RECRUITING

Ruxolitinib and Chemotherapy in Adolescents and Young Adults With Ph-like Acute Lymphoblastic Leukemia

Conditions

Acute Lymphoblastic Leukemia ALL, Childhood ALL

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This study will test if adding ruxolitinib to standard multi-drug chemotherapy regimen will be safe and tolerated in adolescents and young adults with newly diagnosed Ph-like acute lymphoblastic leukemia (ALL).

Official Title

Phase I Trial of Ruxolitinib in Combination With a Pediatric Based-regimen for Adolescents and Young Adults (AYAs) With Ph-like Acute Lymphoblastic Leukemia (ALL)

Quick Facts

Study Start:2019-05-28

Study Completion:2027-09-05

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03571321

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 39 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT

Inclusion Criteria	Exclusion Criteria
* Newly diagnosed de novo B-precursor acute lymphoblastic leukemia (ALL) as determined by World Health Organization (WHO) criteria. Patients must have unequivocal diagnosis of precursor B ALL. This includes an institutional immunophenotyping report that is to assign B-lineage or T-lineage. * "Ph-like" signature, as determined by low density micro-array (LDA) card * Jak-targetable genetic signature as defined by any of the following: * Cytokine receptor-like factor 2 (CRLF2) rearranged (JAK2 mutant or wild-type) * JAK2 or erythropoietin receptor (EPOR) fusions. * Other JAK pathway alterations at the discretion of the principle investigator including, but not limited to: * SH2B adaptor protein 3 (SH2B3) deletions * Interleukin-7 receptor subunit alpha (IL7RA) mutations * Prior therapy * Prior to starting ruxolitinib, patients must have completed a 4-drug induction regimen with intrathecal chemotherapy (modified aBFM regimen or equivalent) as per the institutional standard of care. Recommended induction treatment is outlined in Section 5.1.2. * No additional prior therapy for acute leukemia except emergency therapy (corticosteroids or hydroxyurea) for blast cell crisis, superior vena cava syndrome, or renal failure due to leukemic infiltration of the kidneys. When indicated, leukapheresis or exchange transfusion is recommended to reduce the white blood cell count (WBC). * Screening may occur at any point prior to or during induction therapy * Age ≥ 18 years and \< 40 years. Because this is specifically a study of the adolescent and young adult population and no adverse event data are currently available on the use of this pediatric-based chemotherapy regimen in patients ≥ 40 years of age, older adults are excluded from this study, but may be eligible for future trials. * Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Karnofsky ≥ 60%) * Platelet count \> 25,000/uL. * Patients must have normal organ function as defined below: * total bilirubin ≤ 2 mg/dL * aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 2.5 × institutional upper limit of normal * creatinine within normal institutional limits OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal. * Because the therapeutic agents used in this study are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation. * Ability to understand and the willingness to sign a written informed consent document.	* Patients who are receiving any other investigational agent. * Patients with a "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for ≥ 3 years. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to ruxolitinib or other agents used in study. * Use of any potent cytochrome P450 (CYP) 3A4 inhibitor or inducer within 5 half-lives before the first dose of the study drug. Potent inhibitors of CYP3A4 include systemic ketoconazole, posaconazole, voriconazole, clarithromycin, itraconazole, nefazodone, and telithromycin. At the fluconazole dose of 200mg daily used this regimen, there is minimal inhibition of CYP3A4 \[36\] and therefore fluconazole is not prohibited on this trial and no dose modifications should be made in the presence of fluconazole. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Pregnant women are excluded from this study because ruxolitinib is a class C agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ruxolitinib breastfeeding should be discontinued if the mother is treated with ruxolitinib. These potential risks may also apply to other agents used in this study. * Down Syndrome due to the likelihood of excessive toxicity resulting. These patients should be treated in consultation with a pediatric oncologist. * Burkitt type leukemia * Ph+ ALL at time of diagnosis

Inclusion Criteria

Exclusion Criteria

* Newly diagnosed de novo B-precursor acute lymphoblastic leukemia (ALL) as determined by World Health Organization (WHO) criteria. Patients must have unequivocal diagnosis of precursor B ALL. This includes an institutional immunophenotyping report that is to assign B-lineage or T-lineage.
* "Ph-like" signature, as determined by low density micro-array (LDA) card
* Jak-targetable genetic signature as defined by any of the following:
* Cytokine receptor-like factor 2 (CRLF2) rearranged (JAK2 mutant or wild-type)
* JAK2 or erythropoietin receptor (EPOR) fusions.
* Other JAK pathway alterations at the discretion of the principle investigator including, but not limited to:
* SH2B adaptor protein 3 (SH2B3) deletions
* Interleukin-7 receptor subunit alpha (IL7RA) mutations
* Prior therapy
* Prior to starting ruxolitinib, patients must have completed a 4-drug induction regimen with intrathecal chemotherapy (modified aBFM regimen or equivalent) as per the institutional standard of care. Recommended induction treatment is outlined in Section 5.1.2.
* No additional prior therapy for acute leukemia except emergency therapy (corticosteroids or hydroxyurea) for blast cell crisis, superior vena cava syndrome, or renal failure due to leukemic infiltration of the kidneys. When indicated, leukapheresis or exchange transfusion is recommended to reduce the white blood cell count (WBC).
* Screening may occur at any point prior to or during induction therapy
* Age ≥ 18 years and \< 40 years. Because this is specifically a study of the adolescent and young adult population and no adverse event data are currently available on the use of this pediatric-based chemotherapy regimen in patients ≥ 40 years of age, older adults are excluded from this study, but may be eligible for future trials.
* Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Karnofsky ≥ 60%)
* Platelet count \> 25,000/uL.
* Patients must have normal organ function as defined below:
* total bilirubin ≤ 2 mg/dL
* aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 2.5 × institutional upper limit of normal
* creatinine within normal institutional limits OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
* Because the therapeutic agents used in this study are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation.
* Ability to understand and the willingness to sign a written informed consent document.

* Patients who are receiving any other investigational agent.
* Patients with a "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for ≥ 3 years.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to ruxolitinib or other agents used in study.
* Use of any potent cytochrome P450 (CYP) 3A4 inhibitor or inducer within 5 half-lives before the first dose of the study drug. Potent inhibitors of CYP3A4 include systemic ketoconazole, posaconazole, voriconazole, clarithromycin, itraconazole, nefazodone, and telithromycin. At the fluconazole dose of 200mg daily used this regimen, there is minimal inhibition of CYP3A4 \[36\] and therefore fluconazole is not prohibited on this trial and no dose modifications should be made in the presence of fluconazole.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Pregnant women are excluded from this study because ruxolitinib is a class C agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ruxolitinib breastfeeding should be discontinued if the mother is treated with ruxolitinib. These potential risks may also apply to other agents used in this study.
* Down Syndrome due to the likelihood of excessive toxicity resulting. These patients should be treated in consultation with a pediatric oncologist.
* Burkitt type leukemia
* Ph+ ALL at time of diagnosis

Contacts and Locations

Study Contact

Clinical Trials Office

CONTACT

1-855-702-8222

cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator

Wendy Stock, MD

PRINCIPAL_INVESTIGATOR

University of Chicago

Study Locations (Sites)

University of Chicago Medical Center

Chicago, Illinois, 60637

United States

Collaborators and Investigators

Sponsor: University of Chicago

Wendy Stock, MD, PRINCIPAL_INVESTIGATOR, University of Chicago

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2019-05-28

Study Completion Date2027-09-05

Study Record Updates

Study Start Date2019-05-28

Study Completion Date2027-09-05

Terms related to this study

Additional Relevant MeSH Terms

Acute Lymphoblastic Leukemia
ALL, Childhood
ALL