Accelerated Phase of DiseasePhase 1/2NCT02210858
Tipifarnib in Treating Patients With Chronic Myeloid Leukemia, Chronic Myelomonocytic Leukemia, or Undifferentiated Myeloproliferative Disorders
A Phase 1/2 study testing Laboratory Biomarker Analysis and Tipifarnib in people with Accelerated Phase of Disease and Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative, run by National Cancer Institute (NCI) at 2 sites in United States.
Trial summary
This phase 1-2 trial studies the side effects and how well tipifarnib works in treating patients with chronic myeloid leukemia, chronic myelomonocytic leukemia, or undifferentiated myeloproliferative disorders. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 21 years and olderHealthy volunteers can take part
- Conditions the study is for
- Accelerated Phase of Disease, Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative, Chronic Myelogenous Leukemia, BCR-ABL1 Positive
- What is being tested?
- Laboratory Biomarker Analysis and Tipifarnib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2000to Mar 2017
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patients with a diagnosis (> 3 months prior to enrollment) of:
- Chronic myeloid leukemia (CML) (Philadelphia chromosome positive or polymerase chain reaction [PCR] positive for breakpoint cluster region [BCR]-Abelson murine leukemia viral oncogene homolog 1 [ABL]) in chronic phase with:
- Persistent or progressive disease on maximum tolerated interferon therapy, or STI571 (if eligible and able to receive this drug), as evidenced by increasing white blood cell (WBC) count, peripheral blood myeloid immaturity and/or progressive anemia, and/or persistence or relapse of abnormal cytogenetic and/or molecular findings
- Interferon or STI571 intolerant
- CML (Philadelphia chromosome positive or PCR positive for BCR-ABL) in accelerated phase (< 20% blasts in the peripheral blood and bone marrow) with persistent or progressive disease on STI571 (if eligible and able to receive this drug)
- CML patients are eligible if they have not received interferon or STI571 because they are allergic to these drugs or refuse their use
Show all 19Show fewer
- Chronic myelomonocytic leukemia (CMML)
- Proliferative-type (WBC > 12,000/mL)
- Less than 5% blasts in the peripheral blood and < 20% blasts in the bone marrow
- Undifferentiated myeloproliferative disorder (UMPD)
- Atypical (i.e. Philadelphia chromosome-negative) CML
- Four weeks must have elapsed since the use of any previous pharmacotherapy including interferon, hematopoietic growth factors, and cytotoxic chemotherapy (6 weeks for prior mitomycin or nitrosoureas); hydroxyurea may be used to manage elevated cell counts in patients up to the time they begin investigational therapy
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- Patients are capable of swallowing capsules
- Total bilirubin is > 1.5 X the upper limit of normal (ULN) where the analysis is performed; for example, for Stanford University Hospital, the ULN for total bilirubin is 1.3
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) are > 2 X the ULN; for example, for Stanford University Hospital, the ULN for ALT is 35, and the ULN for AST is 41
- Serum creatinine of < 2.0
- Life expectancy > 4 months
- Written inform consent must be obtained
Who cannot join
- Blast crisis phase of CML and atypical CML/ undifferentiated myeloproliferative disorders
- Patients with > 20% blasts in the peripheral blood or bone marrow are excluded
- Prior allogeneic bone marrow transplantation
- Patients with severe disease other than CML, CMML, or UMPD which is expected to prevent compliance with the protocol
- Patients with septicemia or other severe infections
- Pregnant or breast-feeding females
Show all 12Show fewer
- Women of reproductive age should use contraception while on study
- Patients may not receive androgens during the study
- Requirement for ongoing therapy with corticosteroids (> 10 mg/d prednisone or equivalent steroid dosage) other than as pre-medication for transfusions
- Patients with iron deficiency; if a marrow aspirate is not available, transferrin saturation must be > 20% and serum ferritin > 50 ng/mL; this exclusion criterion will be removed if the iron deficiency state is corrected before enrollment
- Patients with other contributing causes of anemia such as autoimmune or hereditary hemolytic disorders, gastrointestinal (GI) blood loss, B12 or folate deficiency, or hypothyroidism; patients who require platelet transfusions, or have thrombocytopenia-related bleeding
- Inability to return for follow-up visits/studies to assess toxicity and response to therapy
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Stanford Cancer Institute
Palo Alto, California, 94304
University of Rochester
Rochester, New York, 14642
About this study
Official title: Phase I/II Study of Tipifarnib [Zarnestra, Farnesyltransferase Inhibitor R115777 (NSC 702818)] in Patients With Myeloproliferative Disorders
This phase 1-2 trial studies the side effects and how well tipifarnib works in treating patients with chronic myeloid leukemia, chronic myelomonocytic leukemia, or undifferentiated myeloproliferative disorders. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
PRIMARY OBJECTIVES:
- To describe the toxicities of R115777 (tipifarnib) in adult patients with myeloproliferative disorders.
- To assess hematologic responses, including changes in white blood cell count and erythroid responses.
SECONDARY OBJECTIVES:
- To assess bone marrow cytogenetic responses to R115777.
- To analyze for the presence of neuroblastoma (N)/Kirsten rat sarcoma viral oncogene homolog (K-Ras) mutations in patient bone marrow samples.
- To analyze the effect of R115777 on Ras /DnaJ (Hsp40) homolog, subfamily A, member 1(HDJ-2) farnesylation in patient bone marrow/peripheral blood mononuclear cells.
- To analyze the effect of R115777 on mitogen-activated protein (MAP) kinase activation in patient bone marrow mononuclear cells.
- To perform colony forming unit granulocyte-macrophage (CFU-GM) cytotoxicity assays using patients' hematopoietic cells with R115777.
OUTLINE:
Patients receive tipifarnib orally (PO) twice daily (BID) on days 1-21. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a good hematologic response may continue treatment at the discretion of the treating physician.
- Conditions
- Accelerated Phase of Disease, Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative, Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Chronic Myelomonocytic Leukemia, Chronic Phase of Disease, Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
- Being tested
- Laboratory Biomarker Analysis, Tipifarnib
- Medical subject headings
- Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Myelomonocytic, Chronic, Myeloproliferative Disorders, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
TipifarnibDrug
Also called R115777, Zarnestra
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (tipifarnib) | Experimental | Patients receive tipifarnib PO BID on days 1-21. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Receives: Other: Laboratory Biomarker Analysis; Drug: Tipifarnib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Erythroid response in non-transfusion dependent patients
Major response is defined as a > 2.0 g/dL rise in the hemoglobin after 2 to 4 cycles of therapy. Minor response is defined as a > 1.0 to < 2.0 g/dL rise in the hemoglobin after 2 to 4 cycles of therapy.
Measured: Up to 16 weeks
Erythroid response in transfusion-dependent patients
Major response is defined as transfusion-independent after 2 to 4 cycles of therapy or a > 2.0 g/dL rise in hemoglobin without transfusion. Minor response is defined as > 1 to < 2.0 g/dL incremental rise in hemoglobin with a decrease in transfusion requirements of at least 50% compared to the mean transfusion requirement during the 8-week pre-study period.
Measured: Up to 16 weeks
Incidence of adverse events related to tipifarnib assessed by National Cancer Institute Common Toxicity version 2.0
Measured: Up to 16 weeks
WBC response (complete response, defined as normalization of WBC count in patients with an elevated WBC count prior to treatment and partial response, defined as > 50% reduction in WBC count without normalization of WBC count)
For all hematologic responses, the duration of response must be at least 2 months.
Measured: Up to 16 weeks
Secondary outcomes (2)
Cytogenetic response (including Philadelphia chromosome-positive cells in metaphases in CML)
Measured: Up to 16 weeks
In vitro correlative studies (including N/K-Ras mutation analysis, N/K-Ras/HDJ-2 farnesylation, MAP kinase activation, and bone marrow CFU-GM cytotoxicity assays using tipifarnib with patients' hematopoietic cells)
Measured: Up to week 3 (course 4)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2014 (estimated)
- Study startMay 2000
- Primary completion12 Nov 2004
- Study completionMar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Accelerated Phase of DiseaseStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Peter Greenberg, Principal investigator, Stanford Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02210858
- Sponsor's protocol ID
- NCI-2014-01606
- Other IDs
- NCI-2014-01606, SUMC-NCI-38, NCI-38, CDR0000067864, CTEP 38, 38, P30CA124435, IRB-13343
- Status last verified
- May 2018
- First submitted
- 5 Aug 2014
- Last updated
- 4 Jun 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No