Ruxolitinib Phosphate or Dasatinib With Chemotherapy in Treating Patients With Relapsed or Refractory Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia

NCT ID: NCT02420717

Last Updated: 2025-06-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-15
• Study Completion Date: 2021-01-20

Brief Summary

This phase II trial studies the side effects and best dose of ruxolitinib phosphate and how well it works compared to dasatinib when given with chemotherapy in treating patients with Philadelphia chromosome-like acute lymphoblastic leukemia that has come back (relapsed) or has not responded to treatment (refractory). Ruxolitinib phosphate and dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving ruxolitinib phosphate or dasatinib with chemotherapy works better in treating patients with previously treated acute lymphoblastic leukemia.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the safety and maximal tolerated dose (MTD) of ruxolitinib phosphate (ruxolitinib) in combination with chemotherapy in patients with Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL). (Phase I, ruxolitinib cohort only) II. To determine the response rate (complete response [CR]/CR with incomplete marrow recovery [CRi]) of ruxolitinib or dasatinib in combination with chemotherapy in patients with Ph-like ALL. (Phase II)

SECONDARY OBJECTIVES:

I. To determine the response rate (CR/CRi) of ruxolitinib in combination with chemotherapy in patients with Ph-like ALL. (Phase I, ruxolitinib cohort only) II. To determine the duration of response, disease-free survival and overall survival of ruxolitinib in combination with chemotherapy in patients with Ph-like ALL. (Phase I, ruxolitinib cohort only) III. To determine the safety and toxicity profile of ruxolitinib or dasatinib in combination with chemotherapy in patients with Ph-like ALL. (Phase II) IV. To determine the duration of response, disease-free survival and overall survival of ruxolitinib or dasatinib in combination with chemotherapy in patients with Ph-like ALL. (Phase II)

OUTLINE: This is a phase I, dose escalation study of ruxolitinib followed by a phase II study. Patients are assigned to 1 of 2 cohorts.

COHORT A: Patients receive ruxolitinib phosphate orally (PO) twice daily (BID). Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

COHORT B: Patients receive dasatinib PO once daily (QD). Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

INTENSIVE CHEMOTHERAPY: After cycle 1, patients not achieving a response also receive cyclophosphamide intravenously (IV) over 3 hours BID on days 1-3, doxorubicin IV over 24-48 hours on day 4, vincristine IV over 30 minutes on days 4 and 11, and dexamethasone PO QD or IV over 30 minutes on days 1-4 and 11-14 of cycles 1, 3, 5, and 7. Patients receive methotrexate IV over 24 hours on day 1, leucovorin IV over 1 hour or PO every 6 hours on days 2-5, cytarabine IV over 2 hours BID on days on days 2 and 3 of cycles 2, 4, 6, and 8. At the discretion of the treating physician, patients may also receive rituximab IV over several hours on days 1 and 11 of cycles 1 and 3 and on days 1 and 8 of cycles 2 and 4 only. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive mercaptopurine PO thrice daily (TID), methotrexate PO once a week, vincristine IV over 30 minutes on day 1, and prednisone PO on days 1-5. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days.

Conditions

Recurrent B Acute Lymphoblastic Leukemia; Recurrent Ph-Like Acute Lymphoblastic Leukemia; Refractory B Acute Lymphoblastic Leukemia; Refractory Ph-Like Acute Lymphoblastic Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A (ruxolitinib phosphate)

Patients receive ruxolitinib phosphate PO BID. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

Given IV

Cytarabine

Intervention Type: DRUG

Given IV

Dexamethasone

Intervention Type: DRUG

Given PO or IV

Doxorubicin

Intervention Type: DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Leucovorin

Intervention Type: DRUG

Given IV or PO

Mercaptopurine

Intervention Type: DRUG

Given PO

Methotrexate

Intervention Type: DRUG

Given IV and PO

Prednisone

Intervention Type: DRUG

Given PO

Rituximab

Intervention Type: BIOLOGICAL

Given IV

Ruxolitinib Phosphate

Intervention Type: DRUG

Given PO

Vincristine

Intervention Type: DRUG

Given IV

Cohort B (dasatinib)

Patients receive dasatinib PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

Given IV

Cytarabine

Intervention Type: DRUG

Given IV

Dasatinib

Intervention Type: DRUG

Given PO

Dexamethasone

Intervention Type: DRUG

Given PO or IV

Doxorubicin

Intervention Type: DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Leucovorin

Intervention Type: DRUG

Given IV or PO

Mercaptopurine

Intervention Type: DRUG

Given PO

Methotrexate

Intervention Type: DRUG

Given IV and PO

Prednisone

Intervention Type: DRUG

Given PO

Rituximab

Intervention Type: BIOLOGICAL

Given IV

Vincristine

Intervention Type: DRUG

Given IV

Phase 1

Patients Receive ruxolitinib Phosphate PO BID. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

Given IV

Cytarabine

Intervention Type: DRUG

Given IV

Dexamethasone

Intervention Type: DRUG

Given PO or IV

Doxorubicin

Intervention Type: DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Leucovorin

Intervention Type: DRUG

Given IV or PO

Mercaptopurine

Intervention Type: DRUG

Given PO

Methotrexate

Intervention Type: DRUG

Given IV and PO

Prednisone

Intervention Type: DRUG

Given PO

Rituximab

Intervention Type: BIOLOGICAL

Given IV

Ruxolitinib Phosphate

Intervention Type: DRUG

Given PO

Vincristine

Intervention Type: DRUG

Given IV

Interventions

Cyclophosphamide

Given IV

Intervention Type: DRUG

Cytarabine

Given IV

Intervention Type: DRUG

Dasatinib

Given PO

Intervention Type: DRUG

Dexamethasone

Given PO or IV

Intervention Type: DRUG

Doxorubicin

Given IV

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Leucovorin

Given IV or PO

Intervention Type: DRUG

Mercaptopurine

Given PO

Intervention Type: DRUG

Methotrexate

Given IV and PO

Intervention Type: DRUG

Prednisone

Given PO

Intervention Type: DRUG

Rituximab

Given IV

Intervention Type: BIOLOGICAL

Ruxolitinib Phosphate

Given PO

Intervention Type: DRUG

Vincristine

Given IV

Intervention Type: DRUG

Other Intervention Names

(-)-Cyclophosphamide; 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate; Carloxan; Ciclofosfamida; Ciclofosfamide; Cicloxal; Clafen; Claphene; CP monohydrate; CTX; CYCLO-cell; Cycloblastin; Cycloblastine; Cyclophospham; Cyclophosphamid monohydrate; Cyclophosphamide Monohydrate; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Cytoxan; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; Neosar; Revimmune; Syklofosfamid; WR- 138719; .beta.-Cytosine arabinoside; 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-.beta.-D-Arabinofuranosylcytosine; 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-Beta-D-arabinofuranosylcytosine; 1.beta.-D-Arabinofuranosylcytosine; 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-; 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-; Alexan; Ara-C; ARA-cell; Arabine; Arabinofuranosylcytosine; Arabinosylcytosine; Aracytidine; Aracytin; Aracytine; Beta-Cytosine Arabinoside; CHX-3311; Cytarabinum; Cytarbel; Cytosar; Cytosine Arabinoside; Cytosine-.beta.-arabinoside; Cytosine-beta-arabinoside; Erpalfa; Starasid; Tarabine PFS; U 19920; U-19920; Udicil; WR-28453; BMS-354825; Dasatinib Hydrate; Dasatinib Monohydrate; Sprycel; Aacidexam; Adexone; Aknichthol Dexa; Alba-Dex; Alin; Alin Depot; Alin Oftalmico; Amplidermis; Anemul mono; Auricularum; Auxiloson; Baycadron; Baycuten; Baycuten N; Cortidexason; Cortisumman; Decacort; Decadrol; Decadron; Decadron DP; Decalix; Decameth; Decasone R.p.; Dectancyl; Dekacort; Deltafluorene; Deronil; Desamethasone; Desameton; Dexa-Mamallet; Dexa-Rhinosan; Dexa-Scheroson; Dexa-sine; Dexacortal; Dexacortin; Dexafarma; Dexafluorene; Dexalocal; Dexamecortin; Dexameth; Dexamethasone Intensol; Dexamethasonum; Dexamonozon; Dexapos; Dexinoral; Dexone; Dinormon; Fluorodelta; Fortecortin; Gammacorten; Hexadecadrol; Hexadrol; Lokalison-F; Loverine; Methylfluorprednisolone; Millicorten; Mymethasone; Orgadrone; Spersadex; TaperDex; Visumetazone; ZoDex; Adriablastin; Hydroxydaunomycin; Hydroxyl Daunorubicin; Hydroxyldaunorubicin; Folinic acid; 3H-Purine-6-thiol; 6 MP; 6 Thiohypoxanthine; 6 Thiopurine; 6-Mercaptopurine; 6-Mercaptopurine Monohydrate; 6-MP; 6-Purinethiol; 6-Thiopurine; 6-Thioxopurine; 6H-Purine-6-thione, 1,7-dihydro- (9CI); 7-Mercapto-1,3,4,6-tetrazaindene; Alti-Mercaptopurine; Azathiopurine; Bw 57-323H; Flocofil; Ismipur; Leukerin; Leupurin; Mercaleukim; Mercaleukin; Mercaptina; Mercaptopurinum; Mercapurin; Mern; NCI-C04886; Puri-Nethol; Purimethol; Purine, 6-mercapto-; Purine-6-thiol (8CI); Purine-6-thiol, monohydrate; Purinethiol; Purinethol; U-4748; WR-2785; Abitrexate; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex; Folex PFS; Lantarel; Ledertrexate; Lumexon; Maxtrex; Medsatrexate; Metex; Methoblastin; Methotrexate LPF; Methotrexate Methylaminopterin; Methotrexatum; Metotrexato; Metrotex; Mexate; Mexate-AQ; MTX; Novatrex; Rheumatrex; Texate; Tremetex; Trexeron; Trixilem; WR-19039; .delta.1-Cortisone; 1, 2-Dehydrocortisone; Adasone; Cortancyl; Dacortin; DeCortin; Decortisyl; Decorton; Delta 1-Cortisone; Delta-Dome; Deltacortene; Deltacortisone; Deltadehydrocortisone; Deltasone; Deltison; Deltra; Econosone; Lisacort; Meprosona-F; Metacortandracin; Meticorten; Ofisolona; Orasone; Panafcort; Panasol-S; Paracort; Perrigo Prednisone; PRED; Predicor; Predicorten; Prednicen-M; Prednicort; Prednidib; Prednilonga; Predniment; Prednisone Intensol; Prednisonum; Prednitone; Promifen; Rayos; Servisone; SK-Prednisone; ABP 798; BI 695500; C2B8 Monoclonal Antibody; Chimeric Anti-CD20 Antibody; CT-P10; IDEC-102; IDEC-C2B8; IDEC-C2B8 Monoclonal Antibody; MabThera; Monoclonal Antibody IDEC-C2B8; PF-05280586; Rituxan; Rituximab ABBS; Rituximab Biosimilar ABP 798; Rituximab Biosimilar BI 695500; Rituximab Biosimilar CT-P10; Rituximab Biosimilar GB241; Rituximab Biosimilar IBI301; Rituximab Biosimilar JHL1101; Rituximab Biosimilar PF-05280586; Rituximab Biosimilar RTXM83; Rituximab Biosimilar SAIT101; rituximab biosimilar TQB2303; rituximab-abbs; RTXM83; Truxima; INCB-18424 Phosphate; Jakafi; Leurocristine; VCR; Vincrystine

Eligibility Criteria

Inclusion Criteria

• Patients with previously treated B-cell ALL (relapsed and/or refractory after prior therapy)
• Bone marrow involvement with >= 5% lymphoblasts
• Documented genetic lesion(s) known to confer susceptibility to inhibition by either ruxolitinib or dasatinib or cytokine receptor-like factor 2 (CRLF2) positivity by flow cytometry (for the ruxolitinib cohort)
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Total bilirubin < 2.0 mg/dL
• Serum glutamate pyruvate transaminase (SGPT) or serum glutamic oxaloacetic transaminase (SGOT) < 3 x upper limit of normal (ULN)
• Creatinine < 2 mg/dL
• Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (beta-hCG) pregnancy test result within 14 days prior to the first dose of study drugs and must agree to use an effective contraception method during the study and for 30 days following the last dose of study drug; females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy; appropriate methods of birth control include the following: any 2 of the following methods used together: birth control implants, injections, or pills (except for progesterone only pills), intrauterine device (IUD), vasectomy, tubal ligation, barrier method (female or male condom with spermicide, cervical cap with spermicide, diaphragm with spermicide); male condom with spermicide and diaphragm; male condom with spermicide and cervical cap; unacceptable methods of birth control include using no birth control, withdrawal, rhythm method, vaginal sponge, any barrier method that does not use spermicide, progesterone only pills, and using male and female condoms at the same time
• Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 30 days following the last dose of study drug
• Patients or their legally authorized representative must provide written informed consent

Exclusion Criteria

• Burkitt's leukemia or lymphoma, T-cell ALL or lymphoblastic lymphoma
• Patients having undergone prior allogeneic stem cell transplant within 3 months or having active graft versus host disease
• Patient is pregnant or breastfeeding
• Patients with uncontrolled active infections (fever >= 38 degrees Celsius [C], septic shock)
• Isolated extramedullary relapse (i.e. testicular, central nervous system)
• Current or chronic hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV)
• Concurrent chemotherapy (except intrathecal chemotherapy)
• Major surgery within 4 weeks prior to first study dose
• Systemic chemotherapy/radiotherapy/investigational therapy within 14 days (with the exception of hydroxyurea and steroids) prior to starting therapy; for patients receiving ALL maintenance with 6-mercaptopurine, methotrexate, vincristine, and steroids - these agents should be discontinued at least 48 hours prior to start of study drugs; for patients on oral targeted therapies (such as imatinib, dasatinib, ponatinib), - these agents should be discontinued at least 48 hours prior to start of study drugs
• Patients must have recovered from acute non hematologic toxicity (to =< grade 1) of all previous therapy prior to enrollment
• Known active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF), use of CNS-directed local treatment for active disease within the prior 28 days, symptomatic CNS leukemia (i.e., cranial nerve palsies or other significant neurologic dysfunction) within 28 days; patients may have history of CNS leukemic involvement if definitively treated with prior therapy and no evidence of active disease (defined as >= 2 consecutive spinal fluid assessments with no evidence of disease) at the time of registration; prophylactic intrathecal chemotherapy is not a criterion for exclusion
• Patients with active heart disease (New York Heart Association [NYHA] class 3-4 as assessed by history and physical examination, unstable angina/stroke/myocardial infarction within the last 6 months)
• Patients with a cardiac ejection fraction (as measured by either multi-gated acquisition [MUGA] scan or echocardiogram) < 40%; (Note: patients who have had prior anthracycline exposure of > 250 mg/m^2 may be eligible after discussion with the principal investigator [PI])
• Second malignancy other than basal cell or squamous cell carcinoma of the skin or in situ carcinoma of the cervix or the breast, unless they are successfully treated with curative intent for more than 2 years before entering the study
• Malabsorption syndrome or other conditions that preclude enteral route of administration
• Patients requiring strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study

• Minimum Eligible Age: 10 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nitin Jain

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

M D Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.mdanderson.org

University of Texas MD Anderson Cancer Center Website

Other Identifiers

NCI-2015-00779

Identifier Type: REGISTRY

Identifier Source: secondary_id

2014-0521

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA016672

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2014-0521

Identifier Type: -

Identifier Source: org_study_id