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

NCT00609739 | Terminated Phase 1 Results DMC

• 3 other identifiers: 1999LS032UMN-MT1999-089906M07303
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Leukemia

Keywords

juvenile myelomonocytic leukemia

Outcome Measures

Primary Outcomes (1)

• Disease-free Survival

  Number of patients who were free of disease and alive at 1 year.

  1 year

Secondary Outcomes (3)

• Patients With Regimen-Related Toxicity

  Up to 30 Days Post Study Treatment

• Patients With Graft-Versus-Host-Disease

  Up to 30 Days Post Study Treatment

• Patients Who Relapsed

  1 Year

Study Arms (1)

Cytarabine + Mitoxantrone

EXPERIMENTAL

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.

Drug: cyclosporine; Drug: cytarabine; Drug: filgrastim; Drug: methotrexate; Drug: methylprednisolone; Drug: mitoxantrone hydrochloride; Procedure: allogeneic bone marrow transplantation; Procedure: umbilical cord blood transplantation; Drug: Cis-Retinoic acid

Interventions

cyclosporine DRUG

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.

Also known as: CSA

Cytarabine + Mitoxantrone

cytarabine DRUG

3000 mg/m\^2 intravenously (IV) over 2 hours x 2 (i.e. total 6000 mg/m\^2/day) on days -9 through -4.

Also known as: Ara-C

Cytarabine + Mitoxantrone

filgrastim DRUG

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.

Also known as: G-CSF

Cytarabine + Mitoxantrone

methotrexate DRUG

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.

Also known as: MTX

Cytarabine + Mitoxantrone

methylprednisolone DRUG

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.

Also known as: Medrol

Cytarabine + Mitoxantrone

mitoxantrone hydrochloride DRUG

10 mg/m\^2 over 30 minutes intravenously (IV) on days -9 through -7.

Also known as: Mitoxantrone

Cytarabine + Mitoxantrone

allogeneic bone marrow transplantation PROCEDURE

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.

Cytarabine + Mitoxantrone

umbilical cord blood transplantation PROCEDURE

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.

Cytarabine + Mitoxantrone

Cis-Retinoic acid DRUG

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.

Also known as: isotretinoin

Cytarabine + Mitoxantrone

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• Active uncontrolled infection within one week of HCT.

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Leukemia; Leukemia, Myelomonocytic, Juvenile

Interventions

Cyclosporine; Cytarabine; Filgrastim; Granulocyte Colony-Stimulating Factor; Methotrexate; Methylprednisolone; Mitoxantrone; Cord Blood Stem Cell Transplantation; Isotretinoin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Proteins; Biological Factors; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Terpenes; Pigments, Biological

Limitations and Caveats

Only 1 patient was enrolled (yr 1999) and later died (yr 2000). Study was terminated due to low accrual.

Results Point of Contact

• Title: Margaret MacMillan, M.D.
• Organization: Masonic Cancer Center, University of Minnesota

macmi002@umn.edu

612-626-2778

Study Officials

• Margaret L. MacMillan, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2008
• First Posted: February 7, 2008
• Study Start: June 1, 1999
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: December 28, 2017
• Results First Posted: March 2, 2012

Record last verified: 2017-12

Locations

US (1)