NCT00038831

Brief Summary

The goal of this clinical research study is to find the highest safe dose of Mylotarg that can be combined with chemotherapy in patients receiving allogeneic bone marrow transplantation. Researchers will study the effects of this treatment combination on patients with high-risk acute leukemia, chronic myelogenous leukemia, or myelodysplastic syndrome. Primary Objective: 1\. To determine the safety and maximum tolerated dose of Mylotarg as part of a reduced-intensity preparative regimen patients undergoing related, mismatched-related or matched unrelated donor transplantation. Secondary Objectives:

  1. 1.To evaluate response rates, engraftment kinetics and degree of chimerism achievable with this strategy.
  2. 2.To evaluate the incidence and severity of GVHD in this population
  3. 3.To evaluate disease-free and overall survival and relapse rates.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
47

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started May 2001

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2001

Completed
1.1 years until next milestone

First Submitted

Initial submission to the registry

June 5, 2002

Completed
2 days until next milestone

First Posted

Study publicly available on registry

June 7, 2002

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2005

Completed
1.6 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2006

Completed
Last Updated

August 1, 2012

Status Verified

July 1, 2012

Enrollment Period

3.8 years

First QC Date

June 5, 2002

Last Update Submit

July 31, 2012

Conditions

Acute Myelogenous LeukemiaMyelodysplastic SyndromeChronic Lymphocytic Leukemia

Keywords

Acute Myelogenous leukemiaAMLMyelodysplastic SyndromeMDSChronic Lymphocytic LeukemiaCMLMylotargGemtuzumabGemtuzumab ozogamicinMelphalanAlkeranFludarabine PhosphateFludarabineFludaraAnti-thymocyte globulinATGAllogeneic Bone MarrowPeripheral Blood Stem Cell TransplantationAllo PBSCTAllogeneic transplantation

Outcome Measures

Primary Outcomes (1)

  • Maximum Tolerated Dose (MTD) of Mylotarg as Determined by Number of Participants With Dose Limiting Toxicity (DLT) at Each Dose Level

    Followed in outpatient clinic from day -12 (prior to transplant) thru day -6 with each dose level

Secondary Outcomes (1)

  • Patient Response

    Continously over first 30 days

Study Arms (1)

Chemotherapy + ATG + Stem Cell Infusion

EXPERIMENTAL
Drug: MylotargDrug: FludarabineDrug: MelphalanDrug: Anti-thymocyte globulinProcedure: Stem cell transplant

Interventions

MylotargDRUG

Starting dose 2 mg/m\^2 over 2-hour intravenous infusion on day -12.

Also known as: Gemtuzumab, Gemtuzumab ozogamicin
Chemotherapy + ATG + Stem Cell Infusion
FludarabineDRUG

30 mg/m\^2 will be given intravenously daily at the same time over 30 minutes on days -5, -4, -3, -2.

Also known as: Fludara, Fludarabine Phosphate
Chemotherapy + ATG + Stem Cell Infusion
MelphalanDRUG

140 mg/m\^2 will be given intravenously over 20 minutes starting 2 hours after the beginning of the fludarabine infusion on day -2.

Also known as: Alkeran
Chemotherapy + ATG + Stem Cell Infusion
Anti-thymocyte globulinDRUG

Patients with an unrelated or mismatched related donor will receive 0.5 mg/kg on day -3 and 1.25 mg/Kg on days -2 and -1, following the chemotherapy.

Also known as: Rabbit anti-thymocyte globulin, Anti-thymocyte globulin (ATG)
Chemotherapy + ATG + Stem Cell Infusion
Stem cell transplantPROCEDURE

Allogeneic Bone Marrow and Peripheral Blood Stem Cell Transplantation: Infusion of blood stem cells or bone marrow cells on day 0.

Also known as: alloBMT, Allo PBSCT
Chemotherapy + ATG + Stem Cell Infusion

Eligibility Criteria

Age12 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Patients 12-75 years of age
  • Patients are eligible if deemed ineligible for conventional high dose chemotherapy programs because of concurrent medical conditions. Patients with refractory AML are always eligible if ejection fraction \> 35, FEV1, FVC, or DLCO \> 40%, abnormal LFT's.
  • Patients must have recovered from previous Grade III-IV toxicity due to prior anti-neoplastic therapy (except alopecia).
  • Patients with the following disease categories will be eligible:
  • AML with induction failure, relapse or 2nd remission
  • MDS with IPI INT-2 or High-risk disease (Appendix 4) or CMML
  • CML in accelerated phase or blast crisis
  • Interferon or STI resistant CML not eligible for conventional stem cell transplant
  • Patients receiving prior BMT are eligible. If myeloablative chemoradiotherapy was used in the prior transplant patients must be \>90 days from transplant. If non-myeloablative therapy was used patients must be \>30 days post-transplant.
  • Leukemia cells must express cell surface CD33 evaluated by flow cytometry in \> 20% of leukemia cells.
  • Patients must have an HLA-compatible related donor (6/6 or 5/6 HLA-match) capable of donating bone marrow or G-CSF stimulated peripheral blood stem cells using aphereses techniques or a 6/6 HLA matched unrelated bone marrow donor (serologic matching for Class I, molecular matching for DR?1).
  • Patients must have a ECOG PS\<2 (Appendix 6), Cr\<2.0, bilirubin \<2, and (SGPT) \<3x normal
  • Patients must have an estimated life expectancy \> 3 months
  • Patient and donor must sign informed consent. Unrelated donors will be consented according to the National Donor Marrow Registry policy

You may not qualify if:

  • uncontrolled active infection
  • HIV disease
  • pregnancy and nursing
  • active, uncontrolled CNS leukemia

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

MeSH Terms

Conditions

Leukemia, Myeloid, AcuteMyelodysplastic SyndromesLeukemia, Lymphocytic, Chronic, B-Cell

Interventions

Gemtuzumabfludarabinefludarabine phosphateMelphalanAntilymphocyte SerumStem Cell Transplantation

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesBone Marrow DiseasesLeukemia, B-CellLeukemia, LymphoidLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

CalicheamicinsAminoglycosidesGlycosidesCarbohydratesAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhenylalanineAmino Acids, AromaticAmino Acids, CyclicAmino AcidsImmune SeraBiological ProductsComplex MixturesCell TransplantationCell- and Tissue-Based TherapyBiological TherapyTherapeuticsTransplantationSurgical Procedures, Operative

Study Officials

  • Marcos De Lima, MD

    M.D. Anderson Cancer Center

    PRINCIPAL INVESTIGATOR

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

June 5, 2002

First Posted

June 7, 2002

Study Start

May 1, 2001

Primary Completion

March 1, 2005

Study Completion

October 1, 2006

Last Updated

August 1, 2012

Record last verified: 2012-07

Locations

US(1)