NCT00556452

Brief Summary

The goals of the study are (Phase I) to determine the appropriate dose for Clofarabine with Busulfan as a full-intensity conditioning (Clo/BU4 regimen) prior to transplant and then (Phase II) to investigate the safety and effectiveness of this regimen as a conditioning for stem cell transplant in the treatment of aggressive hematologic malignancies in subjects where more conventional approaches are failing.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
46

participants targeted

Target at P50-P75 for phase_1 leukemia

Timeline
Completed

Started Oct 2007

Typical duration for phase_1 leukemia

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

October 1, 2007

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

November 8, 2007

Completed
4 days until next milestone

First Posted

Study publicly available on registry

November 12, 2007

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2011

Completed
1.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2012

Completed
2.4 years until next milestone

Results Posted

Study results publicly available

January 13, 2015

Completed
Last Updated

December 5, 2017

Status Verified

October 1, 2017

Enrollment Period

3.7 years

First QC Date

November 8, 2007

Results QC Date

November 26, 2014

Last Update Submit

October 30, 2017

Conditions

LeukemiaHodgkin LymphomaNon-Hodgkin LymphomaMultiple MyelomaMyelodysplastic Syndrome

Outcome Measures

Primary Outcomes (2)

  • Regimen Related Toxicities

    The incidence of non-hematological toxicities (Common Terminology Criteria for Adverse Events (CTCAE) 3.0) from initiation of conditioning to Day + 30 or toxicities after day +30, possibly, probably or definitely related to conditioning for all patients treated with Clofarabine (independent of dose level).

    two years

  • One-year Overall Survival Rate for AML

    Percent Overall Survival (OS) for at one year for subjects with Acute Myeloid Leukemia (AML).

    1 year

Secondary Outcomes (2)

  • Two-year Overall Survival for All Cases.

    2 years

  • Five Year Overall Survival for All Cases

    five years

Study Arms (1)

Clo/BU4

EXPERIMENTAL

Study will start at the 2nd dose level of three Clofarabine levels, in combination with Busulfan. The Clofarabine level that each subsequent patient is treated at is determined by a method using continual reassessment. After pre-conditioning, subjects will receive a peripheral blood stem cell transplant.

Drug: Clofarabine/Busulfan x 4Procedure: Peripheral blood stem cell transplantRadiation: Total Lymphoid Irradiation

Interventions

Clofarabine/Busulfan x 4DRUG

Clofarabine IV (dose levels) * 1st dose level: 20 mg/m2/day x 5 days * 2nd dose level: 30 mg/m2/day x 5 days * 3rd dose level: 40 mg/m2/day x 5 days Busulfan IV 3.2 mg/kg daily x 4 days

Clo/BU4
Peripheral blood stem cell transplantPROCEDURE

Peripheral blood stem cell transplant, after pre-conditioning drug treatment

Clo/BU4
Total Lymphoid IrradiationRADIATION

Total Lymphoid Irradiation (TLI) of 4 Gy, if cord blood transplant

Clo/BU4

Eligibility Criteria

AgeUp to 70 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Disease Criteria
  • Acute leukemia or chronic myelogenous leukemia in blastic crisis or accelerated phase, not in remission at the time of transplant
  • Myelodysplastic syndrome, with more than 5% blasts in bone marrow at the time of transplant
  • Hodgkin and Non-Hodgkin Lymphomas: Not in CR in PET scan or CT scan before transplant, or relapsed within 1 year from previous remission
  • CLL not in remission
  • Multiple Myeloma, not in remission
  • Suitable donor available (related or unrelated)
  • Age, Organ Function Criteria
  • Age: ≤ 70 years
  • Cardiac: LV Ejection Fraction ≥ 40% by MUGA or Echocardiogram
  • Pulmonary: FEV1 and FVC ≥ 40% predicted, and DLCO (corrected for hemoglobin) ≥ 40% of predicted
  • Renal: Adult population: serum creatinine ≤ 1.0 mg/dL (if serum creatinine \> 1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be \> 60 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation)
  • Renal: Pediatric population: serum creatinine clearance ≥ 90 ml/min/1.73 m2 as calculated by the Schwartz formula for estimated GFR
  • Hepatic: serum total bilirubin ≤ 2.0 mg/dl and AST / ALT ≤ ULN x 4
  • Performance status: Karnofsky ≥ 70%

You may not qualify if:

  • Other active life-threatening cancer requiring treatment other than allo-HSCT
  • HIV1 or HIV2 positive
  • Uncontrolled medical or psychiatric disorder
  • Uncontrolled viral or fungal infection
  • Active CNS leukemia
  • Non-compliant to medications
  • No appropriate caregivers identified

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Michigan, Department of Internal Medicine, Blood and Marrow Transplant Program

Ann Arbor, Michigan, 48170, United States

Location

Related Publications (1)

  • Magenau J, Tobai H, Pawarode A, Braun T, Peres E, Reddy P, Kitko C, Choi S, Yanik G, Frame D, Harris A, Erba H, Kujawski L, Elenitoba-Johnson K, Sanks J, Jones D, Paczesny S, Ferrara J, Levine J, Mineishi S. Clofarabine and busulfan conditioning facilitates engraftment and provides significant antitumor activity in nonremission hematologic malignancies. Blood. 2011 Oct 13;118(15):4258-64. doi: 10.1182/blood-2011-06-358010. Epub 2011 Aug 12.

    PMID: 21841163DERIVED

MeSH Terms

Conditions

LeukemiaHodgkin DiseaseLymphoma, Non-HodgkinMultiple MyelomaMyelodysplastic Syndromes

Interventions

ClofarabinePeripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphomaLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic DisordersBone Marrow Diseases

Intervention Hierarchy (Ancestors)

Adenine NucleotidesPurine NucleotidesPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsArabinonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesNucleotidesRibonucleotidesHematopoietic Stem Cell TransplantationStem Cell TransplantationCell TransplantationCell- and Tissue-Based TherapyBiological TherapyTherapeuticsTransplantationSurgical Procedures, Operative

Results Point of Contact

Title
Dr. John Magenau
Organization
University of Michigan Cancer Center
johnmage@umich.edu
734/936-8785

Study Officials

  • John Magenau, M.D.

    University of Michigan, Department of Internal Medicine, Blood and Marrow Transplant Program

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes
Restrictive Agreement
No

Study Design

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

Study Record Dates

First Submitted

November 8, 2007

First Posted

November 12, 2007

Study Start

October 1, 2007

Primary Completion

June 1, 2011

Study Completion

September 1, 2012

Last Updated

December 5, 2017

Results First Posted

January 13, 2015

Record last verified: 2017-10

Locations

US(1)