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

NCT03571321 | Recruiting Phase 1 FDA Drug

• 1 other identifier: IRB17-1110
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

ALL, Childhood; Acute Lymphoblastic Leukemia; ALL

Outcome Measures

Primary Outcomes (1)

• 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

  Determined by rate of side effects seen when combination is given

  24 weeks

Secondary Outcomes (3)

• Rate of participants that are minimal residual disease (MRD) negative at end of induction therapy

  4 weeks

• Overall survival rate

  2 years

• Event-free survival rate

  2 years

Study Arms (1)

Ruxolitinib

EXPERIMENTAL

Participants 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.

Drug: Ruxolitinib; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Mercaptopurine; Drug: Vincristine; Drug: Pegaspargase; Drug: Rituximab; Drug: Methotrexate (Intrathecal Administration); Drug: Methotrexate (Intravenous Administration); Drug: Dexamethasone; Drug: Doxorubicin; Drug: Thioguanine; Drug: Methotrexate Oral Product

Interventions

Ruxolitinib DRUG

Participants will receive one of 3 doses \[taken by mouth\] (30 mg, 40 mg, or 50 mg) depending on when they are enrolled to the study. Remission consolidation regimen: * Days 1-14 and 29-43 Interim maintenance regimen: * Days 1-14 and 29-43 Delayed Intensification regimen: * Days 1-14 and 29-43

Also known as: Jakafi

Ruxolitinib

Cyclophosphamide DRUG

Remission consolidation regimen: * 1000 mg/m2 by intravenous infusion (IV) on Day 1 and Day 29 Delayed Intensification regimen: * 1000 mg/m2 IV on Day 29

Ruxolitinib

Cytarabine DRUG

Remission consolidation regimen: * 75 mg/m2/day IV or subcutaneously (SC) on Days 1-4 (i.e., 4 doses), 8-11, 29-32, and 36-39 Delayed Intensification regimen: * 75 mg/m2/day IV or SC on Days 29-32 and 36-39

Ruxolitinib

Mercaptopurine DRUG

Taken by mouth. Remission consolidation regimen: * 60 mg/m2 on Days 1-14 and 29-42 Maintenance Therapy: * 75 mg/m2 on Days 1-84

Ruxolitinib

Vincristine DRUG

Remission consolidation regimen: * 1.5 mg/m2 (maximum 2 mg) IV once per week on Days 15, 22, 43, and 50 Interim maintenance regimen: * 1.5 mg/m2 (maximum 2 mg) IV on Days 1, 11, 21, 31, and 41 Delayed Intensification regimen: * 1.5 mg/m2 (maximum 2 mg) IV on Days 1, 8, 15, 43, and 50 Maintenance Therapy: * 1.5 mg/m2 (maximum 2 mg) IV on Days 1, 29, and 57

Ruxolitinib

Pegaspargase DRUG

Remission consolidation regimen: * 2500 IU/m2 given by intramuscular (IM) injection or IV on Days 15 and 43 Interim maintenance regimen: * 2500 IU/m2 IM or IV on Days 2 and 22 Delayed Intensification regimen: * 2500 IU/m2 IM or IV on Day 4 (OR Day 5 OR Day 6) AND Day 43.

Ruxolitinib

Rituximab DRUG

For patients that have cluster of differentiation antigen 20 positive (CD20+) disease only. Remission consolidation regimen: * 375 mg/m2 IV on Days 1, 8, 29 and 36 Interim maintenance regimen: * 375 mg/m2 IV on Days 1 and 11 Delayed Intensification regimen: * 375 mg/m2 IV on Days 1 and 8

Ruxolitinib

Methotrexate (Intrathecal Administration) DRUG

Drug is given through a needle which is inserted in one of the spaces between the bones in the lower back (intrathecal \[IT\] administration). Remission consolidation regimen: * 15 mg on Days 1, 8, 15, and 22 Interim maintenance regimen: * 15 mg on Days 1 and 31 Delayed Intensification regimen: * 15 mg on Days 1, 29, and 36 Maintenance Therapy: * 15 mg on Day 1 * 15 mg on Day 29 (First 4 courses only)

Ruxolitinib

Methotrexate (Intravenous Administration) DRUG

Interim maintenance regimen: * 100 mg/m2 IV on Days 1, 11, 21, 31, and 41

Ruxolitinib

Dexamethasone DRUG

Taken by mouth or given by IV infusion. Delayed Intensification regimen: * 10 mg/m2 per day (divided into 2 doses) on Days 1-7 and 15-21 Maintenance Therapy: * 6 mg/m2 per day (divided into 2 doses) on Days 1-5, 29-33, and 57-61

Ruxolitinib

Doxorubicin DRUG

Delayed Intensification regimen: * 25 mg/m2 IV on Days 1, 8, 15

Ruxolitinib

Thioguanine DRUG

Taken by mouth at least 1 hour after evening meal. Delayed Intensification regimen: * 60 mg/m2 on Days 29-42

Ruxolitinib

Methotrexate Oral Product DRUG

Taken by mouth. Maintenance Therapy: * 20 mg/m2 weekly (on Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78) * Not given on Day 29 of first 4 courses (on days when IT Methotrexate is given\]

Ruxolitinib

Eligibility Criteria

• Age: 18 Years - 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Chicago: lead
• Incyte Corporation: collaborator

Study Sites (1)

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

ruxolitinib; Cyclophosphamide; Cytarabine; Mercaptopurine; Vincristine; pegaspargase; Rituximab; Methotrexate; Administration, Intravenous; Dexamethasone; Doxorubicin; Thioguanine

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Sulfhydryl Compounds; Sulfur Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aminopterin; Pterins; Pteridines; Drug Administration Routes; Drug Therapy; Therapeutics; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Wendy Stock, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trials Office

CONTACT

1-855-702-8222; cancerclinicaltrials@bsd.uchicago.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2018
• First Posted: June 27, 2018
• Study Start: May 28, 2019
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 5, 2027
• Last Updated: January 9, 2026

Record last verified: 2026-01

Locations

US (1)