Phase 1/2 Study of Carfilzomib for the Prevention of Relapse and GVHD in Allo-HCT for Hematologic Malignancies

NCT02145403 | Completed Phase 1 Results DMC

• 2 other identifiers: UMCC 2014.010HUM00084170
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators hypothesize that adding carfilzomib to standard conditioning regimen for allo-HCT for advanced or high-risk hematologic malignancies will decrease post-transplant relapse and treatment-related mortality by decreasing severe GVHD, leading to overall improvement in transplant outcomes.

Conditions

Hematologic Malignancies; Relapse; Graft-Versus-Host Disease

Keywords

Allogeneic Transplantation; Carfilzomib; Relapse; Graft-Versus-Host Disease; Multiple Myeloma; Lymphoma; Leukemia

Outcome Measures

Primary Outcomes (2)

• Phase I: Maximum Tolerated Dose (MTD) of Carfilzomib

  Subjects were enrolled on the first dose level (20 mg/m\^2), following a standard 3+3 dose escalation. For any given dose level, if none of the 3 subjects developed a treatment-related dose limiting toxicity (DLT), defined per protocol, dose escalation would follow. If a DLT occurred in any given dose level, the cohort would be expanded to 6. Further dose escalation would be made only if DLTs occurred in \<2 out of 6 subjects. If \>=2 of 6 develop DLTs, dose de-escalation would be made to the previous level. The highest dose level at which no more than one of six participants experience a DLT defines the MTD.

  Up to day 28

• Phase II: Kaplan-Meier Estimate of the Percentage of Patients Who Are Alive and Have Not Developed Any "Event"

  Kaplan-Meier estimate of the percentage of patients who are alive and have not developed relapse/progression of primary disease or clinical grade III-IV acute graft-versus- host disease (GVHD) or chronic GVHD requiring systemic treatment. Subjects who receive all 4 doses of carfilzomib at the maximum tolerated dose level will be considered evaluable for endpoint analysis.

  1 year

Secondary Outcomes (6)

• Phase II: Kaplan-Meier Estimate for Progression/Relapse-free Survival Time

  Up to 3 years

• Phase II: Kaplan-Meier Estimate for Overall Survival Time

  Up to 3 years

• Number of Regimen Related Toxicities (RRTs)

  Up to 30 days post treatment

• Phase II: Cumulative Incidence of Acute GVHD

  At day 180 post-transplant; data collected up to 3 years

• Phase II: Cumulative Incidence of Chronic GVHD

  Up to 3 years

Study Arms (1)

Carfilzomib

EXPERIMENTAL

Carfilzomib will be administered IV over 30 minutes, starting at dose level 1 (20 mg/m2 IV) on Day +1, +2, +6 and +7.

Drug: Carfilzomib; Drug: Tacrolimus

Interventions

Carfilzomib DRUG

Carfilzomib will be administered starting at dose level 1 (20 mg/m2 IV) on day +1, +2, +6 and +7. Dose escalation will be performed on the day +6 and day +7 doses only in each dose level. Day +1 and day+2 doses will be fixed at 20 mg/m2 IV in all dose levels.

Also known as: Kyprolis®

Carfilzomib

Tacrolimus DRUG

Tacrolimus will be administered at 0.03 mg/kg continuous infusion over 24 hours, starting on day -3 as standard graft-versus-host disease prophylaxis.

Carfilzomib

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Lymphoid or Myeloid malignancy requiring allogeneic hematopoietic cell transplantation
• Pathology review by the study institution is required
• Prior high-dose chemotherapy and autologous HCT(s) is (are) allowed
• Disease status: Stable disease or better at the time of enrollment
• Age: \>18 and \<70 years old at the time of transplant (\< 71 years at transplant admission)
• Life expectancy ≥ 6 months after transplant
• A 8/8 or 7/8 HLA-matched donor is available
• Karnofsky Performance Status \>70% (A measure of quality of life that ranges from 0 to 100 where 100 equals perfect health and 0 is death.)
• Adequate cardiac \[LVEF (Left Ventricular Ejection Fraction) \>0.4\], pulmonary \[FEV1 (Forced Expiratory Volume in 1 Second), FVC (Forced Vital Capacity), corrected DLCO (Diffusing Capacity) ≥ 50% predicted\], hepatic \[DB (Direct Bilirubin) \<1.5xULN, AST (Aspartate Aminotransferase) / ALT (Alanine transaminase) ≤3xULN\] and renal function \[GFR (Glomerular Filtration Rate) ≥ 60 mL/min/1.73 m2\]

You may not qualify if:

• Progressive disease
• Active central nervous system involvement by malignancy
• Non compliance to medications or medical instructions
• Lack of appropriate caregivers
• Life expectancy \<6 months
• Pregnant or lactating females
• Uncontrolled infection requiring active treatment (systemic antibiotics, anti-virals, or anti-fungals) within 14 days
• HIV-1/HIV-2 or HTLV-1/HTLV-2 seropositivity
• Active hepatitis A, B or C infection
• Unstable angina or myocardial infarction within 6 months prior to randomization, NYHA Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, uncontrolled or persistent atrial fibrillation/flutter, history of ventricular fibrillation, ventricular tachycardia/torsade de pointes, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker
• History of pulmonary hypertension
• Uncontrolled hypertension or uncontrolled diabetes mellitus
• Non-hematologic malignancy within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen (PSA) levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas
• Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib)
• Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all available anti-microbial drugs or intolerance to IV hydration due to pre-existing pulmonary or cardiac impairment

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (1)

University of Michigan Hospital

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms; Recurrence; Graft vs Host Disease; Multiple Myeloma; Lymphoma; Leukemia

Interventions

carfilzomib; Tacrolimus

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Immune System Diseases; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Attaphol Pawarode, M.D.
• Organization: University of Michigan Rogel Cancer Center

pawarode@med.umich.edu

734-936-8785

Study Officials

• Attaphol Pawarode, M.D.

  University of Michgan Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2014
• First Posted: May 22, 2014
• Study Start: October 1, 2014
• Primary Completion: November 26, 2018
• Study Completion: October 16, 2020
• Last Updated: January 3, 2022
• Results First Posted: January 6, 2020

Record last verified: 2021-12

Locations

US (1)