CMS Studies – An Update

1. CMS Studies – An Update CIBMTR Data Managers Meeting February 21, 2018 Sue Logan Clinical Research Coordinator CIBMTR Data Operations

2. Conflict of interest • There are no conflicts of interest to disclose

3. Agenda • What are CMS CED studies? • Current status of CIBMTR’s CMS CED studies • Medicare reimbursement for CED studies

4. Background

5. What is CMS? • Centers for Medicare & Medicaid Services (CMS) is a federal agency within the U.S. Department of Health and Human Services (HHS). • Administers many programs including Medicare.

6. Objective of all CMS studies • To provide a mechanism to Medicare beneficiaries for claims coverage for allogeneic HCT.  • To provide data requested by Medicare under its CED to make payment on claims for HCT using the existing research observational database of the CIBMTR

7. What is CED? • Coverage with Evidence Development (CED) is the means by which CMS can provide coverage and encourage clinical studies that will lead to solid evidence for future decision making. • National Coverage Determination (NCD) • Relatively rare mechanism used when: • Safety has been assured • Service has high potential of benefit • Significant barriers to conduct of trials exist

8. Why is CED needed? • Transplants in the older population continues to increase for a variety of diseases • BMT community continued to work with CMS to consider other CED/NCD • Decisions have been made for: • MDS (Active Dec 2010) • Myelofibrosis (Active Nov 2016) • Multiple Myeloma (Active July 2017) • Sickle Cell (Active Oct 2017)

9. Requirements • Centers must designate willingness to participate in CRF submission for CED • A separate participation agreement is required for each study • Participating recipients must sign CMS consent form

10. CMS Consent • CMS consent form – Feb 2017 • Patients should be invited to participate in both the CMS CED study and the Research Database protocol. • Patient participation in the CMS CED study is not dependent on their participation in the Research Database Protocol.

11. CMS Consent ver 3.0 • Revised consent form was approved by NMDP IRB Jan 2018. • Language was added in Section IV regarding the NIH Certificate of Confidentiality. • Language was added in Section IV regarding submitting health information to scientific databases. • https://www.cibmtr.org/DataManagement/ProtocolConsent/ObservationalData/pages/index.aspx

12. Instructions for Transplant Centers That Use the NMDP/Be The Match IRB • Transplant centers that have an IRB Authorization Agreement with the NMDP IRB may begin using the new consent form immediately for enrolling patients on the CMS CED studies.  No additional local review or approval is necessary.  

13. Instructions for Transplant Centers That Use Their Own Local IRB • If transplant centers use their own local IRB to enroll patients on the CMS CED studies, they should submit the revised protocol and new consent form to their IRB as soon as possible.  • It may be submitted as an amendment so they don’t have to wait until their local IRB continuing review

14. Instructions for Transplant Centers That Use Their Own Local IRB • Centers are allowed to continue using their current consent form while they are obtaining IRB approval of the revised form.   • Renewals must be approved before their local IRB expiration date

15. Instructions for Transplant Centers That Use Their Own Local IRB • Once IRB approval is received, the IRB approval letter and IRB-approved consent form must be sent to Sue Logan at slogan@nmdp.org.

16. Reporting Requirements for all CMS CED studies • CRID assignment form 2804/2814 • Enrollment form 2554

17. Reporting Requirements for all CMS CED studies • Pre-TED form 2400 • Indicate CMS clinical trial 16-CMS-MF • Comprehensive report forms - necessary for study objectives.

18. Assessment of Allogeneic Hematopoietic Stem Cell Transplantation in Medicare Beneficiaries with Myelodysplastic Syndrome and Related disorders - Part I. (10-CMSMDS)

19. 10-CMSMDS • Primary Objective: • To prospectively examine outcomes of allogeneic HCT in adults >= 65 years of age with MDS to determine whether their outcomes are similar to those in younger patients. • Secondary Objectives: • To prospectively determine whether there are disease- or patient-related factors that predict outcomes of HCT for MDS and related disorders in patients >= 65 years of age • To prospectively evaluate what transplant characteristics are associated with outcomes of HCT for MDS and related disorders in patients >= 65 years of age

20. 10-CMSMDS • CMS decision in Summer of 2010 • Opened for enrollment in December 2010 • 134 participating centers • Current Enrollment 3466 • >= 65 y/o Arm = 2181 • <65 Arm = 1285

21. 10-CMSMDS • Patients do not have to have Medicare to be enrolled in the study. • 25% of patients with MDS who gave consent to the research database are enrolled • 100% of patients over age 65 who gave consent to the research database are enrolled • CMS consent and F2554 only required if CMS will be paying for the transplant

22. 10-CMSMDS • As of the January 30th, 2018 release of FormsNet3, centers will be required to complete Comprehensive Report Forms (CRF) for about half of the patients participating in the 10-CMSMDS-1 study. • Further study information is located on the CIBMTR website at the following location: https://www.cibmtr.org/Studies/ClinicalTrials/mct/HCT-MDS/Pages/index.aspx

23. BMT CTN 1102 Hypometh vs RIC for MDS • A Multi-Center Biologic Assignment Trial Comparing Reduced Intensity Allogeneic Hematopoietic Cell Transplant to Hypomethylating Therapy or Best Supportive Care in Patients Aged 50-75 with Intermediate-2 and High Risk Myelodysplastic Syndrome • CTN 1102 is also a CMS CED study • Co-enrollment in 10-CMSMDS and CTN 1102 is not allowed

24. Prospective Assessment of Allogeneic Hematopoietic Cell Transplantation in Patients with Myelofibrosis(16-CMS-MF)

25. 16-CMS-MF HLA-Matched Donor HCT Study • Primary objective: • Compare the five-year survival probabilities from DIPSS assessment between the two study arms: alloHCT recipients and non-HCT therapies (ruxolitinib / best supportive care) recipients. • Secondary objectives: • Compare leukemia-free survival at five years from DIPSS assessment. • Identify patient-, disease-, and HCT-related factors associated with poor HCT outcomes in the alloHCT arm. • Estimate the cumulative incidences of acute and chronic graft-versus-host disease, transplant related mortality, and relapse starting at HCT in the alloHCT arm.

26. 16-CMS-MF Haploidentical Donor Study • Primary objective: • Estimate the five-year overall survival probabilities with haploidentical HCT from DIPSS assessment. • Secondary objectives: • Estimate five-year leukemia-free survival with haploidentical HCT from DIPSS assessment. • Identify patient-, disease-, and HCT-related factors associated with poor outcomes post haploidentical HCT, starting at HCT. • Estimate the cumulative incidences of acute and chronic GVHD, relapse, and transplant related mortality, starting at HCT.

27. 16-CMS-MF • CMS decision in October 2016 • 104 participating centers • Opened for enrollment in December 2016 • Target Enrollment = 650 (225 MAC) • Current Enrollment = 52 • Non-HCT Arm = 2400

28. 16-CMS-MF • Eligibility Criteria • Primary myelofibrosis, post- essential thrombocythemia myelofibrosis, or post- polycythemia vera myelofibrosis. • Int-2 or high-risk disease as determined by the DIPSS. • Age ≥55 at the time of DIPSS. • For the patients receiving an allogeneic transplant: • 6/6 HLA-matched related donors • 8/8 HLA-matched unrelated donor • Haploidentical donor.

29. 16-CMS-MF • Eligibility Criteria • Both peripheral blood stem cells and bone marrow grafts are allowed. • All conditioning regimen intensities are allowed • All GVHD prophylaxis regimens are allowed

30. 16-CMS-MF • Ineligible if • AlloHCT using umbilical cord blood unit(s) • HLA-mismatched adult donors (< 6/6 HLA alleles for related and < 8/8 HLA alleles for unrelated) • Overlap syndromes (e.g., CMML, JMML) • Prior allo HCT

31. Secondary Myelofibrosis • If polycythemia vera or essential thrombocythemia developsmyelofibrosis • On the F2402 • Select polycythemia vera or essential thrombocythemia in Q167 “MDS/MPN subtype at diagnosis” • Q212 Did it transform to a different MDS/MPN subtype should be Yes • Select primary myelofibrosis in Q213 “MDS/MPN subtype after transformation”

32. Dynamic International Prognostic Scoring System (DIPSS) • The Dynamic International Prognostic Scoring System (DIPSS) for primary myelofibrosis (PMF) uses five risk factors to predict survival: • age older than 65 years • hemoglobin lower than 10 g/dL • leukocytes higher than 25 × 10(9)/L • circulating blasts ≥ 1% • constitutional symptoms • weight loss, night sweats, fever

33. Additional Required Forms • F2555 CMS – MF Myelofibrosis Eligibility Form • F2556 Myelofibrosis Supplemental Pre-HCT Data • F2557 Myelofibrosis Supplemental Post-HCT Data

34. Why is my patient on the CRF track when they are not enrolled in the study? • Comprehensive report forms, including the 2556 and 2557,  are now required for all patients with myelofibrosis transplanted after 2/1/2017 • This includes non-Medicare patients and Medicare patients who are not eligible for the study. • Centers that are not participating in the CMS study will be required to submit comprehensive report forms for their myelofibrosis patients. • The only exception to this is when the patient declines consent for CIBMTR’s research database.

35. Assessment of Allogeneic Hematopoietic Cell Transplantation in Medicare Beneficiaries With Multiple Myeloma(17-CMS-MM)

36. 17-CMS-MM • Primary Objective: • To compare five-year OS probabilities between the alloHCT cohort and an age and disease risk matched cohort of autoHCT patients. • Secondary Objectives: • To compare five-year PFS probabilities between the alloHCT cohort and an age and disease risk matched cohort of autoHCT patients.

37. 17-CMS-MM • CMS decision in June 2017 • 71 participating centers • Opened for enrollment in July 2017 • HCT Arm • Target Enrollment = 500 • Current Enrollment = 4 • Control Arm = 500 • Auto HCT patients already in RDB on CRF track

38. 17-CMS-MM • Eligibility Criteria • Stage II or III multiple myeloma at diagnosis • MM Classifications: MM-IgG, MM-IgA, MM-IgD, MM-IgE,MM-IgM (not Waldenstrom),MM-light chain only, MM-non secretory • Are eligible to receive an alloHCT from any suitable allogeneic donor including umbilical cord blood

39. 17-CMS-MM • Exclusion Criteria • Stage 1 at diagnosis • But if they had a prior auto, relapsed within 18 months and then are stage II or III, they will be eligible.

40. BMT CTN 1302 Allo Myeloma • Multicenter Phase II, Double-blind Placebo Controlled Trial of Maintenance Ixazomib after Allogeneic Hematopoietic Stem Cell Transplantation for High Risk Multiple Myeloma • Co-enrollment in 17-CMS-MM and CTN 1302 is allowed

41. Prospective Assessment of Allogeneic Hematopoietic Cell Transplantation in Adolescents and Young Adults with Severe Sickle Cell Disease (17-CMS-SCD)

42. 17-CMS-SCD • Primary Objective: • Compare the 5-year survival probabilities between patients with Sickle Cell Disease (SCD) who received allogeneic HCT to those who received standard of care

43. 17-CMS-SCD • Submitted to CMS in August 2017 • 47 participating centers • Opened for enrollment in Oct 2017 • Target Enrollment = 200 • Current Enrollment = 0 • Non-HCT Arm = 1000

44. 17-CMS-SCD • Eligibility Criteria • Age 15 – 50 years. • Sickle cell disease (HB SS, HB S beta thalassemia or HB SC) with severe signs or symptoms indicating poor prognosis and warranting transplantation. • Stroke • Neurological deficit lasting > 24 hours • Recurrent acute chest syndrome (ACS) • Recurrent pain crises • Red blood cell (RBC) transfusions to prevent vaso-occlusive clinical complications (i.e. pain, stroke, or ACS) • High tricuspid valve regurgitant jet velocity (TRJV)

45. 17-CMS-SCD • Eligibility Criteria • Donors may be HLA-matched unrelated donors, HLA-matched siblings, or mismatched relatives • Donors with sickle cell trait are eligible to donate • Product may be bone marrow, peripheral blood or umbilical cord blood • Exclusion Criteria • Previous allogeneic HCT

46. Additional Required Forms • F2558 CMS – SCD Sickle Cell Disease Eligibility Form

47. BMT CTN 1503 STRIDE2 • A Study to Compare Bone Marrow Transplantation to Standard Care in Adolescents and Young Adults with Severe Sickle Cell Disease • CTN 1503 is also a CMS CED study • Co-enrollment in 17-CMS-SCD and CTN 1503 is not allowed

48. BMT CTN 1507 Haplo SCD • Reduced Intensity Conditioning for Haploidentical Bone Marrow Transplantation in Patients with Symptomatic Sickle Cell Disease • Co-enrollment in 17-CMS-SCD and CTN 1507 is allowed • Enroll patients in both studies if they want Medicare to pay for the transplant. • If the patient is not on Medicare, only enroll them in 1507.

49. Medicare

50. Medicare • There is not a prior authorization process for Medicare CED studies. • The patient must be clinically eligible for the study and have their transplant at a participating center. • When the claim is filed, it must have an approved ICD-10 Diagnosis code and National Clinical Trial number (NCT) listed on the claim.