Clofarabine in High Risk Myelodysplastic Syndrome (MDS)

NCT01063257 | Completed Phase 1 DMC

• 1 other identifier: GFM-CLO-08
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 5

Brief Summary

This study aims to determine the maximal tolerated dose (MTD) and dose limiting toxicities (DLTs) of low dose IV clofarabine for MDS patients after treatment failure of azacitidine.

Conditions

Myelodysplastic Syndrome

Keywords

Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• To determine the maximal tolerated dose (MTD) and dose limiting toxicities (DLTs)

  After one course treatment.

  1-2 months

Secondary Outcomes (5)

• To determine response rates.

  1-16 months.

• To evaluate the response duration.

  1-16 months

• To evaluate time to IPSS progression.

  1-16 months

• To evaluate loss of RBC transfusion independence and hospitalization duration.

  1-16 months

• To evaluate rates of rehospitalization for non-hematological toxicities, severe bleeding or febrile neutropenia.

  1-16 months

Study Arms (2)

Cohort A

EXPERIMENTAL

Clofarabine treatment at D1-D5

Drug: Clofarabine

Cohort B

EXPERIMENTAL

Clofarabine treatment at D1, D3, D5, D8, D10

Drug: Clofarabine

Interventions

Clofarabine DRUG

The dosage of Clofarabine will be gradually augmented in a 3+3 design for each following dose level: DL1 - 5mg/m2/d, DL2 - 7.5mg/m2/d, DL3 - 10mg/m2/d, DL4 - 12.5mg/m2/d (This dose may not be reached and is an optional dose level in case the MTD is not reached before and depending on further data from the ongoing MDS Phase IIa oral formulation trial). The DLa will be the following: DL1a - 2.5mg/m2/d, DL2a - 6.5mg/m2/d, DL3a - 8.5mg/m2/d, DL4a - 11.5mg/m2/d (In case of activation of the DL4 step). Dose levels 1a, 2a and 3a will be used for de-escalation.

Also known as: EVOLTRA®

Cohort A; Cohort B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 18 years or more with MDS according to FAB classification and intermediate-2 or high IPSS risk scores, or CMML (with WBC \< 13 x 109/L and bone marrow blasts \> 10 %) according to WHO classification, or AML according to WHO classification if less than 30 % bone marrow blasts (RAEB-T according to FAB MDS classification or AML according to WHO classification with more than 30 % with bone marrow blasts only if preceded by a proven MDS phase.
• ECOG PS ≤ 2.
• Adequate renal and liver function :
• i.e. Serum creatinine \< 110 microM in men or 90 microM in women. If plasma creatinine level \< 90 - 110 microM, then the estimated glomerular filtration rate (GFR) must be \< 50 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease (MDRD) equation where Predicted GFR (mL/min/1.73 m2) = 32788 x (plasma creatinine level (microM)-1.154 x (age in years)-0.023 x (0.742 if patient is female) x (1.212 if patient is African American)
• Bilirubin \< 1.5 x ULN, (except increased unconjugated bilirubin due to dyserythropoiesis).
• Aspartate transaminase (AST)/alanine transaminase (ALT) \< 2.5 × ULN and Alkaline phosphatase \< 2.5 × ULN.
• Absence of pregnancy or lactation in female patients (Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment).
• Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.
• Provided signed written informed consent.
• Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent.

You may not qualify if:

• Patients with AML and bone marrow blasts count of 20-30%, if candidates to intensive AML type chemotherapy.
• Known hypersensitivity to clofarabine or excipients.
• Concomitant malignant disease.
• Active uncontrolled infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
• Concomitant severe cardiovascular disease, i.e. congestive heart failure (NYHA grade \> 3).
• Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.
• No affiliation to a national insurance scheme directly or to an equivalent system.
• Chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
• Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea. The patient must have recovered from all acute toxicities from any previous therapy.

Sponsors & Collaborators

• Groupe Francophone des Myelodysplasies: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (5)

Hôpital Avicenne

Bobigny, 93009, France

Location

Institut Paoli-Calmettes

Marseille, 13009, France

Location

Hôpital Saint-Louis

Paris, 75475, France

Location

Hopital Cochin Service d'Hématologie

Paris, 75679, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Related Links

• Website of the Groupe Francophone des Myélodysplasies (GFM)

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Clofarabine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

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

• Thorsten Braun, MD

  Groupe Francophone des Myélodysplasies

  PRINCIPAL INVESTIGATOR

• Claude Gardin, MD

  Groupe Francophone des Myélodysplasies

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: February 3, 2010
• First Posted: February 5, 2010
• Study Start: April 1, 2010
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: March 19, 2014

Record last verified: 2013-03

Locations

FR (5)