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Leukemia, Myelomonocytic, ChronicPhase 2CMML/AMLNCT02807272

Tipifarnib in Subjects With Chronic Myelomonocytic Leukemia, Other MDS/MPN, and Acute Myeloid Leukemia

A Phase 2 study testing Tipifarnib in people with Leukemia, Myelomonocytic, Chronic, run by Kura Oncology, Inc. at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

A Phase 2 study to investigate the antitumor activity in terms of overall response rate (ORR) of tipifarnib in approximately 36 eligible subjects with Myelodysplastic/Myeloproliferative Neoplasias (MDS/MPN), including Chronic Myelomonocytic Leukemia (CMML), and 36 eligible subjects with Acute Myeloid Leukemia (AML). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Leukemia, Myelomonocytic, Chronic
What is being tested?
Tipifarnib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
8 sitesUnited States
Study dates
10 Jan 2017to 30 Nov 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subject is at least 18 years of age.
  • For subjects to be enrolled in the CMML or MDS/MPN cohorts:
  • Diagnosis of CMML or MDS/MPN as defined by the World Health Organization (WHO) criteria (2008).
  • For subjects enrolled in the AML cohort:
  • Documented pathological evidence of AML, as defined by WHO criteria (2008)
  • Refractory to previous induction chemotherapy, relapsed disease, or age ≥ 60 and not appropriate for standard cytotoxic therapy due to age, performance status, and/or adverse risk factors according to the treating physician
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  • Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.
  • Subject is willing and able to comply with scheduled visits, treatment plans, laboratory tests and other procedures (including bone marrow assessments).
  • At least 1 week since the last systemic therapy regimen prior to Cycle 1 Day 1. Subjects on a stable dose of hydroxyurea for at least 2 weeks prior to Cycle 1 Day 1 may continue on hydroxyurea until Cycle 1 Day 14. Subjects must have recovered to NCI CTCAE v. 4.03 < Grade 2 from all acute toxicities (excluding Grade 2 toxicities that are not considered a safety risk by the Sponsor and Investigator) or toxicity must be deemed irreversible by the Investigator.
  • Acceptable liver function:
  • Total bilirubin ≤ upper limit of normal (ULN).
  • AST (SGOT) and ALT (SGPT) ≤ 1.5 x ULN.
  • Acceptable renal function with serum creatinine ≤ 1.5 x ULN or a calculated creatinine clearance ≥ 60 mL/min using the Cockcroft-Gault or Modification of Diet in Renal Disease formulas.
  • Female subjects must be:
  • Of non-child-bearing potential (surgically sterilized or at least 2 years post-menopausal); or
  • If of child-bearing potential, subject must use a highly effective method of contraception, such as combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner or sexual abstinence. Both females and male subjects with female partners of child-bearing potential must agree to use a highly effective method of contraception for 2 weeks prior to screening, during, and at least 28 days after last dose of trial medication for females and 90 days for males. Female subjects must have a negative serum or urine pregnancy test within 72 hours prior to start of trial medication.
  • And, not breast feeding at any time during the study.
  • Written and voluntary informed consent understood, signed and dated.

Who cannot join

  • Neoplasia harbours RAS mutation (NRAS mutant, KRAS mutant or double mutant)
  • Acute promyelocytic leukemia or Bcr-Abl positive leukemia (chronic myelogenous leukemia in blast crisis)
  • Clinically active CNS leukemia
  • CMML with t(5;12) that have not yet received imatinib.
  • Participation in any interventional study within 1 week of randomization or 5 half-lives of the prior treatment agent (whichever is longer).
  • Ongoing treatment with an anticancer agent for CMML, MDS/MPN or AML not contemplated in this protocol. Subjects on a stable dose of hydroxyurea for at least 2 weeks prior to Cycle 1 Day 1 may continue on hydroxyurea until Cycle 1 Day 14.
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  • Hematopoietic stem cell transplantation (HSCT) performed within 3 months prior to Cycle 1 Day 1.
  • Concurrent use of granulocyte macrophage colony-stimulating factor (GM-CSF).
  • Prior treatment (at least 1 full treatment cycle) with a farnesyltransferase inhibitor.
  • Active coronary artery disease requiring treatment, myocardial infarction within the prior year, New York Heart Association grade III or greater congestive heart failure, cerebro-vascular attack within the prior year, or current serious cardiac arrhythmia requiring medication except atrial fibrillation.
  • Major surgery, other than diagnostic surgery, within 2 weeks prior to Cycle 1 Day 1, without complete recovery.
  • Active, concurrent malignancy requiring radiation, chemotherapy, or immunotherapy (excluding non-melanoma skin cancer, adjuvant hormonal therapy for breast cancer and hormonal treatment for castration sensitive prostate cancer).
  • Active and uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy. Known infection with human immunodeficiency virus (HIV), or an active infection with hepatitis B or hepatitis C.
  • Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study.
  • The subject has legal incapacity or limited legal capacity.
  • Significantly altered mental status that would limit the understanding or rendering of informed consent and compliance with the requirements of this protocol. Unwillingness or inability to comply with the study protocol for any reason.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Johns Hopkins University

    Baltimore, Maryland, 21231

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Mayo Clinic Florida

    Jacksonville, Florida, 32224

  • Weill Cornell Medicine

    New York, New York, 10065

  • University of Pennsylvania Hospital

    Philadelphia, Pennsylvania, 19104

  • Mayo Clinic Rochester

    Rochester, Minnesota, 55905

  • Mayo Clinic Arizona

    Scottsdale, Arizona, 85054

  • H. Lee Moffitt Cancer Center & Research Institute, Inc.

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: A Phase 2 Study of Tipifarnib in Subjects With Chronic Myelomonocytic Leukemia, Other Myelodysplastic /Myeloproliferative Neoplasias, and Acute Myeloid Leukemia

A Phase 2 study to investigate the antitumor activity in terms of overall response rate (ORR) of tipifarnib in approximately 36 eligible subjects with Myelodysplastic/Myeloproliferative Neoplasias (MDS/MPN), including Chronic Myelomonocytic Leukemia (CMML), and 36 eligible subjects with Acute Myeloid Leukemia (AML). Subjects received tipifarnib 1200 mg to be taken orally with food, twice daily, for 7 days in alternating weeks (Days 1 to 7 and Days 15 to 21) in 28-day cycles. Following amendment 3 subjects (Cohorts 1-4) will receive tipifarnib administered at a dose of 400 mg, orally with food, twice a day (bid) for 21 days in 28-day cycles.

Read the detailed description

This Phase 2 study will investigate the antitumor activity in terms of ORR of tipifarnib in subjects with Myelodysplastic/Myeloproliferative Neoplasias (MDS/MPN cohorts) and Acute Myeloid Leukemia (AML cohorts). For MDS/MPN cohorts, this study will assess the antitumor activity of tipifarnib, in terms of ORR, in subjects with MDS/MPN, including CMML, who have a high ratio of expression of CXCR4 to CXCR2 (CXCR4/2 ratio) in their bone marrow and in those with a low CXCR4/2 ratio. For AML cohorts, this study will assess the antitumor activity of tipifarnib, in terms of ORR, in subjects with AML who have a high ratio of expression of CXCR4 to CXCR2 (CXCR4/2 ratio) in their bone marrow and in those with low CXCR4/2 ratio. Subjects enrolled in the study will consist of patients with KRAS, NRAS wild type status.

  1. Subjects with MDS/MPN with high CXCR4/2 ratio
  2. Subjects with MDS/MPN with low CXCR4/2 ratio
  3. Subjects with AML with high CXCR4/2 ratio
  4. Subjects with AML with low CXCR4/2 ratio
Being tested
Tipifarnib
Medical subject headings
Leukemia, Myelomonocytic, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TipifarnibDrug

    Also called R115777, Zarnestra

    Oral tablet

Study groups in NCT02807272
Study groupRoleWhat they receive
Tipifarnib, OralExperimentalSingle arm
Receives: Drug: Tipifarnib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR)

    The ORR was estimated based on the number of participants who achieved an objective response (OR) (complete response [CR], complete cytogenetic remission [CCR], partial remission [PR], marrow response [MR], or clinical benefit [CB] performed by Principal Investigator according to the MDS/MPN International Working Group [IWG] criteria).

    Measured: Up to 12 months

Secondary outcomes (4)

  1. Duration of Response (DoR)

    DoR was measured from the date the participant first met the criteria of an OR to the date that the participant progressed or until death from any cause during the period of disease assessments. Participants without progression or death were censored at the date of the last disease assessment. Participants who received subsequent anticancer therapy were censored at the date of last disease assessment before subsequent anticancer therapy. The median duration of response and corresponding 95% CI was estimated using the Kaplan Meier method.

    Measured: Up to approximately 15 months

  2. Progression Free Survival (PFS)

    The PFS time was defined as the time from the date of consent signed to the date of documented disease progression or death due to any cause, whichever occurred first. Participants without progression or death were censored at the date of the last disease assessment. Participants who received subsequent anticancer therapy were censored at the date of the last disease assessment before subsequent anticancer therapy. The Kaplan-Meier product-limit method was used to estimate the 1-year PFS rate, as well as the corresponding 95% CI.

    Measured: 1 year

  3. Overall Survival (OS)

    OS time was defined as the time from the date of consent signed to the date of death due to any cause. Participants who were alive or lost to follow-up by the end of the study were censored at the date last known to be alive. The Kaplan-Meier method was used to estimate the proportion (%) of subjects without an event at 12 months, as well as their corresponding 95% CI.

    Measured: Up to approximately 15 months

  4. Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)

    An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with it. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AE severity was rated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.03.: grade 1(mild), grade 2(moderate), grade 3(severe), grade 4(life-threatening), grade 5(death). An AE was considered serious if resulted in any of the following: death, life-threatening, caused inpatient hospitalization or prolonged it, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital abnormality/birth defect, or was an important medical event.

    Measured: Up to approximately 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jun 2016 (estimated)
  2. Study start10 Jan 2017
  3. Primary completion30 Nov 2020
  4. Study completion30 Nov 2020

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
44 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02807272
Sponsor's protocol ID
KO-TIP-004
Acronym
CMML/AML
Status last verified
Jul 2024
First submitted
15 Jun 2016
Last updated
17 Jul 2024
Data monitoring committee
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tipifarnib in people with Leukemia, Myelomonocytic, Chronic, run by Kura Oncology, Inc. at 8 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 18 inclusion and 16 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 17 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 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 phase mean?

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?

Yes. Results are posted in the registry (first posted 17 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Objective Response Rate (ORR) (time frame: Up to 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02807272.

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 17 Jul 2024.

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