Expired Study
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Minneapolis, Minnesota 55455


Purpose:

RATIONALE: Giving chemotherapy drugs, such as cytarabine and mitoxantrone, before a donor stem cell transplant helps stop the growth of cancer cells and helps stop the patient's immune system from rejecting the donor's stem cells. When certain 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. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine, methotrexate, and methylprednisolone before or after transplant may stop this from happening. PURPOSE: This phase I/II trial is studying the side effects and best way to give high-dose cytarabine together with mitoxantrone in treating patients with juvenile myelomonocytic leukemia undergoing a second donor stem cell transplant.


Study summary:

OBJECTIVES: Primary - To determine the incidence of 1-year disease-free survival in patients with juvenile myelomonocytic leukemia and who is undergoing a repeat stem cell transplantation. Secondary - To evaluate the incidence of regimen-related toxicity. - To evaluate the incidence of acute and chronic graft-versus-host-disease. - To evaluate the incidence of relapse. OUTLINE: - Preparative cytoreductive therapy: Patients receive high-dose cytarabine IV over 2 hours on days -9 to -4 and mitoxantrone hydrochloride IV over 30 minutes on days -9 to -7. - Allogeneic hematopoietic stem cell transplantation (HSCT): Patients undergo HSCT on day 0. Patients undergoing umbilical cord blood transplantation receive methylprednisolone (as graft failure prophylaxis) IV twice daily on days 5 to 19 followed by a taper every other day thereafter until day 25. - Graft-versus-host-disease (GVHD) prophylaxis: Patients receive cyclosporine IV over 2 hours every 8-12 hours or orally twice daily beginning on day -3 and continuing until day 50, followed by a taper to day 90, in the absence of GVHD. Patients undergoing nongenotypically identical bone marrow transplantation also receive methotrexate IV on day 1 beginning 24 hours after completion of stem cell infusion and on days 3, 6, and 11. - Post-transplantation isotretinoin therapy: Patients receive oral isotretinoin once daily beginning on day 60 and continuing until 1 year after HSCT. Patients undergo bone marrow sample collection on day 21, day 60, day 100, at 6 months, and at 1 year for chimerism studies. Patients also undergo blood sample collection periodically to monitor peripheral blood counts for immune reconstitution. After completion of study treatment, patients are followed on day 21, day 100, at 6 months, and at 1 year.


Criteria:

Inclusion Criteria: - Patients age 0-18 with juvenile myelomonocytic leukemia (JMML) who have relapsed or have residual disease after allogeneic HCT. Residual disease is defined as failure to eradicate original disease without prior documentation of remission. Relapse is defined as reappearance of i) leukocytosis with absolute monocytosis >1 x 10^8/L, ii) presence of immature myeloid cells in the peripheral circulation in two consecutive bone marrow specimens taken at least one month apart, or iii) presence of clonal cytogenetic abnormality. The diagnosis of relapse will be supported by the return of an abnormal cytogenetic marker (if present at diagnosis) or the presence of host cells by RFLP or other method. - Patients should be at least 6 months from first hematopoietic cell transplant (HCT) if clinically stable. (If JMML is rapidly progressive, second HCT may be performed earlier). - Adequate major organ function including: - Cardiac: ejection fraction ≥45% - Pulmonary: FEV >50%, DLCO >50% - Renal: creatinine clearance ≥40 mL/min - Hepatic: no clinical evidence of hepatic failure (e.g. coagulopathy, ascites) - Karnofsky performance status ≥70% or Lansky score ≥50% - Written informed consent. Exclusion Criteria: - Active uncontrolled infection within one week of HCT.


Study is Available At:


Original ID:

1999LS032


NCT ID:

NCT00609739


Secondary ID:

UMN-MT1999-08


Study Acronym:


Brief Title:

Cytosine Arabinoside and Mitoxantrone for Patients With Juvenile Myelomonocytic Leukemia Receiving Repeat Stem Cell Transplantation


Official Title:

Cytosine Arabinoside and Mitoxantrone for Patients With Juvenile Myelomonocytic Leukemia Receiving Repeat Stem Cell Transplantation


Overall Status:

Terminated


Study Phase:

Phase 1/Phase 2


Genders:

N/A


Minimum Age:

N/A


Maximum Age:

18 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Masonic Cancer Center, University of Minnesota


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:

Low accrual


Study Type:

Interventional


Study Design:


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

1


Enrollment Type:

Actual


Overall Contact Information

Official Name:Margaret L. MacMillan, MD
Principal Investigator
Masonic Cancer Center, University of Minnesota

Study Dates

Start Date:June 1999
Completion Date:June 2010
Completion Type:Actual
Primary Completion Date:June 2010
Primary Completion Type:Actual
Verification Date:December 2017
Last Changed Date:December 3, 2017
First Received Date:February 6, 2008
First Results Date:November 22, 2011

Study Outcomes

Outcome Type:Secondary Outcome
Measure:Patients Who Relapsed
Time Frame:1 Year
Safety Issues:False
Description:Number of patients whose disease relapsed.
Outcome Type:Secondary Outcome
Measure:Patients With Graft-Versus-Host-Disease
Time Frame:Up to 30 Days Post Study Treatment
Safety Issues:False
Description:Number of patients who exhibited acute and/or chronic graft-versus-host disease.
Outcome Type:Secondary Outcome
Measure:Patients With Regimen-Related Toxicity
Time Frame:Up to 30 Days Post Study Treatment
Safety Issues:False
Description:Number of patients with adverse events related to treatment.
Outcome Type:Primary Outcome
Measure:Disease-free Survival
Time Frame:1 year
Safety Issues:False
Description:Number of patients who were free of disease and alive at 1 year.

Study Interventions

Intervention Type:Drug
Name:cyclosporine
Description:Patients will receive CSA therapy beginning on day -3, with a taper commencing on day +60 (unless GVHD) and ending on day +90. For patients >40 kg with normal renal function (creatinine <1.3 mg/dL), the initial dose will be 2.5 mg/kg intravenously (IV) over 2 hours every 12 hours. For children <40 kg, the initial dose will be 2.5 mg/kg IV over 2 hours every 8 hours.
Arm Name:Cytarabine + Mitoxantrone
Other Name:CSA
Intervention Type:Drug
Name:cytarabine
Description:3000 mg/m^2 intravenously (IV) over 2 hours x 2 (i.e. total 6000 mg/m^2/day) on days -9 through -4.
Arm Name:Cytarabine + Mitoxantrone
Other Name:Ara-C
Intervention Type:Drug
Name:filgrastim
Description:Patients with absolute neutrophil count (ANC) <0.2 x 10^8/L on day 21 may receive G-CSF at 5 mcg/kg/day. G-CSF will be continued until ANC ≥2.5 x 10^8/L for two consecutive days. As the malignant cell population of JMML is known to be hypersensitive to GM-CSF, this cytokine will not be given to these patients.
Arm Name:Cytarabine + Mitoxantrone
Other Name:G-CSF
Intervention Type:Drug
Name:methotrexate
Description:MTX will be administered to recipients of non-genotypically identical BMT. MTX will be administered at a dose of 15 mg/m^2 (based on adjusted ideal body weight) intravenously (IV) on day +1 and at a dose of 10 mg/m^2 IV on days +3, +6, and +11.
Arm Name:Cytarabine + Mitoxantrone
Other Name:MTX
Intervention Type:Drug
Name:methylprednisolone
Description:Recipients of UCB will receive methylprednisolone 2 mg/kg/day from day +5 to +19 at a dose of 1 mg/kg twice a day (bid) with a 10% taper every week thereafter.
Arm Name:Cytarabine + Mitoxantrone
Other Name:Medrol
Intervention Type:Drug
Name:mitoxantrone hydrochloride
Description:10 mg/m^2 over 30 minutes intravenously (IV) on days -9 through -7.
Arm Name:Cytarabine + Mitoxantrone
Other Name:Mitoxantrone
Intervention Type:Procedure
Name:allogeneic bone marrow transplantation
Description:Donor marrow will be collected in the usual sterile manner with a collection goal of 2.0 >10^8/kg recipient weight. Infused on Day 0.
Arm Name:Cytarabine + Mitoxantrone
Intervention Type:Procedure
Name:umbilical cord blood transplantation
Description:Umbilical cord blood (UCB) will be cryopreserved prior to transplantation. Cord blood units will be selected for transplantation according to current University of Minnesota Department of Blood and Marrow Transplantation Guidelines.
Arm Name:Cytarabine + Mitoxantrone
Intervention Type:Drug
Name:Cis-Retinoic acid
Description:Post-Transplant Cis-Retinoic Acid (CRA) Therapy - CRA will be given at a dosage of 100 mg/m^2/day by mouth in a single daily dose starting on day +60 and continuing until 1 year after transplant.
Arm Name:Cytarabine + Mitoxantrone
Other Name:isotretinoin

Study Arms

Study Arm Type:Experimental
Arm Name:Cytarabine + Mitoxantrone
Description:This is a phase I-II study designed to evaluate the efficacy of the administration of high dose cytosine arabinoside and mitoxantrone followed by HCT in patients with JMML who have residual disease or have relapsed after initial HCT.

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:Masonic Cancer Center, University of Minnesota

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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