Total Therapy for Infants With Acute Lymphoblastic Leukemia (ALL) I

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

Total Therapy for Infants With Acute Lymphoblastic Leukemia (ALL) I

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02553460
• Other study ID #: TINI
• Secondary ID: NCI-2015-01493
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: January 29, 2016
• Est. completion date: October 2031

Study information

• Verified date: January 2024
• Source: St. Jude Children's Research Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to test the good and bad effects of the study drugs bortezomib and vorinostat when they are given in combination with chemotherapy commonly used to treat acute lymphoblastic leukemia (ALL) in infants. For example, adding these drugs could decrease the number of leukemia cells, but it could also cause additional side effects. Bortezomib and vorinostat have been approved by the US Food and Drug Administration (FDA) to treat other cancers in adults, but they have not been approved for treating children with leukemia. With this research, we plan to meet the following goals:

PRIMARY OBJECTIVE:

• Determine the tolerability of incorporating bortezomib and vorinostat into an ALL chemotherapy backbone for newly diagnosed infants with ALL.

SECONDARY OBJECTIVES:

• Estimate the event-free survival and overall survival of infants with ALL who are treated with bortezomib and vorinostat in combination with an ALL chemotherapy backbone.

• Measure minimal residual disease (MRD) positivity using both flow cytometry and PCR.

• Compare end of induction, end of consolidation, and end of reinduction MRD levels to Interfant99 (ClinicalTrials.gov registration ID number NCT00015873) participant outcomes.

Description:

Treatment will consist of 4 main phases: Remission Induction, Consolidation, Reinduction, and Maintenance. High risk patients will receive a reintensification phase prior to transplant in first remission.

REMISSION INDUCTION: Chemotherapy will be given in an attempt to induce the participant's leukemia into remission. Drugs given are intrathecal triple drug treatment with methotrexate, hydrocortisone and Ara-C (ITMHA); dexamethasone; vorinostat; bortezomib; PEG-asparaginase; mitoxantrone; cyclophosphamide; cytarabine; and 6-mercaptopurine.

CONSOLIDATION PHASE: After the participant's blood counts have recovered from Remission Induction, he/she will move to the consolidation phase. This therapy is given to kill any remaining leukemia cells. Drugs given are ITMHA, high-dose methotrexate, and 6-mercaptopurine.

RE-INDUCTION: This phase aims to improve the participant's overall response to therapy by again seeking to bring his/her leukemia into remission. Drugs given are ITMHA, mitoxantrone, peg-asparaginase, dexamethasone, bortezomib, and vorinostat.Participants that achieve MRD negative status following Re-Induction may proceed directly to stem cell transplant (SCT) (SCT not part of this study).

RE-INTENSIFICATION: Participants that remain MRD positive following Consolidation or Reinduction may receive Chimeric Antigen Receptor T-Cell therapy (CART), if available (CART is not part of this study), or proceed to a Reintensification phase then go on to stem cell transplant (SCT).

MAINTENANCE PHASE: Participants with negative MRD after consolidation will skip the re-intensification phase and proceed to receive maintenance therapy to keep the leukemia from returning. Drugs given are ITMHA, dexamethasone, vincristine, 6-mercaptopurine and methotrexate. Each cycle of these drugs lasts 28 days and will be repeated up to 20 times as long as there are no serious side effects.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: October 2031
• Est. primary completion date: May 10, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 365 Days

Eligibility

Inclusion Criteria:

• Patient is = 365 days of age at the time of diagnosis.

• Patient has newly diagnosed acute lymphoblastic leukemia (ALL) or acute undifferentiated leukemia with =25% blasts in the bone marrow (M3), with or without extramedullary disease. Patients with T-cell ALL are eligible. Patients with bilineage or biphenotypic acute leukemia are eligible, provided the morphology and immunophenotype are predominantly lymphoid.

• Limited prior therapy, including hydroxyurea for 72 hours or less, systemic glucocorticoids for one week or less, one dose of vincristine, and one dose of intrathecal chemotherapy.

• Written informed consent following Institutional Review Board, NCI, FDA, and Office for Human Research Protections (OHRP) Guidelines.

Exclusion Criteria:

• Patients with prior therapy, other than therapy specified in the Inclusion Criteria.

• Patients with mature B-cell ALL or acute myelogenous (AML).

• Patients with Down syndrome.

• Inability or unwillingness of legal guardian/representative to give written informed consent.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• ITMHA
Given intrathecally (IT).
• Dexamethasone
Given orally (PO) or naso-gastrically (NG) or intravenously (IV).
• Mitoxantrone
Given IV.
• Pegaspargase
Given IV. If participant is allergic to pegaspargase, Asparaginase Erwinia Chrysanthemi will be used.
• Asparaginase Erwinia Chrysanthemi
Asparaginase Erwinia Chrysanthemi will be used in case of allergy or intolerance of participant to PEG-asparaginase. Given IV (preferred) or intramuscularly (IM).
• Bortezomib
Given IV.
• Vorinostat
Taken PO or NG.
• Cyclophosphamide
Given IV.
• Mercaptopurine
Given PO or NG.
• Methotrexate
Given IV, IM or PO.
• Leucovorin Calcium
Leucovorin rescue PO or IV.
• Cytarabine
Given IV.
• Etoposide
Given IV. In case of participant allergy, etoposide phosphate (Etopophos®) will be given.
• Vincristine
Given IV.

Locations

Country	Name	City	State
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	Stollery Children's Hospital	Edmonton	Alberta
Canada	McMaster Children's Hospital at Hamilton Health Sciences	Hamilton	Ontario
Canada	Centre Hospitalier Universitaire Sainte-Justine	Montreal	Quebec
Canada	The Montreal Children's Hospital (MUHC-McGill)	Montreal	Quebec
Canada	Centre Hospitalier Universitaire de Quebec	Québec	Quebec
Canada	Children's & Women's Health Centre of British Columbia	Vancouver	British Columbia
United States	St. Jude Affiliate-Charlotte	Charlotte	North Carolina
United States	Cincinnati Children's Hospital	Cincinnati	Ohio
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Children's Hospital and Clinics of Minnesota	Minneapolis	Minnesota
United States	Children's Hospital of the King's Daughters (CHKD)	Norfolk	Virginia
United States	Children's Hospital of Orange County	Orange	California
United States	Lucile Packard Children's Hospital Stanford University	Palo Alto	California
United States	Oregon Health and Science University	Portland	Oregon
United States	Rady Children's Hospital and Health Center	San Diego	California

Sponsors (3)

Lead Sponsor	Collaborator
St. Jude Children's Research Hospital	Baylor College of Medicine, Gateway for Cancer Research

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Treatment-related Mortality (TRM)	Number of treatment related deaths divided by total number of patients during induction or reinduction therapy.; Presented as percentage	At the end of reinduction (up to 5 months after start of therapy)
Secondary	3-year Event Free Survival (EFS)	Event-free survival (EFS) will be estimated by the Kaplan-Meier estimator. For EFS, relapse and second malignancies will be considered as failures in addition to death in complete remission. The time to EFS will be set to 0 for patients who fail to achieve complete remission. EFS probability will be estimated with 95% confidence intervals.	3 years after completion of therapy (up to 5 years after start of therapy)
Secondary	5-year Overall Survival (OS)	Overall survival (OS) will be estimated by the Kaplan-Meier estimator. OS probability at years 3, 5, 10 will be estimated with 95% confidence intervals.	5 years after completion of therapy (up to 7 years after start of therapy)
Secondary	Minimal Residual Disease (MRD) Positivity Using Flow Cytometry at Day 22, End of Induction, End of Consolidation, and End of Maintenance.	Proportion of participants with positive MRD at the end of each therapy block.	At end of induction (approximately 6 weeks), end of consolidation (approximately 14 weeks), end of reinduction (approximately 19 weeks), end of reintensification (approximately 23 weeks), and end of maintenance therapy (approximately 2 years)
Secondary	Minimal Residual Disease (MRD) Positivity Using PCR End of Induction, End of Consolidation, and End of Maintenance.	Proportion of participants with positive MRD at the end of each therapy block.	At end of induction (approximately 6 weeks), end of consolidation (approximately 14 weeks), end of reinduction (approximately 19 weeks), end of reintensification (approximately 23 weeks), and end of maintenance therapy (approximately 2 years)

External Links

•   Clinical Trials Open at St. Jude
•   St. Jude Children's Research Hospital