nmol/mmol Hb at week 13 and 25 (ie after 12 weeks standard and allopurinol treatment respectively) | Up to week 25 |
| Measure | Description | Time Frame |
|---|---|---|
| Mean level of 6-thioguanine | The mean level of 6TG at week 13 and 25 | Up to week 25 |
| Mean level of DNA-incorporated thioguanine (DNA-TGN) | The mean level of DNA-TGN at week 13 and 25 |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jonas Abrahamsson, PhD, MD | Contact | +46 707 695159 | vobjab@gmail.com | |
| Torben Ek, PhD, MD | Contact | +46 706 169284 | torben.ek@mac.com |
| Name | Affiliation | Role |
|---|---|---|
| Jonas Abrahamsson, PhD, MD | Childrens Cancer Center, Queen Silvia Children Hospital, Sahlgrenska Academy, Gothenburg, Sweden | Study Chair |
| Riita Niinimäki, PhD, MD | Dept of Pediatrics and Adolescents, Oulu University Hospital, Box 23, 90029 OYS, Finland |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dept of Pediatrics and Adolescents, Oulu University Hospital, Box 23, 90029 OYS, Finland | Not yet recruiting | Oulu | 90029 OYS | Finland |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| ID | Term |
|---|---|
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
Not provided
Not provided
| ID | Term |
|---|---|
| D000493 | Allopurinol |
| ID | Term |
|---|---|
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Standard treatment | Drug | Oral 6-mercaptopurine and methotrexate |
|
| Up to week 25 |
| Mean level of 6-methylmercaptopurine (6MMP) | The mean level of 6MMP at week 13 and 25 | Up to week 25 |
| Mean levels of platelets | Comparison of weighted mean of platelets in the treatment phases | Up to week 25 |
| Mean levels of hemoglobin | Comparison of weighted mean of hemoglobin in the treatment phases | Up to week 25 |
| Mean levels of absolute neutrophil count (ANC) | Comparison of weighted mean of ANC in the treatment phases | Up to week 25 |
| Mean levels of white blood cells (WBC) | Comparison of weighted mean of WBC in the treatment phases | Up to week 25 |
| Glutamate pyruvate transaminase (GPT) | Comparison of weighted means of serum GPT in the treatment phases | Up to week 25 |
| Bilirubin | Comparison of weighted means of serum bilirubin in the treatment phases | Up to week 25 |
| Hypoglycemia | Comparison of incidence of hypoglycemia and laboratory measures of metabolic disturbance during the treatment phases | Up to week 25 |
| Metabolic disturbance | Comparison of incidence of laboratory measures of metabolic disturbance during the treatment phases | Up to week 25 |
| Incidence of serious adverse events (SAE) | Comparison of the frequency of SAE in the treatment phases | Up to week 29 |
| Cumulative dose of 6-mercaptopurine and methotrexate | Comparison of the cumulative dose of 6MP and methotrexate and days with treatment interruption in the two treatment arms | Up to week 29 |
| Childrens' Cancer Centre, Queen Silvias Childrens and Adolescents Hospital | Recruiting | Gothenburg | 416 85 | Sweden |
|
| Linköping University Hospital, Dept of Pediatrics | Not yet recruiting | Linköping | 58185 | Sweden |
|
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |