A Dose Confirmation Study of Oral Clofarabine for Adult Patients Previously Treated for Myelodysplastic Syndromes (MDS)

NCT00531232 | Completed Phase 2 Results FDA Drug

• 1 other identifier: CLOMDS02507
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 6

Brief Summary

There was no well accepted standard of care for participants who failed or were intolerant to any of the currently approved therapies for myelodysplastic syndromes (MDS). In this study, participants were initially assigned to receive 55 or 35 milligrams (mg) of oral clofarabine daily for 5 days. After safety review of the first participants enrolled, the dose was reduced to 25 milligrams per day (mg/day) for up to 8 cycles as long as the participants continued to benefit and in the absence of progressive disease.

Conditions

Myelodysplastic Syndromes; Secondary Acute Myeloid Leukemia (AML)

Keywords

Previously treated MDS; oral clofarabine; Intermediate-1, Intermediate-2 and High Risk MDS; secondary AML (with history of MDS)

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Overall Response

  Overall Response: complete remission(CR) or marrow CR or partial remission (PR), or hematologic improvement (HI) in participants with myelodysplastic syndromes (MDS);CR or CR with incomplete count recovery(CRi),or PR in participants with secondary acute myeloid leukemia (sAML). Per International Working Group (IWG) criteria, CR:\<= 5% myeloblasts in bone marrow; persistent dysplasia had to be noted; peripheral blood showing hemoglobin (Hgb)\>=11g/dL, platelets \>=100\*10\^9/L,neutrophils \>=1\*10\^9/L, blasts 0%. Marrow CR:\<=5%myeloblasts in bone marrow and decreased by \>=50% over pretreatment; any HI response in peripheral blood. CRi: meeting all criteria for CR except for residual thrombocytopenia (platelet \<100\*10\^9/L) or neutropenia (ANC \<1.0\*10\^9/L). PR: all CR criteria if abnormal before treatment except that marrow blasts should have decreased by \>=50% over pretreatment but still \>5%. HI: meeting any of the erythroid, platelet, or neutrophil improvement categories for at least 8 weeks.

  From date of randomization until disease recurrence or death, whichever occurred first (maximum study duration: up to 4 years)

Secondary Outcomes (13)

• Duration of Response (DoR)

  From first documentation of response to date of documentation of disease relapse, progression or death due to any cause, whichever occurs first (maximum study duration: up to 4 years)

• Number of Participants Who Achieved Hematologic Improvement (HI)

  From date of randomization until disease recurrence or death, whichever occurred first (maximum study duration: up to 4 years)

• Percentage of Participants Achieving Overall Remission (OR)

  From date of randomization until disease recurrence or death, whichever occurred first (maximum study duration: up to 4 years)

• Time to Acute Myeloid Leukemia (AML) Transformation

  From date of randomization until disease recurrence or death, whichever occurred first (maximum study duration: up to 4 years)

• Overall Survival (OS)

  From date of first dose of study drug until date of death due to any cause (maximum study duration: up to 4 years)

Study Arms (3)

Clofarabine 55 mg/day

EXPERIMENTAL

Participants received Clofarabine 55 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).

Drug: Clofarabine

Clofarabine 35 mg/day

EXPERIMENTAL

Participants received Clofarabine 35 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).

Drug: Clofarabine

Clofarabine 25 mg/day

EXPERIMENTAL

Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).

Drug: Clofarabine

Interventions

Clofarabine DRUG

Pharmaceutical form: Tablet, Route of administration: Oral

Also known as: Clolar

Clofarabine 25 mg/day; Clofarabine 35 mg/day; Clofarabine 55 mg/day

Eligibility Criteria

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

You may qualify if:

• Had a pathologically confirmed secondary Acute Myeloid Leukemia (\[sAML\]; following a history of MDS) or MDS with an intermediate-1 (with marrow blasts greater than or equal to \[\>=\] 5%) or intermediate-2 or high risk score as assessed by the International Prognostic Scoring System at study entry. Participants with refractory anemia with excess blasts in transformation recognized by the French-American-British system, and chronic myelomonocytic leukemia were allowed into the study. Pathologic confirmation was the responsibility of the site investigator.
• Had previously treated MDS defined as follows: a) Participants must had at least one, but no more than two, prior treatment regimens \[a.) treatment regimen was defined as any drug or drug combination administered for treatment of MDS with the intent of inducing at least hematologic improvement (consistent with International Working Group criteria); Inadequate treatment, due to drug intolerance or other factors, was considered a prior treatment regimen. Hematopoietic growth factors, hydroxyurea, anti-thymocyte globulin, or supportive care measures (e.g., blood transfusions, immunosuppressive agents, antibiotics) were not considered treatment regimens for the purpose of study entry.\] b.) One of the treatment regimens had to be either 5-azacytidine or decitabine. If 5-azacytidine or decitabine was given as a treatment regimen more than once, it was considered as 2 different treatment regimens. c.) Participants could not be refractory (i.e., progression of disease, or no evidence of response, while on the treatment) to more than one prior treatment regimen (to be considered refractory to decitabine or 5-azacitidine, participants must have received \>= 4 cycles).
• Had documentation of prior transfusion requirements for the preceding 8 weeks (8 weeks prior to first dose of study drug).
• Had Eastern Cooperative Oncology Group performance status 0-2.
• Was able to comply with study procedures and follow-up examinations.
• Had adequate renal and hepatic functions as indicated by predefined laboratory values: a.) Total bilirubin less than or equal to (\<=) 1.5 \* institutional Upper Limit of Normal (ULN) except for unconjugated hyperbilirubinemia secondary to treatment for MDS or Gilbert's syndrome; and b.) Aspartate aminotransferase and Alanine aminotransferase \<= 2.5\*ULN; and c.) Serum creatinine \<= 1.0 milligrams per deciliter, then the estimated glomerular filtration rate (GFR) had to be greater than (\>) 30 mL/min/1.73 m\^2 as calculated by the Modification of Diet in Renal Disease equation.
• Was non-fertile or agreed to use birth control during the study through the end of last treatment visit and at least 90 days after.

You may not qualify if:

• Had an adjustment of dose and/or schedule of erythropoietin, granulocyte colony stimulating factor or other growth factors within 8 weeks prior to the first dose of oral clofarabine.
• Had any prior therapy for treatment of sAML. Hydroxyurea must not have been received within 24 hours prior to first dose of study drug.
• Had any other chemotherapy or any investigational therapy within four weeks of first dose of study drug.
• Had any prior pelvic radiotherapy.
• Had a prior hematopoietic stem cell transplant for MDS.
• Had not recovered to \<= Grade 2 from any drug-related non-hematologic toxicity prior to first dose of the study drug.
• Had an uncontrolled systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
• Had a psychiatric disorder that would interfere with consent, study participation, or follow-up.
• Had any other severe concurrent disease, or had a history of serious organ dysfunction or disease involving the heart, kidney, or liver, in particular: a.) New York Heart Association classification stage II, III, or IV congestive heart failure; b.) Coronary artery disease or arteriosclerotic cardiovascular disease (angina, myocardial infraction) within 3 months of first dose of study drug; c.) Any other primary cardiac disease that, in the opinion of the investigator, increases the risk of ventricular arrhythmia.
• Had any other severe concurrent disease, or had a history of serious organ dysfunction or disease involving the heart had any prior treatment with Clofarabine.
• Had a diagnosis of another malignancy, unless the participants had been disease-free for at least 3 years following the completion of curative intent therapy with the following exceptions: a.) Participants with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease -free duration, were eligible for this study if definitive treatment for the condition had been completed. b.) Participants with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen values were also eligible for this study if hormonal therapy had been initiated or a radical prostatectomy had been performed.
• Had prior positive test for the Human Immunodeficiency Virus.
• Had currently active gastrointestinal disease, or prior surgery that might affect the ability of the participants to absorb oral Clofarabine.
• Participating in other concurrent investigational protocols that were not restricted to data and/or sample collection for participants demographic and/or sample collection for participants demographic and/or disease purposes.
• Had prior treatment with a known nephrotoxic drug within 2 weeks of the first dose of study drug, unless the participants had a calculated GFR \>30 at 2 time points no \<7 days apart during the 2-week period prior to the first dose of study drug.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (6)

The University of Chicago

Chicago, Illinois, 60637, United States

Location

Weill Medical College of Cornell University

New York, New York, 10065, United States

Location

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Baylor University Medical Center Blood Marrow Transplantation Research

Dallas, Texas, 75246, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

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

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Genzyme, a Sanofi Company

Contact-US@sanofi.com

800-633-1610

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2007
• First Posted: September 18, 2007
• Study Start: May 7, 2007
• Primary Completion: May 12, 2011
• Study Completion: May 12, 2011
• Last Updated: March 24, 2022
• Results First Posted: November 2, 2021

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

US (6)