NCT04682405
Completed
Phase 2
A Phase II Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate Uproleselan (GMI-1271) for GI Toxicity Prophylaxis During Melphalan-Conditioned Autologous Hematopoietic Cell Transplantation (Auto-HCT) for Multiple Myeloma (MM)
Washington University School of Medicine1 site in 1 country51 target enrollmentStarted: May 5, 2021Last updated:
Overview
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 51
- Locations
- 1
- Primary Endpoint
- Change in Diarrhea as Assessed Per CTCAE v5.0
Overview
Brief Summary
The investigators hypothesize that prophylactic E-selectin inhibition via administration of uproleselan during melphalan conditioning will reduce the gastrointestinal (GI) toxicity in multiple myeloma (MM) patients undergoing auto-transplant, as assessed via diarrhea severity scoring per CTCAE v5.0, while potentially increasing chemosensitivity of malignant MM cells to high-dose melphalan.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Supportive Care
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Biopsy-confirmed multiple myeloma (MM) (per IMWG criteria).
- •Undergoing first auto-HCT for MM in first partial response (PR) or better
- •Conditioning regimen to be single agent melphalan (200 mg/m\^2)
- •Adults 18 to 75 years of age, inclusive
- •ECOG performance status ≤ 2
- •Mobilized ≥ 5.0 x 10\^6 CD34+ cells/kg (i.e. sufficient CD34+ HSCs for one auto-HCT, with at least one back-up graft in reserve)
- •Adequate bone marrow and organ function prior to stem cell mobilization as defined below:
- •Leukocytes, absolute neutrophil count, and platelets within institutional standard limits for high-dose melphalan autologous stem cell transplant
- •Total bilirubin ≤ 1.5 x ULN (unless the patient has a history of Gilbert's Syndrome, in which case, total bilirubin must be ≤ 2.5 times the ULN)
- •AST(SGOT)/ALT(SGPT) ≤ 3.0 x ULN
Exclusion Criteria
- •A history of other malignancy with the exception of malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease.
- •Active signs or symptoms of CNS involvement by malignancy (lumbar puncture not required). Prior history of CNS involvement is acceptable, if patient has completed treatment for CNS involvement with documented treatment response.
- •Prior exposure to uproleselan (GMI-1271)
- •Currently receiving any other investigational agents
- •A history of allergic reactions attributed to compounds of similar chemical or biologic composition to uproleselan or melphalan
- •Known active infection with hepatitis A, B (e.g., HBsAg positive), or C (e.g., anti-HCV positive), or human immunodeficiency virus
- •Uncontrolled acute life-threatening bacterial, viral, or fungal infection-Myocardial infarction within 6 months of uproleselan/placebo dosing, or subject has current significant cardiovascular disease, such as uncontrolled or symptomatic arrhythmias, congestive heart failure, hemodynamic instability, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
- •Any medical, psychiatric, or other condition which, in the opinion of the investigator, unfavorably alters the risk-benefit of subject participation, is likely to interfere with trial completion, assessments, or interpretation of trial results, or otherwise would make the subject an inappropriate subject for this trial.
- •Pregnant and/or breastfeeding.
- •Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective contraception during the trial and for 12 weeks following the last dose of uproleselan/placebo. Women who are postmenopausal with amenorrhea for at least 1 year prior to trial entry and follicle stimulating hormone (FSH) serum levels consistent with postmenopausal status (\>28U/L) will be considered NOT of childbearing potential. Highly effective contraception includes:
Arms & Interventions
Uproleselan + Standard of Care Melphalan
Experimental
- On the evening of Day -3, patients will receive dose #1 of uproleselan
- On the following morning of Day -2 (12 +/- 2 hours from prior dose), patients will receive dose #2 of uproleselan
- On the evening of Day -2 (12 +/- 2 hours from prior dose), patients will receive dose #3 of uproleselan
- On Day -2 following completion of dose #3 of uproleselan, the patient will be administered the conditioning dose of melphalan (200mg/m^2) as per institutional practice.
- On the following morning of Day -1 (12 +/- 2 hours from prior dose), patients will receive dose #4 of uproleselan
- On the evening of Day -1 (12 +/- 2 hours from prior dose), patients will receive dose #5 of uproleselan
- On the following morning of Day 0 (12 +/- 2 hours from prior dose) patients will receive dose #6 (final dose) of uproleselan
- On Day 0, 4 hours (+/- 2 hours) after the final dose of uproleselan, the patient will be infused with the HSC product. The patient will remain inpatient until engraftment
Intervention: Uproleselan (Drug)
Uproleselan + Standard of Care Melphalan
Experimental
- On the evening of Day -3, patients will receive dose #1 of uproleselan
- On the following morning of Day -2 (12 +/- 2 hours from prior dose), patients will receive dose #2 of uproleselan
- On the evening of Day -2 (12 +/- 2 hours from prior dose), patients will receive dose #3 of uproleselan
- On Day -2 following completion of dose #3 of uproleselan, the patient will be administered the conditioning dose of melphalan (200mg/m^2) as per institutional practice.
- On the following morning of Day -1 (12 +/- 2 hours from prior dose), patients will receive dose #4 of uproleselan
- On the evening of Day -1 (12 +/- 2 hours from prior dose), patients will receive dose #5 of uproleselan
- On the following morning of Day 0 (12 +/- 2 hours from prior dose) patients will receive dose #6 (final dose) of uproleselan
- On Day 0, 4 hours (+/- 2 hours) after the final dose of uproleselan, the patient will be infused with the HSC product. The patient will remain inpatient until engraftment
Intervention: Melphalan (Drug)
Placebo + Standard of Care Melphalan
Placebo Comparator
- On the evening of Day -3, patients will receive dose #1 of placebo
- On the following morning of Day -2 (12 +/- 2 hours from prior dose), patients will receive dose #2 of placebo On the evening of Day -2 (12 +/- 2 hours from prior dose), patients will receive dose #3 of placebo.
- On Day -2 following completion of dose #3 of placebo, the patient will be administered the conditioning dose of melphalan (200mg/m^2) as per institutional practice.
- On the following morning of Day -1 (12 +/- 2 hours from prior dose), patients will receive dose #4 of placebo.
- On the evening of Day -1 (12 +/- 2 hours from prior dose), patients will receive dose #5 of placebo.
- On the following morning of Day 0 (12 +/- 2 hours from prior dose) patients will receive dose #6 (final dose) of placebo.
- On Day 0, 4 hours (+/- 2 hours) after the final dose of placebo, the patient will be infused with the HSC product. The patient will remain inpatient until engraftment
Intervention: Placebo (Drug)
Placebo + Standard of Care Melphalan
Placebo Comparator
- On the evening of Day -3, patients will receive dose #1 of placebo
- On the following morning of Day -2 (12 +/- 2 hours from prior dose), patients will receive dose #2 of placebo On the evening of Day -2 (12 +/- 2 hours from prior dose), patients will receive dose #3 of placebo.
- On Day -2 following completion of dose #3 of placebo, the patient will be administered the conditioning dose of melphalan (200mg/m^2) as per institutional practice.
- On the following morning of Day -1 (12 +/- 2 hours from prior dose), patients will receive dose #4 of placebo.
- On the evening of Day -1 (12 +/- 2 hours from prior dose), patients will receive dose #5 of placebo.
- On the following morning of Day 0 (12 +/- 2 hours from prior dose) patients will receive dose #6 (final dose) of placebo.
- On Day 0, 4 hours (+/- 2 hours) after the final dose of placebo, the patient will be infused with the HSC product. The patient will remain inpatient until engraftment
Intervention: Melphalan (Drug)
Outcomes
Primary Outcomes
Change in Diarrhea as Assessed Per CTCAE v5.0
Time Frame: From day -3 to date of discharge or day 14 (whichever is sooner) (up to be 18 days)
Grade 0 is defined as no diarrhea, or no change from baseline. Grade 1 is defined as an increase of \<4 stools per day over baseline; mild increase in ostomy output compared to baseline. Grade 2 is defined as an increase of 4-6 stools per day over baseline; moderate increase in ostomy output compared to baseline; limiting instrumental ADL. Grade 3 is defined as an increase of \>=7 stools per day over baseline; hospitalization indicated; severe increase in ostomy output compared to baseline; limited self care ADL. Grade 4 is defined as life-threatening consequences; urgent intervention indicated. Grade 5 is defined as death.
Secondary Outcomes
- Change in Oral Mucositis as Assessed Per CTCAE v5.0(From day -3 to date of discharge or day 14 (whichever is sooner) (up to be 18 days))
- Change in Nausea as Assessed Per CTCAE v5.0(From day -3 to date of discharge or day 14 (whichever is sooner) (up to be 18 days))
- Change in Esophagitis as Assessed Per CTCAE v5.0(From day -3 to date of discharge or day 14 (whichever is sooner) (up to be 18 days))
- Change in Esophageal Pain as Assessed Per CTCAE v5.0(From day -3 to date of discharge or day 14 (whichever is sooner) (up to be 18 days))
- Change in Abdominal Pain as Assessed Per CTCAE v5.0(From day -3 to date of discharge or day 14 (whichever is sooner) (up to be 18 days))
- Change in Vomiting as Assessed Per CTCAE v5.0(From day -3 to date of discharge or day 14 (whichever is sooner) (up to be 18 days))
- Change in Gastritis as Assessed Per CTCAE v5.0(From day -3 to date of discharge or day 14 (whichever is sooner) (up to be 18 days))
- Change in Enterocolitis as Assessed Per CTCAE v5.0(From day -3 to date of discharge or day 14 (whichever is sooner) (up to be 18 days))
- Change in Proctitis as Assessed Per CTCAE v5.0(From day -3 to date of discharge or day 14 (whichever is sooner) (up to be 18 days))
- Median Change in Scores of Patient Reported Outcomes as Measured by the CTCAE Pro Form v1.0(Day -3, Day +8, date of discharge or Day +14 (whichever is sooner) (up to 18 days))
- Median Change in Scores of Quality of Life as Measured by the CTCAE Pro Form v 1.0(Day -3, Day +8, date of discharge or Day +14 (whichever is sooner) (up to 18 days))
- Change in Hemorrhoids as Assessed Per CTCAE v5.0(From day -3 to date of discharge or day 14 (whichever is sooner) (up to be 18 days))
- Time to Neutrophil Engraftment(Through date of discharge (up to be 18 days))
- Change in Nutritional Status as Assessed by Total Parenteral Nutrition (TPN) Days(Before conditioning and at day +14 or date of discharge (whichever is sooner) (up to be 18 days))
- Duration of Hospital Length of Stay(From date of admission for auto-HCT to date of discharge (up to be 18 days))
- Incidence of Infection Assessed by Rates of Bacteremia (With Organism Reported When Available)(Through date of discharge (upto be 18 days))
- Time to First Antibiotics(Through date of discharge (up to be day 18))
- Median Daily Dose of Anti-diarrheal Medications(Through date of discharge (up to be 18 days))
- Change in Bristol Stool Scale(From day -3 to date of discharge or day 14 (whichever is sooner) (up to be 18 days))
- Change in Nutritional Status as Assessed by Change in Standing Weight(Day -3, Day 8, and date of discharge or Day 14 (whichever is sooner) (up to be 18 days))
- Incidence of Clostridium Difficile Infections(Through date of discharge (up to be 18 days))
- Median Daily Dose of Pain Medications(Through date of discharge (up to be 18 days))
Investigators
Study Sites (1)
Loading locations...
Similar Trials
Terminated
Phase 3
Study to Evaluate the Efficacy of Uproleselan in Combination With Chemotherapy in Chinese Patients With R/R AMLRelapsed/Refractory AMLNCT05054543Apollomics Inc.140
Active, not recruiting
Phase 3
S0820, Adenoma and Second Primary Prevention TrialColorectal NeoplasmsNCT01349881SWOG Cancer Research Network354
Terminated
Phase 1
Uproleselan With Pre-Transplant Conditioning in Hematopoietic Stem Cell Transplantation for AMLAcute Myeloid LeukemiaPediatric CancerNCT05569512Malika Kapadia1
Completed
Phase 2
T4N5 Liposomal Lotion in Preventing The Recurrence of Nonmelanoma Skin Cancer in Patients Who Have Undergone a Kidney TransplantActinic KeratosisBasal Cell Carcinoma of the SkinRecurrent Skin CancerSquamous Cell Carcinoma of the SkinNCT00089180National Cancer Institute (NCI)100
Completed
Phase 2
Prevention of Delayed Graft Function Using Eculizumab Therapy (PROTECT Study)Delayed Graft FunctionNCT02145182Alexion Pharmaceuticals, Inc.288