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

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ClinicalTrials.gov Identifier: NCT02145403
Recruitment Status : Active, not recruiting
First Posted : May 22, 2014
Last Update Posted : June 4, 2018
Sponsor:
Information provided by (Responsible Party):
University of Michigan Cancer Center

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.

Condition or disease Intervention/treatment Phase
Hematologic Malignancies Relapse Graft-Versus-Host Disease Drug: Carfilzomib Drug: Tacrolimus Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 55 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1/2 Study of Carfilzomib for the Prevention of Relapse and Graft-versus-host Disease in Allogeneic Hematopoietic Cell Transplantation for High-risk Hematologic Malignancies
Study Start Date : September 2014
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : March 2019


Arm Intervention/treatment
Experimental: Carfilzomib
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

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.

Other Name: Kyprolis®

Drug: Tacrolimus
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.




Primary Outcome Measures :
  1. The proportion of patients who are alive and have not developed any "event" [ Time Frame: 1 year ]
    The proportion 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.


Secondary Outcome Measures :
  1. Progression/ Relapse-free survival time [ Time Frame: Up to 3 years ]
    Time from day 0 to the date of the first Progression/ Relapse.

  2. Overall survival time [ Time Frame: Up to 3 years ]
    The time from day 0 to the day of death from any cause.

  3. Number of regimen related toxicities [ Time Frame: Up to 30 days post treatment ]
    The type and number of adverse events related to the study drug.

  4. Cumulative incidence of acute GVHD [ Time Frame: Up to 3 years ]
    The cumulative incidence of acute Graft Versus Host Disease (GVHD)

  5. Cumulative incidence of chronic GVHD [ Time Frame: Up to 3 years ]
    The cumulative incidence of chronic Graft Versus Host Disease (GVHD)

  6. Cumulative incidence of non-relapse mortality [ Time Frame: Up to 3 years ]
    The cumulative incidence of non-relapse mortality



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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]

Exclusion Criteria:

  • 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
  • Subjects with pleural effusion requiring thoracentesis or ascites requiring paracentesis within 14 days prior to admission
  • Uncontrolled psychiatric condition
  • Any other clinically significant medical or psychiatric disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02145403


Locations
United States, Michigan
University of Michigan Hospital
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan Cancer Center
Investigators
Principal Investigator: Attaphol Pawarode, M.D. University of Michgan Cancer Center

Responsible Party: University of Michigan Cancer Center
ClinicalTrials.gov Identifier: NCT02145403     History of Changes
Other Study ID Numbers: UMCC 2014.010
HUM00084170 ( Other Identifier: University of Michigan )
First Posted: May 22, 2014    Key Record Dates
Last Update Posted: June 4, 2018
Last Verified: May 2018

Keywords provided by University of Michigan Cancer Center:
Allogeneic Transplantation
Carfilzomib
Relapse
Graft-Versus-Host Disease
Multiple Myeloma
Lymphoma
Leukemia

Additional relevant MeSH terms:
Neoplasms
Recurrence
Graft vs Host Disease
Disease Attributes
Pathologic Processes
Immune System Diseases
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action