Clofarabine Followed By Lenalidomide for High-Risk Myelodysplastic Syndromes and Acute Myeloid Leukemia

NCT01629082 | Completed Phase 1

• 2 other identifiers: 12014612-H-0146
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• Several types of blood cancer are associated with poor outcomes including high-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and acute myelogenous leukemia (AML). Many people with MDS, CMML, and AML are not candidates for standard treatments. New types of treatment are needed for these cancers.
• Clofarabine and lenalidomide are anticancer drugs. The first damages cancer cells in the body. The second can alter blood supply to abnormal cells or affect how the immune system attacks these cells. These drugs have been previously tested as treatments for MDS and leukemia. However, they have not been tried as a combination for MDS, CMML, and AML. Researchers want to see if these drugs are safe and effective for these types of cancer. Objectives: \- To test the safety and effectiveness of clofarabine and lenalidomide for people with high-risk MDS, CMML, and AML. Eligibility:
• Individuals at least 18 years of age who have high-risk MDS, CMML, and AML.
• Participants must not be candidates for standard treatments. Design:
• Participants will be screened with a physical exam and medical history. Blood and bone marrow samples will be collected.
• Participants will have 5 days of treatment with clofarabine. It will be given through a vein during an inpatient hospital stay. If there are no serious side effects after the infusion, participants will continue treatment as outpatients.
• After 28 days, participants will have a bone marrow biopsy to check their response to treatment.
• After the biopsy, participants will start lenalidomide treatment. Half of the participants will take the drug for 28 days (one treatment cycle). The other half will take it for 56 days (two cycles). More blood tests and biopsies will be used to monitor treatment.
• If there are no serious side effects and the disease does not become worse, participants may keep taking lenalidomide at lower doses for up to 12 more cycles.

Conditions

Myeldysplastic Syndrome (MDS); Chronic Myelomonocytic Leukemia; Bone Marrow Diseases; Neutropenia; Acute Myeloid Leukemia (AML)

Keywords

Myelodysplastic Syndromes; Acute Myeloid Leukemia (AML); Chronic Myelomonocytic Leukemia (CMML)

Outcome Measures

Primary Outcomes (1)

• Identification of the maximum tolerated dose.

Secondary Outcomes (3)

• Overall Survival

• Characterization of response rate and duration

• Feasibility of lenalidomide maintenance therapy

Interventions

Clofarabine DRUG

Lenalidomide DRUG

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than or equal to 18 years old
• Unequivocal diagnosis of MDS (including chronic myelomonocytic leukemia- CMML) according to WHO criteria with IPSS risk categorization for MDS subjects of intermediate-2 to high confirmed by bone marrow evaluation within 30 days prior to study enrollment
• Unequivocal diagnosis of AML according to WHO criteria to include secondary and relapsed or refractory disease confirmed by bone marrow evaluation within 30 days prior to study enrollment
• ECOG Performance Status less than or equal to 2
• Must have failed at least one prior therapy before study enrollment
• Ability to comprehend the investigational nature of the study and provide informed consent
• All study participants must be registered into the mandatory RevAssistRevlimid REMS program, and be willing and able to comply with the requirements of RevAssistRevlimid REMS .
• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 14 days and again within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled within 7 days as required by RevAssistRevlimid REMS ) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMSTM program. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.

You may not qualify if:

• Prior Allogeneic Stem Cell Transplant
• Diagnosis of acute promyelocytic leukemia
• Diagnosis of atypical chronic myeloid leukemia BCR-ABL1 negative, juvenile myelomonocytic leukemia, yelodysplastic/myeloproliferative neoplasm unclassifiable)
• Prior therapy with clofarabine at any dose
• Prior therapy with lenalidomide at doses greater than or equal to 25 milligrams daily
• Clinically significant active infection not responding adequately to therapy
• HIV Positive
• Uncontrolled concurrent hepatic, renal, cardiac, pulmonary, neurologic, infectious, or metabolic disease of such severity, which in the opinion of the PI, would preclude the subjects s ability to tolerate protocol therapy
• Ejection fraction less than 40% by Echocardiogram or MUGA
• Calculated creatinine clearance less 60 milliliters per minute
• Serum bilirubin greater than 1.5 times upper limit of normal
• Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) greater than 3 times upper limit normal
• Decreased oxygen saturation at rest (e.g. pulse oximeter less than 88% or PaO2 less than or equal to 55 millimeters of mercury)
• Patients with any condition that prevents their ability to swallow and retain lenalidomide tablets
• Severe psychiatric illness or complex social situations that would limit the patient s ability to tolerate and/or comply with study requirements

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead
• Celgene Corporation: collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Garcia-Manero G, Fenaux P. Hypomethylating agents and other novel strategies in myelodysplastic syndromes. J Clin Oncol. 2011 Feb 10;29(5):516-23. doi: 10.1200/JCO.2010.31.0854. Epub 2011 Jan 10.

  PMID: 21220589 BACKGROUND

• Aul C, Gattermann N, Schneider W. Age-related incidence and other epidemiological aspects of myelodysplastic syndromes. Br J Haematol. 1992 Oct;82(2):358-67. doi: 10.1111/j.1365-2141.1992.tb06430.x.

  PMID: 1419819 BACKGROUND

• Rollison DE, Howlader N, Smith MT, Strom SS, Merritt WD, Ries LA, Edwards BK, List AF. Epidemiology of myelodysplastic syndromes and chronic myeloproliferative disorders in the United States, 2001-2004, using data from the NAACCR and SEER programs. Blood. 2008 Jul 1;112(1):45-52. doi: 10.1182/blood-2008-01-134858. Epub 2008 Apr 28.

  PMID: 18443215 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Chronic; Bone Marrow Diseases; Neutropenia; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Clofarabine; Lenalidomide

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Agranulocytosis; Leukopenia; Cytopenia; Leukocyte Disorders

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; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Isoindoles

Study Officials

• Sawa Ito, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: June 22, 2012
• First Posted: June 27, 2012
• Study Start: June 6, 2012
• Primary Completion: October 27, 2015
• Study Completion: June 27, 2018
• Last Updated: December 17, 2019

Record last verified: 2018-06-27

Locations

US (1)