Busulfan & Melphalan Conditioning for Autologous Stem Cell Transplant (ASCT) and Lenalidomide Maintenance

• Status: Active, not recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

Summary

A number of strategies have been proposed to improve the outcome of ASCT. The three main strategies are to incorporate novel agents into the induction regimen, using maintenance therapy following ASCT and the final strategy is to enhance conditioning regimens.

Investigators would like to explore all these three strategies in this study: Investigators propose to take patients who have had standard novel agent (bortezomib) based induction regimens into this study and then use a dose-adjusted combination of busulfan and melphalan as conditioning regimen and finally Investigators would like to incorporate lenalidomide maintenance post ASCT until disease progression.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Health Network, Toronto
• Collaborators: Celgene Corporation; Otsuka Pharmaceutical Development & Commercialization, Inc.; Princess Margaret Hospital, Canada
• Treatments: Busulfan; Lenalidomide; Melphalan; Thalidomide

Criteria

Inclusion Criteria:

1. Age 18 to 75 years, inclusive.

2. Study participants must have a diagnosis of symptomatic multiple myeloma requiring systemic therapy and are eligible for the planned ASCT.

3. Untreated bone marrow sample was shipped to Princess Margaret Hospital for MRD assay.

4. Must have been treated with a velcade-based induction regimen. No limit to the number of cycles of induction.

5. Study participants in whom the minimum stem cell dose of 2.0 x 106 cluster of differentiation (CD)34+ cells/kg has been collected.

6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.

7. Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test in all females of child-bearing potential (FOCBP).

8. Ability to provide written informed consent prior to initiation of any study-related procedures, and ability, in the opinion of the Principal Investigator, to comply with all requirements of the study.

Exclusion Criteria:

1. Myeloma progression at any time since starting initial induction therapy for multiple myeloma. Changes to or additions to the existing induction therapy are allowed as long as disease progression has not been confirmed.

2. Prior treatment history of ASCT for any medical reason.

3. Prior treatment history of high-dose chemotherapy with stem cell rescue for any medical reason, not limited to myeloma treatment.

4. Prior treatment with busulfan or gemtuzumab ozogamicin for any reason.

5. Systemic amyloidosis.

6. Left ventricular ejection fraction (LVEF) < 45% as measured by either multi-gated acquisition scan (MUGA) or echocardiogram (ECHO) performed within 75 days prior to day of busulfan dose. If cyclophosphamide was used for stem cell harvest, an ECHO or MUGA must be done after the stem cell collection and prior to enrollment to confirm adequate cardiac function.

7. Uncontrolled arrhythmia or symptomatic cardiac disease at the time of screening.

8. Symptomatic pulmonary disease, based on Forced Expiratory Volume in 1 Second (FEV1), Forced Vital Capacity (FVC) or Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) < 50% of predicted (corrected for hemoglobin) measured within 75 days prior to day of busulfan dose.

9. Aspartate transaminase (AST)/alanine transaminase (ALT) ≥ 3 x the upper limit of normal (ULN).

10. History of elevated total serum bilirubin >2 mg/dL that had been caused by previous chemotherapy at any point, or total bilirubin > 2.0 mg/dL at the time of screening with the exception of Gilbert's disease.

11. Hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time as International Normalized Ratio (INR) ≥ 2.0 at the time of screening.

12. Any previous history of fulminant liver failure, cirrhosis, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, and symptomatic biliary disease.

13. Prior total body irradiation therapy, or radiation therapy directly applied to the liver.

14. Patients with a known history of hepatitis B or hepatitis C should be on appropriate anti-viral therapy. Even so, these cases must be discussed with the sponsor and approval obtained prior to screening.

15. Known history of or current HIV infection, or active hepatitis B or c infection or any uncontrolled active infection of any kind at the time busulfan administration.

16. Serum creatinine >177 umol/L at the time of screening.

17. Women who are pregnant or lactating.

18. Current or history of drug and/or alcohol abuse.

19. Use of other investigational therapies within 30 days of enrollment in this study. Use of investigational therapies, other than the ones given as part of this protocol therapy, is not allowed during the study participation.

20. Clinically significant abnormality in medical history or upon examination that might interfere with the outcomes of the study in the opinion of the investigator.

21. Any patient, who in the opinion of the investigator, should not participate in this study.