xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06021600</url>
    </required_header>
    <id_info>
      <org_study_id>2023-0134</org_study_id>
      <secondary_id>NCI-2023-06805</secondary_id>
      <nct_id>NCT06021600</nct_id>
    </id_info>
    <brief_title>A Phase 1, Open-Label, Sequential Cross-over, Bioavailability/Bioequivalence Study to Compare the Pharmacokinetics of Oral Cladribine With the Reference Listed Drug, Intravenous Cladribine</brief_title>
    <official_title>A Phase 1, Open-Label, Sequential Cross-over, Bioavailability/Bioequivalence Study to Compare the Pharmacokinetics of Oral Cladribine With the Reference Listed Drug, Intravenous Cladribine</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>M.D. Anderson Cancer Center</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>M.D. Anderson Cancer Center</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        To compare an investigational oral form of the drug cladribine to the FDA approved form of&#xD;
        the drug when it is given by vein (IV).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Objectives:&#xD;
  &#xD;
          -  To compare the pharmacokinetic (PK) properties of oral cladribine (investigational&#xD;
             product) and intravenous (IV) cladribine (reference standard drug) when administered to&#xD;
             patients with hairy-cell leukemia (HCL) or T-cell prolymphocytic leukemia (T-PLL).&#xD;
  &#xD;
        Primary:&#xD;
  &#xD;
          -  To identify a dose of oral cladribine that is bioequivalent to IV cladribine when the IV&#xD;
             dose is administered via a 2-hour infusion to patients with HCL or T-PLL. Area under the&#xD;
             curve (AUC) and maximum concentration (Cmax) will be measured and relative exposure of&#xD;
             oral and IV cladribine will be assessed based on the geometric mean ratio and associated&#xD;
             90% confidence interval for dose-normalized AUCs and Cmax for oral-to-IV cladribine, as&#xD;
             estimated from an appropriate linear mixed effects model.&#xD;
  &#xD;
        Secondary:&#xD;
  &#xD;
          -  To assess the plasma PK of oral cladribine following single-dose and multiple-dose&#xD;
             administration.&#xD;
  &#xD;
          -  To identify a dose of oral cladribine that provides comparable exposure (AUC) to IV&#xD;
             cladribine when the IV dose is administered via a 2-hour infusion to patients with HCL&#xD;
             or T-PLL.&#xD;
  &#xD;
          -  To assess the safety of oral cladribine in patients with HCL or T PLL. No formal&#xD;
             efficacy evaluations will be performed in this study. All patients will be observed for&#xD;
             complete remission (CR), complete remission without minimal residual disease (MRD),&#xD;
             partial response (PR), progressive disease (PD) or stable disease (SD) at the end of the&#xD;
             study, although response is not a study endpoint.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">February 28, 2024</start_date>
    <completion_date type="Anticipated">December 31, 2027</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2025</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Crossover Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0</measure>
      <time_frame>through study completion; an average of 1 year</time_frame>
    </primary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">40</enrollment>
    <condition>Leukemia</condition>
    <condition>Myelodysplastic Syndromes</condition>
    <condition>Acute Myeloid Leukemia</condition>
    <arm_group>
      <arm_group_label>Cohort 1 (Pilot)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will only receive 1 dose of oral cladribine, followed by 4 daily doses of cladribine by vein</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cohort 2 (PK)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will only receive 1 dose of oral cladribine, followed by 4 daily doses of cladribine by vein</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cohort 3 (All-Oral HCL)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will all receive the same dose of oral cladribine over the course of 5 days.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Cladribine</intervention_name>
      <description>Given by PO and Given by IV (vein)</description>
      <arm_group_label>Cohort 1 (Pilot)</arm_group_label>
      <arm_group_label>Cohort 2 (PK)</arm_group_label>
      <arm_group_label>Cohort 3 (All-Oral HCL)</arm_group_label>
      <other_name>Leustatin®</other_name>
      <other_name>2-CdA</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          Study participants must meet the following inclusion criteria&#xD;
  &#xD;
            1. Patients, both men and women of all races and ethnic groups, aged ≥ 18 years are&#xD;
               eligible for enrollment.&#xD;
  &#xD;
            2. Provision of written informed consent prior to any study related procedures.&#xD;
  &#xD;
            3. Patients with newly diagnosed or previously treated HCL who have indication for&#xD;
               therapy and are candidates for cladribine therapy (all 3 cohorts).&#xD;
  &#xD;
            4. Patients with previously treated T-cell prolymphocytic leukemia who have received at&#xD;
               least one course of alemtuzumab-based treatment, who have documented indication for&#xD;
               therapy and who are candidates for cladribine therapy (Cohort 1 and 2) only.&#xD;
  &#xD;
            5. Adequate renal and hepatic organ function as indicated by the following laboratory&#xD;
               values:&#xD;
  &#xD;
                 1. Creatinine clearance ≥ 60 mL/min&#xD;
  &#xD;
                 2. Serum total bilirubin ≤1.5×ULN (with the exception of patients with known&#xD;
                    Gilbert's syndrome: serum total bilirubin must be &lt;3×ULN in these patients)&#xD;
  &#xD;
                 3. Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) and alanine&#xD;
                    aminotransferase (serum glutamic pyruvic transaminase) ≤2.5×ULN or ≤5×ULN if due&#xD;
                    to leukemic involvement).&#xD;
  &#xD;
            6. Adequate cardiac function with a left ventricular ejection fraction ≥45%.&#xD;
  &#xD;
            7. Female patients are eligible to enter and participate in the study if they are of&#xD;
               non-childbearing potential. Female patients of childbearing age must have a negative&#xD;
               pregnancy test at screening and must not be breastfeeding and also agree to use at&#xD;
               least 2 forms of effective birth control during the study treatment period and for at&#xD;
               least 3 months after the last dose of investigational product. (See definitions in&#xD;
               Appendix 2)&#xD;
  &#xD;
            8. Male patients are eligible to enter and participate in the study if they agree to use&#xD;
               effective methods of contraception during the study treatment period and for at least&#xD;
               3 months after the last dose of investigational product. (See definitions in Appendix&#xD;
               2)&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          Study participants must not meet any of the following study exclusion criteria:&#xD;
  &#xD;
            1. Uncontrolled intercurrent illness including, but not limited to ongoing or active&#xD;
               uncontrolled infection, symptomatic congestive heart failure, unstable angina&#xD;
               pectoris, unstable cardiac arrhythmia, malabsorption, or psychiatric illness/social&#xD;
               situations that would limit compliance with study requirements.&#xD;
  &#xD;
            2. History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
               composition to any of the compounds in the study.&#xD;
  &#xD;
            3. Receipt of live or live-attenuated vaccines within 4-6 weeks preceding oral cladribine&#xD;
               treatment, planned during cladribine treatment or after cladribine treatment until the&#xD;
               participant's immune system is no longer weakened (e.g., white blood cell counts are&#xD;
               within normal limits).&#xD;
  &#xD;
            4. Active hepatitis infection, positive hepatitis C antibody, hepatitis B virus surface&#xD;
               antigen or hepatitis B virus core antibody at screening. Patients who are hepatitis C&#xD;
               antibody positive will need to have a negative PCR result prior to enrollment. Those&#xD;
               who are hepatitis C PCR positive will be excluded. Patients who are hepatitis B virus&#xD;
               surface antigen positive or hepatitis B PCR positive will be excluded. Patients who&#xD;
               are anti-HBc antibody positive and who are surface antigen negative will need to have&#xD;
               a negative PCR result before enrollment.&#xD;
  &#xD;
            5. Human immunodeficiency virus (HIV) positive with a viral load &gt;400 copies/mL and a&#xD;
               CD4+ T-cell count of &lt;350 cells/µL or with a history of an acquired immunodeficiency&#xD;
               syndrome (AIDS) opportunistic infection within the past 12 months.&#xD;
  &#xD;
            6. Legal incapacity or limited legal capacity.&#xD;
  &#xD;
            7. Inability to swallow oral medications (capsules and tablets) without chewing,&#xD;
               breaking, crushing, opening or otherwise altering the product formulation.&#xD;
  &#xD;
            8. Patients unwilling to comply with protocol requirements related to the assigned&#xD;
               cohort.&#xD;
  &#xD;
            9. Patients with baseline QTc &gt;470 msec will not be enrolled in Cohort 1. If QTc changes&#xD;
               are observed in response to cladribine in Cohort 1, then the protocol will be amended&#xD;
               to exclude patients with baseline QTc &gt;470 msec from Cohorts 2 and 3, as well&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Farhad Ravandi-Kashani, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>M.D. Anderson Cancer Center</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Farhad Ravandi-Kashani, MD</last_name>
      <phone>(713) 745-0394</phone>
      <email>fravandi@mdanderson.org</email>
    </overall_contact>
    <location>
      <facility>
        <name>M D Anderson Cancer Center</name>
        <address>
          <city>Houston</city>
          <state>Texas</state>
          <zip>77030</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Farhad Ravandi-Kashani, MD</last_name>
        <phone>713-745-0394</phone>
        <email>fravandi@mdanderson.org</email>
      </contact>
      <investigator>
        <last_name>Farhad Ravandi-Kashani, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <link>
      <url>http://www.mdanderson.org</url>
      <description>M D Anderson Cancer Center</description>
    </link>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 28, 2023</study_first_submitted>
    <study_first_submitted_qc>August 28, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 1, 2023</study_first_posted>
    <last_update_submitted>September 11, 2023</last_update_submitted>
    <last_update_submitted_qc>September 11, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Leukemia</mesh_term>
      <mesh_term>Myelodysplastic Syndromes</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Cladribine</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06021600
  org study id: 2023-0134
  secondary id: NCI-2023-06805
  nct id: NCT06021600
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  To compare an investigational oral form of the drug cladribine to the FDA approved form of
        the drug when it is given by vein (IV).
  Objectives:
  
          -  To compare the pharmacokinetic (PK) properties of oral cladribine (investigational
             product) and intravenous (IV) cladribine (reference standard drug) when administered to
             patients with hairy-cell leukemia (HCL) or T-cell prolymphocytic leukemia (T-PLL).
  
        Primary:
  
          -  To identify a dose of oral cladribine that is bioequivalent to IV cladribine when the IV
             dose is administered via a 2-hour infusion to patients with HCL or T-PLL. Area under the
             curve (AUC) and maximum concentration (Cmax) will be measured and relative exposure of
             oral and IV cladribine will be assessed based on the geometric mean ratio and associated
             90% confidence interval for dose-normalized AUCs and Cmax for oral-to-IV cladribine, as
             estimated from an appropriate linear mixed effects model.
  
        Secondary:
  
          -  To assess the plasma PK of oral cladribine following single-dose and multiple-dose
             administration.
  
          -  To identify a dose of oral cladribine that provides comparable exposure (AUC) to IV
             cladribine when the IV dose is administered via a 2-hour infusion to patients with HCL
             or T-PLL.
  
          -  To assess the safety of oral cladribine in patients with HCL or T PLL. No formal
             efficacy evaluations will be performed in this study. All patients will be observed for
             complete remission (CR), complete remission without minimal residual disease (MRD),
             partial response (PR), progressive disease (PD) or stable disease (SD) at the end of the
             study, although response is not a study endpoint.
  allocation: Non-Randomized
  intervention model: Crossover Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
  time frame: through study completion; an average of 1 year
  arm group label: Cohort 1 (Pilot)
  arm group type: Experimental
  description: Participants will only receive 1 dose of oral cladribine, followed by 4 daily doses of cladribine by vein
  arm group label: Cohort 2 (PK)
  arm group type: Experimental
  description: Participants will only receive 1 dose of oral cladribine, followed by 4 daily doses of cladribine by vein
  arm group label: Cohort 3 (All-Oral HCL)
  arm group type: Experimental
  description: Participants will all receive the same dose of oral cladribine over the course of 5 days.
  intervention type: Drug
  intervention name: Cladribine
  description: Given by PO and Given by IV (vein)
  arm group label: Cohort 1 (Pilot)
  arm group label: Cohort 2 (PK)
  arm group label: Cohort 3 (All-Oral HCL)
  other name: Leustatin®
  other name: 2-CdA
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Farhad Ravandi-Kashani, MD
  role: Principal Investigator
  affiliation: M.D. Anderson Cancer Center
  last name: Farhad Ravandi-Kashani, MD
  phone: (713) 745-0394
  email: fravandi@mdanderson.org
  facility: 
  contact: 
  investigator: 
  country: United States
  url: http://www.mdanderson.org
  description: M D Anderson Cancer Center
  responsible party type: Sponsor
  mesh term: Leukemia
  mesh term: Myelodysplastic Syndromes
  mesh term: Cladribine