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Juvenile Myelomonocytic LeukemiaPhase 2NCT00025038

Combination Chemotherapy Followed By Donor Bone Marrow or Umbilical Cord Blood Transplant in Treating Children With Newly Diagnosed Juvenile Myelomonocytic Leukemia

A Phase 2 study testing tipifarnib, isotretinoin and fludarabine phosphate in people with Juvenile Myelomonocytic Leukemia, run by National Cancer Institute (NCI) at 1 site 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

Giving chemotherapy drugs, such as R115777, isotretinoin, cytarabine, and fludarabine, before a donor bone marrow transplant or an umbilical cord transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. Read more about this study

Who is it for?
Ages Up to 18 years
Conditions the study is for
Juvenile Myelomonocytic Leukemia
What is being tested?
tipifarnib, isotretinoin and fludarabine phosphate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
1 siteUnited States
Study dates
Jun 2001to Oct 2007
Phase
Phase 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 Up to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Newly diagnosed, previously untreated juvenile myelomonocytic leukemia
  • Presenting with all of the following:
  • Absence of t(9;22) or bcr/abl by PCR
  • Absolute monocyte count greater than 1,000/mm^3
  • Less than 20% bone marrow blasts
  • Presenting with at least 2 of the following:
Show all 16Show fewer
  • Elevated F hemoglobin
  • Myeloid precursors in peripheral blood
  • WBC greater than 10,000/mm^3
  • Sargramostim (GM-CSF) hypersensitivity
  • See Disease Characteristics
  • Bilirubin no greater than 2.0 mg/dL
  • ALT no greater than 3 times normal
  • Creatinine no greater than 2 times normal
  • No concurrent sargramostim (GM-CSF)
  • No concurrent proton pump inhibitors

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Children's Oncology Group

    Arcadia, California, 91006-3776

Other trials in United States

About this study

Official title: Phase II Window Evaluation of the Farnesyl Transferase Inhibitor (R115777) Followed by 13-CIS Retinoic Acid, Cytosine Arabinoside and Fludarabine Plus Hematopoietic Stem Cell Transplantation in Children With Juvenile Myelomonocytic Leukemia

Giving chemotherapy drugs, such as R115777, isotretinoin, cytarabine, and fludarabine, before a donor bone marrow transplant or an umbilical cord transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. This phase II trial is studying how well giving combination chemotherapy together with donor bone marrow or umbilical cord blood transplant works in treating children with newly diagnosed juvenile myelomonocytic leukemia

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the response rate of children with newly diagnosed juvenile myelomonocytic leukemia treated with R115777, isotretinoin, cytarabine, and fludarabine followed by allogeneic bone marrow or umbilical cord blood transplantation.

II. Determine the safety and toxicity of this regimen in these patients. III. Determine the tolerability of this regimen in these patients. IV. Determine the rate of 2-year event-free survival of patients treated with this regimen.

  1. Determine whether prognostic subsets of these patients can be identified based on expression of clinical, genetic (NFI, monosomy 7, RAS gene), or hematopoietic characteristics.

OUTLINE: This is a multicenter study.

Patients may choose to receive upfront window induction therapy with oral R115777 twice daily on days 1-21. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.

Patients with progressive disease or stable disease with unacceptable hematopoietic recovery after 1 course proceed to induction chemotherapy. (R11577 portion of the study closed to accrual as of 08/2005)

All patients receive induction chemotherapy comprising oral isotretinoin once daily beginning on day 1 and fludarabine IV over 30 minutes and cytarabine IV over 4 hours on days 1-5. Treatment with fludarabine and cytarabine repeats every 28 days for 2 courses. Treatment with isotretinoin continues until allogeneic bone marrow or umbilical cord blood transplantation. Patients with progressive disease after 1 course proceed to transplantation.

After completion of isotretinoin, patients receive a preparative regimen comprising total body irradiation twice daily on days -7 to -4, cyclophosphamide IV over 2 hours on days -3 and -2, and anti-thymocyte globulin IV over 4-6 hours every 12 hours on days -3 to -1. Patients undergo allogeneic bone marrow or umbilical cord blood transplantation on day 0. Patients receive oral isotretinoin daily beginning on approximately day 60 and continuing for 1 year.

Patients are followed every 6 months for 5 years and then annually thereafter.

PROJECTED ACCRUAL: A maximum of 100 patients (18-46 receiving R115777 with induction chemotherapy [R11577 portion of the study closed to accrual as of 08/2005] and 27-54 receiving induction chemotherapy only) will be accrued for this study within 3.2 years.

Being tested
tipifarnib, isotretinoin, fludarabine phosphate, cytarabine, radiation therapy
Medical subject headings
Leukemia, Myelomonocytic, Juvenile

What participants receive

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

  • tipifarnibDrug

    Also called R115777, Zarnestra

    Given orally

  • isotretinoinDrug

    Also called 13-CRA, Amnesteem, Cistane, Claravis

    Given orally

  • fludarabine phosphateDrug

    Also called 2-F-ara-AMP, Beneflur, Fludara

    Given IV

  • cytarabineDrug

    Also called ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U

    Given IV

  • radiation therapyRadiation

    Also called irradiation, radiotherapy, therapy, radiation

    Undergo total body irradiation

  • cyclophosphamideDrug

    Also called CPM, CTX, Cytoxan, Endoxan

    Given IV

  • anti-thymocyte globulinBiological

    Also called ATG, ATGAM, lymphocyte immune globulin, Thymoglobulin

    Given IV

  • allogeneic bone marrow transplantationProcedure or surgery

    Also called bone marrow therapy, allogeneic, bone marrow therapy, allogenic, transplantation, allogeneic bone marrow, transplantation, allogenic bone marrow

    Undergo allogeneic bone marrow transplant

  • double-unit umbilical cord blood transplantationProcedure or surgery

  • umbilical cord blood transplantationProcedure or surgery

    Also called cord blood transplantation, transplantation, umbilical cord blood, UCB transplantation

    Undergo allogeneic cord blood transplant

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00025038
Study groupRoleWhat they receive
Treatment (tipifarnib, bone marrow/umbilical cord transplant)ExperimentalSee detailed description.
Receives: Drug: tipifarnib; Drug: isotretinoin; Drug: fludarabine phosphate; Drug: cytarabine; Radiation: radiation therapy; Drug: cyclophosphamide; Biological: anti-thymocyte globulin; Procedure: allogeneic bone marrow transplantation; Procedure: double-unit umbilical cord blood transplantation; Procedure: umbilical cord blood transplantation; Other: laboratory biomarker analysis

What is being measured

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

  1. Response rate (CR or PR)

    The response rates in the up-front window with respect to whether or not patients had vas activating mutations will also be estimated by proportions.

    Measured: Up to 6 years

  2. Duration of response

    Will be estimated by Kaplan-Meier method.

    Measured: Up to 6 years

  3. Progression-free survival

    Will be estimated by Kaplan-Meier method.

    Measured: 2 years

  4. Evaluation of prognostic importance of genetic marker

    Logrank test and Cox proportional hazards model will be applied.

    Measured: Up to 6 years

  5. Grade 3 or greater toxicities assessed using CTC version 2.0

    Measured: Up to 6 years

Secondary outcomes (2)

  1. Survival of patients receiving the window vs. not

    Measured: Up to 6 years

  2. Response status on end of course reports (pre vs.post)

    Signed-rank comparison of components of therapy will be done.

    Measured: Up to 6 years

Timeline

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

  1. First posted27 Jan 2003 (estimated)
  2. Study startJun 2001
  3. Primary completionOct 2007

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
100 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00025038
Sponsor's protocol ID
NCI-2012-01861
Other IDs
AAML0122, U10CA098543, CDR0000068788
Status last verified
Jan 2013
First submitted
11 Oct 2001
Last updated
11 Apr 2013
Results posted
No

Publications

  • Stieglitz E, Gu CJ, Richardson M, Kita R, Santaguida MT, Ali KA, Strachan DC, Dhar A, Yam G, Anderson W, Anderson E, Hubner J, Tasian SK, Loh ML, Lacher MD. Tretinoin Enhances the Effects of Chemotherapy in Juvenile Myelomonocytic Leukemia Using an Ex Vivo Drug Sensitivity Assay. JCO Precis Oncol. 2023 Sep;7:e2300302. doi: 10.1200/PO.23.00302.

    PubMed 37944074

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing tipifarnib, isotretinoin and fludarabine phosphate in people with Juvenile Myelomonocytic Leukemia, run by National Cancer Institute (NCI) at 1 site 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 16 inclusion and 0 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 11 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

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?

Response rate (CR or PR) (time frame: Up to 6 years). The study lists 5 primary outcomes in all. 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 NCT00025038, which also lists 1 linked publication.

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 11 Apr 2013.

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