- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02420717
Ruxolitinib Phosphate or Dasatinib With Chemotherapy in Treating Patients With Relapsed or Refractory Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia
A Phase I-II Study of the Combination of Ruxolitinib or Dasatinib With Chemotherapy in Patients With Philadelphia Chromosome (Ph)-Like Acute Lymphoblastic Leukemia (ALL)
Study Overview
Status
Conditions
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Texas
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Houston, Texas, United States, 77030
- M D Anderson Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cohort A (ruxolitinib phosphate)
Patients receive ruxolitinib phosphate PO BID.
Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
Correlative studies
Given IV
Other Names:
Given IV
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Given PO
Other Names:
Given PO
Other Names:
Given PO or IV
Other Names:
Given IV
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Given IV
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Given IV
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Given PO
Other Names:
Given IV or PO
Other Names:
Given IV and PO
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Experimental: Cohort B (dasatinib)
Patients receive dasatinib PO QD.
Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
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Correlative studies
Given IV
Other Names:
Given PO
Other Names:
Given IV
Other Names:
Given PO
Other Names:
Given PO
Other Names:
Given PO or IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV or PO
Other Names:
Given IV and PO
Other Names:
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Experimental: Phase 1
Patients Receive ruxolitinib Phosphate PO BID.
Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
|
Correlative studies
Given IV
Other Names:
Given IV
Other Names:
Given PO
Other Names:
Given PO
Other Names:
Given PO or IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given PO
Other Names:
Given IV or PO
Other Names:
Given IV and PO
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximal Tolerated Dose (MTD) of Ruxolitinib in Combination With Chemotherapy Defined as the Highest Dose Level at Which no More Than 1 Out of 6 Patients Experience a Dose Limiting Toxicity (Phase I)
Time Frame: 42 days
|
The method of Thall, Simon and Estey will be used for toxicity monitoring for this study.
The severity of the toxicities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 whenever possible.
Safety data will be summarized by category, severity and frequency.
|
42 days
|
Participants With Complete Response (Complete Response [CR]/CR With Incomplete Marrow Recovery [CRi]) (Phase II)
Time Frame: 42 days
|
Complete Response (CR) is disappearance of all clinical and/or radiologic evidence of disease, Neutrophil count ≥ 1.0 x 10^9/L, Platelet count ≥ 100 x 10^9/L, Normal bone marrow differential (≤ 5% blasts), No extra-medullary leukemia.
Complete Remission with Incomplete Blood Count Recovery (CRi) is CR except for ANC < 1.0 x 10^9/L and/or platelets < 100 x 10^9/L.
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42 days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival
Time Frame: Up to 4 years 7 months
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Time from date of treatment start until date of death due to any cause or last Follow-up.
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Up to 4 years 7 months
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Progression-free Survival
Time Frame: Up to 4 years 7 months
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Time from date of treatment start until the date of first objective documentation of disease-relapse.
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Up to 4 years 7 months
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Nitin Jain, M.D. Anderson Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Disease Attributes
- Chromosome Aberrations
- Translocation, Genetic
- Leukemia
- Recurrence
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Leukemia, Lymphoid
- Philadelphia Chromosome
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Autonomic Agents
- Peripheral Nervous System Agents
- Antiviral Agents
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Protease Inhibitors
- Protective Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Dermatologic Agents
- Micronutrients
- Protein Kinase Inhibitors
- Antibiotics, Antineoplastic
- Vitamins
- Reproductive Control Agents
- Antidotes
- Vitamin B Complex
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Dexamethasone
- Dexamethasone acetate
- BB 1101
- Cyclophosphamide
- Antibodies
- Immunoglobulins
- Rituximab
- Leucovorin
- Prednisone
- Doxorubicin
- Liposomal doxorubicin
- Antibodies, Monoclonal
- Antineoplastic Agents, Immunological
- Cytarabine
- Methotrexate
- Vincristine
- Daunorubicin
- Mercaptopurine
- Cortisone
- Dasatinib
Other Study ID Numbers
- 2014-0521 (Other Identifier: M D Anderson Cancer Center)
- P30CA016672 (U.S. NIH Grant/Contract)
- NCI-2015-00779 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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