- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02782546
Cytokine Induced Memory-like NK Cell Adoptive Therapy After Haploidentical Donor Hematopoietic Cell Transplantation
A Phase II Study of Cytokine Induced Memory-like NK Cell Adoptive Therapy After Haploidentical Donor Hematopoietic Cell Transplantation
This is a standard phase 2 study powered to demonstrate improvement in the 100 day leukemia free survival to 30% from <10% expected with the use of reduced intensity haplo-HCT in this extremely high-risk patient cohort (based on the institutional experience using non-myeloablative / reduced intensity conditioning in a similar patient cohort).
A formal safety evaluation will be done after every 6th patient enrolled and the trial will be stopped if noted to have unusually higher engraftment failure (acute GVHD rates (>60% any grades or >30% grade III/IV or ≥ 50% severe cGVHD) or engraftment failure rates (≥15%).
Study Overview
Status
Conditions
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Amanda Cashen, M.D.
- Phone Number: (314) 454-8323
- Email: acashen@wustl.edu
Study Locations
-
-
Missouri
-
Saint Louis, Missouri, United States, 63110
- Recruiting
- Washington University School of Medicine
-
Sub-Investigator:
- Geoffrey Uy, M.D.
-
Sub-Investigator:
- Armin Ghobadi, M.D.
-
Sub-Investigator:
- John Dipersio, M.D., Ph.D.
-
Sub-Investigator:
- Peter Westervelt, M.D., Ph.D.
-
Sub-Investigator:
- Camille Abboud, M.D.
-
Sub-Investigator:
- Keith Stockerl-Goldstein, M.D.
-
Sub-Investigator:
- Ravi Vij, M.D.
-
Sub-Investigator:
- Todd Fehniger, M.D., Ph.D.
-
Sub-Investigator:
- Meagan Jacoby, M.D., Ph.D.
-
Sub-Investigator:
- Iskra Pusic, M.D.
-
Contact:
- Amanda Cashen, M.D.
- Phone Number: 314-454-8323
- Email: acashen@wustl.edu
-
Principal Investigator:
- Amanda Cashen, M.D.
-
Sub-Investigator:
- Mark Schroeder, M.D.
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Recipient Inclusion Criteria:
- Refractory AML without complete remission (CR) after 2 or more cycles of induction therapy (primary induction failure), or AML relapsed after obtaining a CR and failed one or more cycles of re-induction therapy. Standard dose 10-day decitabine (20 mg/m2 daily IV x 10 days) or 7-day azacitidine (75-100 mg/m2 daily SC/IV x 7 days) will be considered as one cycle of induction therapy.
- At least 18 years of age
- Available HLA-haploidentical donor that meets the criteria in the protocol
- Patients with known CNS involvement with AML are eligible provided that they have been treated and CSF is clear for at least 2 weeks prior to enrollment into the study. CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment.
- Karnofsky performance status > 60 %
Adequate organ function as defined below:
- Total bilirubin < 2 mg/dl
- AST(SGOT)/ALT(SGPT) < 3.0 x IULN
- Creatinine within normal institutional limits OR creatinine clearance > 60 mL/min/1.73 m2 by Cockcroft-Gault Formula
- Oxygen saturation ≥90% on room air and adjusted DLCO of at least 40%
- Ejection fraction ≥40%
- Able to be off of corticosteroids (10 mg or less of prednisone or equivalent doses of other systemic steroids are allowed) and any other immune suppressive medications beginning on Day -3
- Women of childbearing potential must have a negative pregnancy test within 28 days prior to study registration. Female and male patients (along with their female partners) must agree to use two forms of acceptable contraception, including one barrier method, during participation in the study and throughout the DLT evaluation period.
- Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Recipient Exclusion Criteria:
- Relapsed after allogeneic transplantation.
- Circulating blast count >30,000/uL by morphology or flow cytometry (cyto-reductive therapies including leukapheresis or hydroxyurea are allowed).
- Uncontrolled bacterial or viral infections, or known HIV, Hepatitis B or C infection.
- Presence of donor specific antibodies (DSA) with Mean Fluorescence Intensity (MFI) of >5000 as assessed by the single antigen bead assay, < 6 weeks prior to starting transplant conditioning
- Uncontrolled angina, severe uncontrolled ventricular arrhythmias, or EKG suggestive of acute ischemia or active conduction system abnormalities.
- New progressive pulmonary infiltrates on screening chest x-ray or chest CT scan that have not been evaluated with bronchoscopy. Infiltrates attributed to infection must be stable/ improving after 1 week of appropriate therapy (4 weeks for presumed or proven fungal infections)
- Known hypersensitivity to one or more of the study agents
- Received any investigational drugs within the 14 days prior to the first day of transplant conditioning
- Pregnant and/or breastfeeding
Donor Inclusion Criteria:
- Related donor (sibling, offspring, or offspring of sibling)
- At least 18 years of age
- HLA-haploidentical donor/recipient match by at least Class I serologic typing at the A&B locus.
- In general good health, and medically able to tolerate leukapheresis required for harvesting the NK cells for this study.
- Ability to understand and willingness to sign an IRB approved written informed consent document
Donor Exclusion Criteria:
- Positive for hepatitis, HTLV, or HIV infection
- Pregnant and/or breastfeeding
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Recipient
|
-Day 0
Other Names:
-GVHD prophylaxis
Other Names:
-GVHD prophylaxis
Other Names:
-Continue until neutrophil engraftment as per institutional guidelines
Other Names:
-Day +7
-Start approximately 4 hours after CIML NK cell infusion
|
Experimental: Donor
|
-Day +6
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Leukemia free survival rate (LFS)
Time Frame: 1 year post transplantation
|
-LFS is defined as the time from achievement of CR to the time of relapse, death in remission, or last follow-up.
|
1 year post transplantation
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Leukemia free survival rate (LFS)
Time Frame: 3 months post transplantation
|
-LFS is defined as the time from achievement of CR to the time of relapse, death in remission, or last follow-up.
|
3 months post transplantation
|
Rate of overall survival (OS)
Time Frame: 1 year post transplantation
|
-OS is defined as the time from the date of Day 0 until death from any cause.
|
1 year post transplantation
|
Incidence of relapse in patients who are found to be CR (complete remission)
Time Frame: Day 28 post transplantation
|
-CR: Morphologically leukemia free state (i.e.
bone marrow with <5% blasts by morphologic criteria and no blasts with Auer rods, no evidence of extramedullary leukemia) and absolute neutrophil count ≥1000 /μL and platelets ≥100,000 /μL.
Patient must be independent of transfusions
|
Day 28 post transplantation
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Amanda Cashen, M.D., Washington University School of Medicine
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Anti-Bacterial Agents
- Adjuvants, Immunologic
- Antibiotics, Antineoplastic
- Antitubercular Agents
- Antibiotics, Antitubercular
- Calcineurin Inhibitors
- Lenograstim
- Tacrolimus
- Mycophenolic Acid
Other Study ID Numbers
- 201610088
- 2P50CA171963-06 (U.S. NIH Grant/Contract)
- 1P50CA171963-01A1 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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