Study of Sequential Administration of Oral 6-Thioguanine After Methotrexate in Patients With LCH
Study Details
Study Description
Brief Summary
The objective of this study is to determine the incidence of complete and partial response and the duration of response in patients with Langerhans Cell Histiocytosis (LCH) treated with sequential administration of oral 6-Thioguanine (6-TG) after Methotrexate (MTX).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1 MTX, 6-TG, Leucovorin |
Drug: Methotrexate
MTX 30mg/m2 (or 1mg/kg for infants) orally, given in three equally divided doses at 0,8, and 16hrs
Other Names:
Drug: 6-Thioguanine
6-TG 300mg/m2 (or 10mg/kg for infants) orally, given in one dose.
Other Names:
Drug: Leucovorin Calcium
5mg orally at 36,48, and 60hrs (or 12 hrs after the dose of 6-TG and then every 12 hrs for a total of 3 doses)
|
Outcome Measures
Primary Outcome Measures
- Determine the Incidence of Complete and Partial Response and the Duration of Response in Patients With Langerhans Cell Histiocytosis (LCH) Treated With Sequential Administration of Oral 6-TG After MTX. [Conclusion of the study]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients with histologic proof of LCH who have multifocal or multisystem disease involvement.
-
Patients must have a life expectancy of at least 8 weeks.
-
All patients must have ECOG performance level rating of-< 2.
-
Patients or their parents (guardian) must sign an informed consent indicating that they are aware of the investigational nature of the study, using commercially available drugs.
-
Patients must have recovered from the toxic effects of prior therapy before entering this study or at least 2 weeks should have elapsed since the end of last course of chemotherapy.
-
Patients must have adequate liver function (bilirubin < 2.0 mg/dl, SGOT less than 1.5 times normal (unless it is due to disease), adequate renal function (creatinine < 1.5 mg/dl, creatinine clearance >_ 60 ml/min/1.73 m2) and normal electrolytes.
-
Patients should have a granulocyte count > 500/uL and a platelet count >_ 100,000/uL (unless due to disease involvement of the bone marrow).
-
Male and female patients of child-bearing age should use effective methods of contraception, if sexually active.
Exclusion Criteria:
- Patients with active infections or significant medical conditions other than their disease (LCH) shall be excluded.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Memorial Sloan-Kettering Cancer Center | New York | New York | United States | 10065 |
Sponsors and Collaborators
- Memorial Sloan Kettering Cancer Center
Investigators
- Principal Investigator: Tanya Trippett, MD, Memorial Sloan Kettering Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 94-132
Study Results
Participant Flow
| Recruitment Details | Protocol Open to Accrual: 01/10/1995 Protocol Closed to Accrual: 07/25/2006 Primary Completion Date (if applicable): 06/09/2009 Recruitment Location is the medical clinic |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | MTX, 6-TG and Leucovorin |
|---|---|
| Arm/Group Description | Methotrexate: MTX 30mg/m2 (or 1mg/kg for infants) orally, given in three equally divided doses at 0,8, and 16hrs 6-Thioguanine: 6-TG 300mg/m2 (or 10mg/kg for infants) orally, given in one dose. Leucovorin Calcium: 5mg orally at 36,48, and 60hrs (or 12 hrs after the dose of 6-TG and then every 12 hrs for a total of 3 doses) |
| Period Title: Overall Study | |
| STARTED | 5 |
| COMPLETED | 5 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | MTX, 6-TG and Leucovorin |
|---|---|
| Arm/Group Description | Methotrexate: MTX 30mg/m2 (or 1mg/kg for infants) orally, given in three equally divided doses at 0,8, and 16hrs 6-Thioguanine: 6-TG 300mg/m2 (or 10mg/kg for infants) orally, given in one dose. Leucovorin Calcium: 5mg orally at 36,48, and 60hrs (or 12 hrs after the dose of 6-TG and then every 12 hrs for a total of 3 doses) |
| Overall Participants | 5 |
| Age (Count of Participants) | |
| <=18 years |
4
80%
|
| Between 18 and 65 years |
1
20%
|
| >=65 years |
0
0%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
3
60%
|
| Male |
2
40%
|
| Region of Enrollment (participants) [Number] | |
| United States |
5
100%
|
Outcome Measures
| Title | Determine the Incidence of Complete and Partial Response and the Duration of Response in Patients With Langerhans Cell Histiocytosis (LCH) Treated With Sequential Administration of Oral 6-TG After MTX. |
|---|---|
| Description | |
| Time Frame | Conclusion of the study |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | MTX, 6-TG and Leucovorin |
|---|---|
| Arm/Group Description | Methotrexate: MTX 30mg/m2 (or 1mg/kg for infants) orally, given in three equally divided doses at 0,8, and 16hrs 6-Thioguanine: 6-TG 300mg/m2 (or 10mg/kg for infants) orally, given in one dose. Leucovorin Calcium: 5mg orally at 36,48, and 60hrs (or 12 hrs after the dose of 6-TG and then every 12 hrs for a total of 3 doses) |
| Measure Participants | 5 |
| Complete Response |
2
40%
|
| Stable Disease |
1
20%
|
| Progression of Disease |
2
40%
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | MTX, 6-TG and Leucovorin | |
| Arm/Group Description | Methotrexate: MTX 30mg/m2 (or 1mg/kg for infants) orally, given in three equally divided doses at 0,8, and 16hrs 6-Thioguanine: 6-TG 300mg/m2 (or 10mg/kg for infants) orally, given in one dose. Leucovorin Calcium: 5mg orally at 36,48, and 60hrs (or 12 hrs after the dose of 6-TG and then every 12 hrs for a total of 3 doses) | |
All Cause Mortality |
||
| MTX, 6-TG and Leucovorin | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| MTX, 6-TG and Leucovorin | ||
| Affected / at Risk (%) | # Events | |
| Total | 2/5 (40%) | |
| General disorders | ||
| Fever | 1/5 (20%) | 1 |
| Investigations | ||
| Neutrophil count decreased | 1/5 (20%) | 1 |
| Platelet count decreased | 1/5 (20%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| MTX, 6-TG and Leucovorin | ||
| Affected / at Risk (%) | # Events | |
| Total | 5/5 (100%) | |
| Blood and lymphatic system disorders | ||
| Anemia | 4/5 (80%) | 10 |
| Gastrointestinal disorders | ||
| Abdominal pain/cramping | 1/5 (20%) | 1 |
| Diarrhea | 1/5 (20%) | 1 |
| Nausea | 1/5 (20%) | 1 |
| Investigations | ||
| Blood bilirubin increased | 1/5 (20%) | 1 |
| Creatinine increased | 1/5 (20%) | 1 |
| White blood cell decreased | 2/5 (40%) | 4 |
| Neutrophil count decreased | 1/5 (20%) | 1 |
| Platelet count decreased | 2/5 (40%) | 9 |
| Metabolism and nutrition disorders | ||
| Anorexia | 1/5 (20%) | 1 |
| Hypomagnesemia | 1/5 (20%) | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Bone pain | 1/5 (20%) | 1 |
| Nervous system disorders | ||
| Headache | 1/5 (20%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Sore throat | 1/5 (20%) | 2 |
| Skin and subcutaneous tissue disorders | ||
| Rash desquamation | 1/5 (20%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Tanya Trippett |
|---|---|
| Organization | Memorial Sloan Kettering Cancer Center |
| Phone | 212-639-8267 |
| trippet1@mskcc.org |
- 94-132