LEUKERAN, Chlorambucil Form

Chlorambucil (Leukeran®) is an aromatic nitrogen mustard derivative and an alkylating agent. FDA Approved Indication(s) Leukeran is indicated for the treatment of chronic lymphatic (lymphocytic) leukemia, malignant lymphomas including lymphosarcoma, giant follicular lymphoma, and Hodgkin’s disease.
Limitation(s) of use: Leukeran is not curative in any of these disorders but may produce clinically useful palliation. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Leukeran is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Non-Hodgkin Lymphoma (must meet all):

1. One of the following diagnoses (a, b, c, or d): a. Marginal zone lymphoma (i, ii, or iii): i. Splenic marginal zone lymphoma; ii. Nodal marginal zone lymphoma; iii. Extranodal marginal zone lymphoma (a or b): a) Gastric MALT lymphoma; b) Nongastric MALT lymphoma; b. Follicular lymphoma; c. Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL); d. Mycosis fungoides or Sezary syndrome;
2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age ≥ 18 years;
   4. For brand name Leukeran requests, member must use generic chlorambucil, if available, unless contraindicated or clinically significant adverse effects are experienced;

3. Request meets one of the following (a, b, or c):* a. Daily dosing (all indications, including CLL/SLL) (i or ii): i. Dose does not exceed 0.2 mg/kg per day for up to 6 weeks; Page 1 of 6

   CLINICAL POLICY Chlorambucil ii. Dose does not exceed 0.1 mg/kg per day after 6 weeks; b. Intermittent dosing (CLL/SLL), including biweekly or monthly dosing: Dose does not exceed a 0.4 mg/kg initial dose or dose increases of 0.1 mg/kg until response/toxicity is observed; c. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). *Prescribed regimen must be FDA-approved or recommended by NCCN. Approval duration: 6 months
   B. Other diagnoses/indications (must meet 1 or 2):

4. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: HIM.PA.33 for health insurance marketplace and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: HIM.PA.103 for health insurance marketplace and CP.PMN.16 for Medicaid; or
   2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid.
      II. Continued Therapy A. All Indications in Section I (must meet all):
5. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Leukeran for a covered indication and has received this medication for at least 30 days;
6. Member is responding positively to therapy;
   
   3. For brand name Leukeran requests, member must use generic chlorambucil, if available, unless contraindicated or clinically significant adverse effects are experienced;

7. If request is for a dose increase, request meets one of the following (a, b, or c): a. Daily dosing (all indications, including CLL/SLL) (i or ii): i. If member has received ≤ 6 weeks of therapy for the current treatment course: New dose does not exceed 0.2 mg/kg per day for up to a total of 6 weeks per treatment course; ii. If member has received > 6 weeks of therapy for the current treatment course: New dose does not exceed 0.1 mg/kg per day; b. Intermittent dosing (CLL/SLL), including biweekly or monthly dosing: New dose does not exceed a 0.4 mg/kg initial dose or dose increases of 0.1 mg/kg until response/toxicity is observed; c. New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN. Page 2 of 6

   CLINICAL POLICY Chlorambucil Approval duration: 12 months
   B. Other diagnoses/indications (must meet 1 or 2):

8. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: HIM.PA.33 for health insurance marketplace and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: HIM.PA.103 for health insurance marketplace and CP.PMN.16 for Medicaid; or

   2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid.
      III. Diagnoses/Indications for which coverage is NOT authorized:
      A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid or evidence of coverage documents;
      B. Hodgkin lymphoma: Leukeran use in the treatment of Hodgkin lymphoma is no longer supported by NCCN – prescribers are encouraged to consult NCCN treatment guidelines for Hodgkin lymphoma therapies.
      IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key CLL/SLL: chronic lymphocytic leukemia/small lymphocytic lymphoma FDA: Food and Drug Administration NCCN: National Comprehensive Cancer Network Appendix B: Therapeutic Alternatives
      Not applicable Appendix C: Contraindications/Boxed Warnings • Contraindication(s): o Disease has demonstrated prior resistance to Leukeran o Hypersensitivity to Leukeran • Boxed warning(s):
      o Bone marrow suppression o Carcinogen o Mutagenic and teratogenic in humans o Produces human infertility Page 3 of 6

   CLINICAL POLICY Chlorambucil V. Dosage and Administration
   Indication Malignant lymphomas including lymphosarcoma and follicular lymphoma Dosing Regimen Daily dosage: The usual oral dosage is 0.1 to 0.2 mg/kg body weight PO daily for 3 to 6 weeks as required. If maintenance dosage is used, it should not exceed 0.1 mg/kg daily. Chronic lymphatic (lymphocytic) leukemia Daily dosage: The usual oral dosage is 0.1 to 0.2 mg/kg body weight PO daily for 3 to 6 weeks as required. If maintenance dosage is used, it should not exceed 0.1 mg/kg daily. Intermittent dosing: Alternate schedules for the treatment of chronic lymphocytic leukemia employing intermittent, biweekly, or once-monthly pulse doses of chlorambucil have been reported. Intermittent schedules of chlorambucil begin with an initial single dose of 0.4 mg/kg. Doses are generally increased by 0.1 mg/kg until control of lymphocytosis or toxicity is observed. Maximum Dose 0.2 mg/kg/day daily dosing
   0.1 mg/kg/day if maintenance dosing 0.2 mg/kg/day dailiy dosing 0.4 mg/kg/day or higher if itermittent, biweekly, or once-monthly pulse dosing VI. Product Availability
   Tablet: 2 mg VII.