Allogeneic Stem Cell Transplant With Clofarabine, Ara-C and TBI for AML and ALL

NCT00529360 | Completed Phase 1 DMC

• 1 other identifier: L 9471
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Hypothesis: Myeloablative conditioning using a dose escalation of clofarabine in combination with cytarabine (ARA-C) and total body irradiation (TBI) will lead to improved survival for previously untransplanted children and adolescents with acute lymphoblastic leukemia (ALL) and acute non-lymphoblastic leukemia (ANLL)followed by allogeneic stem cell transplantation (AlloSCT).

Conditions

Acute Lymphoblastic Leukemia; Acute Myelogenous Leukemia

Keywords

Acute Leukemia; Allogeneic Stem Cell Transplant; Clofarabine; Acute Lymphoblastic Leukemia; Acute Myelogenous Leukemia

Outcome Measures

Primary Outcomes (3)

• To determine the maximum tolerated dose (MTD) and/or the safe, tolerated dose of clofarabine in combination with ARA-C and TBI followed by AlloSCT in children with ALL and ANLL.

  2.5 years

• To define the toxicity and safety of the conditioning regimen of clofarabine, ARA-C, TBI followed by AlloSCT in children with ALL and ANLL.

  2.5 years

• To define the pharmacokinetics of clofarabine given in combination with ARA-C and TBI followed by AlloSCT in children with ALL and ANLL.

  2.5 years

Secondary Outcomes (3)

• To determine the event-free, disease-free and overall survival of the conditioning regimen of clofarabine, ARA-C and TBI followed by AlloSCT in children with ALL and AML.

  5 years

• To estimate the time to hematopoietic reconstitution, stratified by cell source, following clofarabine, ARA-C and TBI followed by AlloSCT in children with ALL and AML.

  2.5 years

• To measure the changes in minimal residual disease with ALL and AML following clofarabine, ARA-C and TBI followed by AlloSCT

  5 years

Study Arms (2)

Part A

EXPERIMENTAL

Part A will be the dose escalation phase to determine the MTD and/or safe/tolerated dose of clofarabine.

Drug: Clofarabine

Part B

EXPERIMENTAL

Part B will accrue patients to further define the event free, disease free and overall survival at the MTD or safe/tolerated dose of clofarabine.

Drug: Clofarabine

Interventions

Clofarabine DRUG

Dose escalation of clofarabine on Days -9, -8, -7, -6, -5: 1 - 30 mg/m2; 2 - 40 mg/m2; 2 - 46 mg/m2; 3 - 52 mg/m2

Also known as: Clolar®

Part A

Eligibility Criteria

• Age: Up to 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age: Patients must be \<30 years of age.
• Disease Status: ALL in relapse, induction failure, CR3, or CR3P (Part A ONLY); AML in relapse, induction failure, CR3, or CR3P (Part A ONLY); ALL in CR3 or CR3P (Part A and Part B); AML in CR3 or CR3P (Part A and BONLY); CR3/CR3P must be documented by bone marrow and CNS assessment within 14 days of initiation of the pre-transplant conditioning regimen.
• Creatinine clearance \>40 ml/min/m2 or \>60 ml/min/1.73 m2 or an equivalent radioisotope glomerular filtration rate (GFR) as determined by the institutional normal range or serum creatinine based on age
• Adequate liver function defined as: Total bilirubin \<2.5 mg/dl l, or SGOT (AST) or SGPT (ALT) \<5 x upper limit of normal
• Adequate cardiac function defined as: Shortening fraction \>27% by echocardiogram, or Ejection fraction of \>50% by radionuclide angiogram or echocardiogram.
• Adequate pulmonary function defined as: Corrected DLCO \>60% by pulmonary function test; For children who are uncooperative, no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry \>94% on room air.
• Performance Status: For patients age 1-16 years, Lansky score of \>60; For patients \> 16 years, Karnofsky score of \>60.
• Patients must have received a minimum of one round of re-induction and one round of consolidation chemotherapy after relapse #2

You may not qualify if:

• Patients with prior myeloablative allogeneic stem cell transplantation and /or TBI.
• Females who are pregnant (positive HCG) or lactating.
• Karnofsky \<60% or Lansky \<60% if less than 16 years of age
• Age \>30 years of age
• Any patient with uncontrolled infection prior to study entry
• Patients with evidence of active disease.
• Patients with Down syndrome are excluded

Sponsors & Collaborators

• New York Medical College: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (1)

New York Medical College

Vallhala, New York, 10595, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute

Interventions

Clofarabine

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides

Study Officials

• Mitchell S Cairo

  New York Medical College

  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: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 11, 2007
• First Posted: September 14, 2007
• Study Start: June 1, 2007
• Primary Completion: January 1, 2016
• Study Completion: March 1, 2016
• Last Updated: March 24, 2016

Record last verified: 2016-03

Locations

US (1)