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
- Are there results?
- None posted in the registry
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
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- 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
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- 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
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Tipifarnib [Zarnestra, Farnesyltransferase Inhibitor R115777 (NSC 702818)] in Patients With Myeloproliferative Disorders
- ClinicalTrials.gov ID
- NCT02210858
- Acronym / sponsor ID
- NCI-2014-01606
- 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
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- May 2000 (actual)
- Primary completion
- 12 Nov 2004 (actual)
- Study completion
- Mar 2017 (actual)
- First posted
- 7 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (tipifarnib) | Experimental | Other: Laboratory Biomarker Analysis, Drug: TipifarnibPatients 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. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Patients with a diagnosis (> 3 months prior to enrollment) of:
- Chronic myelomonocytic leukemia (CMML)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (tipifarnib) |
| TipifarnibAlso: R115777, ZarnestraGiven PO | Drug | Treatment (tipifarnib) |
Primary outcome
Erythroid response in non-transfusion dependent patients
Time frame: Up to 16 weeks
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.
Erythroid response in transfusion-dependent patients
Time frame: Up to 16 weeks
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.
Incidence of adverse events related to tipifarnib assessed by National Cancer Institute Common Toxicity version 2.0
Time frame: 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)
Time frame: Up to 16 weeks
For all hematologic responses, the duration of response must be at least 2 months.
2 secondary outcomes
Cytogenetic response (including Philadelphia chromosome-positive cells in metaphases in CML)
Time frame: 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)
Time frame: Up to week 3 (course 4)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Greenberg principal investigator
Stanford Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
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.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Erythroid response in non-transfusion dependent patients (time frame: Up to 16 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2018.