Clinical Trials /

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

NCT03571321

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).

Related Conditions:
  • B-Cell Acute Lymphoblastic Leukemia
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Ruxolitinib and Chemotherapy in Adolescents and Young Adults With Ph-like Acute Lymphoblastic Leukemia
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: IRB17-1110
  • NCT ID: NCT03571321

Conditions

  • Acute Lymphoblastic Leukemia
  • ALL, Childhood
  • ALL

Interventions

DrugSynonymsArms
RuxolitinibJakafiRuxolitinib
CyclophosphamideRuxolitinib
CytarabineRuxolitinib
MercaptopurineRuxolitinib
VincristineRuxolitinib
PegaspargaseRuxolitinib
RituximabRuxolitinib
Methotrexate (Intrathecal Administration)Ruxolitinib
Methotrexate (Intravenous Administration)Ruxolitinib
DexamethasoneRuxolitinib
DoxorubicinRuxolitinib
ThioguanineRuxolitinib
Methotrexate Oral ProductRuxolitinib

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
RuxolitinibExperimentalParticipants will receive ruxolitinib in addition to standard chemotherapy. Standard Chemotherapy Consists of: Remission consolidation therapy (lasting 8 weeks) Interim Maintenance (lasting 8 weeks) Delayed Intensification (lasting 8 weeks Maintenance Therapy (12 week courses/84 day cycles lasting 2-3 years) Prior to study entry, patients must have completed a 4-drug induction therapy regimen with intrathecal chemotherapy (modified Berlin-Frankfurt-Münster (aBFM) regimen or equivalent) as per the institution standard of care.
  • Ruxolitinib
  • Cyclophosphamide
  • Cytarabine
  • Mercaptopurine
  • Vincristine
  • Pegaspargase
  • Rituximab
  • Methotrexate (Intrathecal Administration)
  • Methotrexate (Intravenous Administration)
  • Dexamethasone
  • Doxorubicin
  • Thioguanine
  • Methotrexate Oral Product

Eligibility Criteria

        Inclusion 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.

        Exclusion Criteria:

          -  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.

        Because the lists of these agents are constantly changing, it is important to regularly
        consult a frequently-updated list such as
        http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as the
        Physicians' Desk Reference may also provide this information. As part of the
        enrollment/informed consent procedures, the patient will be counseled on the risk of
        interactions with other agents, and what to do if new medications need to be prescribed or
        if the patient is considering a new over-the-counter medicine or herbal product.

          -  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
      
Maximum Eligible Age:39 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Feasibility of adding ruxolitinib to a standard-of-care pediatric-based chemotherapy regimen in adolescents and young adult patients as determined by rate of side effects seen when combination is given
Time Frame:24 weeks
Safety Issue:
Description:Determined by rate of side effects seen when combination is given

Secondary Outcome Measures

Measure:Rate of participants that are minimal residual disease (MRD) negative at end of induction therapy
Time Frame:4 weeks
Safety Issue:
Description:
Measure:Overall survival rate
Time Frame:2 years
Safety Issue:
Description:
Measure:Event-free survival rate
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Chicago

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