- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01729091
Umbilical Cord Blood-Derived Natural Killer Cells, Elotuzumab, Lenalidomide, and High Dose Melphalan, Followed by Stem Cell Transplant in Treating Patients With Multiple Myeloma
Phase II Study of Umbilical Cord Blood-Derived Natural Killer Cells in Conjunction With Elotuzumab, Lenalidomide and High Dose Melphalan Followed by Autologous Stem Cell Transplant for Patients With Multiple Myeloma
Study Overview
Status
Conditions
Detailed Description
PRIMARY OBJECTIVES:
I. To find the maximum tolerated dose (MTD) of umbilical cord blood (UCB)-derived natural killer (NK) cells.
II. To determine efficacy by the percent of patients achieving very good partial remission (VGPR) + complete remission (CR) at 3 months post-transplant.
III. To assess the minimal residual disease rate 100 days post-transplant in high-risk patients.
SECONDARY OBJECTIVE:
I. To quantify duration of infused allogeneic donor UCB-derived NK cells in the recipient.
OUTLINE: This is a dose-escalation study of UCB-derived NK cells.
Patients receive elotuzumab intravenously (IV) over 2-5 hours on day -15 and -8, lenalidomide orally (PO) once daily (QD) on days -8 to -2, high-dose melphalan IV over 30 minutes on day -7, and UCB-derived NK cells IV over 1 hour on day -5. Patients undergo autologous stem cell transplant on day 0.
After completion of study treatment, patients are followed up at 30, 60 and 100 days and 6 and 12 months.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- M D Anderson Cancer Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
Patients with high risk multiple myeloma who are transplant candidates, in partial response (PR) or better; high risk will be defined as patients with any of the following:
- Fluorescence in situ hybridization showing t(4:14), t(14:16), t(14:20), gain (amp) 1q; deletion (Del) 17/17p [or tp53 gene mutation/deletion by next generation sequencing (NGS), or by conventional cytogenetics];
- Deletion 13 by conventional cytogenetic analysis;
- High risk signatures as determined by the GEP-70 or EMC-92 gene expression profiles;
- Relapsed disease within 18 months of prior autologous stem cell transplant (ASCT)
- Patients with plasma cell leukemia who are transplant candidates
- Performance score of at least 70% by Karnofsky or 0 to 2 Eastern Cooperative Oncology Group (ECOG)
- Left ventricular ejection fraction greater than 40%
- Pulmonary function test (PFT) demonstrating a diffusion capacity of least 40% predicted
- Estimated serum creatinine clearance >= 60 ml/min (using the Cockcroft-Gault formula and/or serum creatinine =< 1.6 mg/dL
- Serum glutamate pyruvate transaminase (SGPT) less than 3 x upper limit of normal
- Total bilirubin less than 2 x upper limit of normal
- All study participants must be registered into the mandatory Revlimid Risk Evaluation and Mitigation Strategy (REMS) program, and be willing and able to comply with the requirements of the Revlimid REMS program
- Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS program
- Men must agree to use a latex condom during sexual contact with females of child bearing potential even if they have had a successful vasectomy
- Patients must have a cord blood (CB) unit available which is matched with the patient at 4, 5, or 6/6 human leukocyte antigen (HLA) class I (serological) and II (molecular) antigens
- Patient or legally authorized representative able to sign informed consent
Exclusion Criteria:
- Patients receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to melphalan
- Known hypersensitivity or desquamating rash to either thalidomide or lenalidomide
- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, uncontrolled hypertension (systolic > 160, diastolic > 100 despite antihypertensive therapy, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Human immunodeficiency virus (HIV)-positive patients are excluded due to increased risk of lethal infections when treated with myeloablative chemotherapy
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (chemotherapy, UCB-derived NK cells, transplant)
Patients receive elotuzumab IV over 2-5 hours on day -15 and -8, lenalidomide PO QD on days -8 to -2, high-dose melphalan IV over 30 minutes on day -7, and UCB-derived NK cells IV over 1 hour on day -5.
Patients undergo autologous stem cell transplant on day 0.
|
Correlative studies
Given PO
Other Names:
Given IV
Other Names:
Undergo autologous stem cell transplant
Other Names:
Given IV
Other Names:
Given IV
Given IV
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum tolerated dose of umbilical cord blood (UCB)-derived natural killer (NK) cells
Time Frame: Within 30 days post-transplant
|
Defined as the highest dose for which the probability of toxicity is closest to 20%.
Logistic regression methods will be used to model the rate of dose-limiting toxicity as a function of potential prognostic factors (such as demographics, International Staging System stage, and cytogenetic abnormalities).
|
Within 30 days post-transplant
|
Percent of patients achieving very good partial response (VGPR) + complete response (CR)
Time Frame: At 3 months post-transplant
|
Response will be tabulated by dose.
Logistic regression methods will be used to model the rate of VGPR + CR as a function of potential prognostic factors (such as demographics, International Staging System stage, and cytogenetic abnormalities).
Will estimate with a 95 percent credible interval.
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At 3 months post-transplant
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Minimal residual disease (MRD) rate
Time Frame: At 100 days
|
Will model the MRD rate in high-risk patients using logistical regression.
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At 100 days
|
Overall survival (OS)
Time Frame: Up to 12 months
|
OS will be estimated using the Kaplan-Meier product limit estimator, and Cox proportional hazards regression will be used to model OS as functions of the potential prognostic factors.
Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
|
Up to 12 months
|
Progression-free survival (PFS)
Time Frame: Up to 12 months
|
PFS will be estimated using the Kaplan-Meier product limit estimator, and Cox proportional hazards regression will be used to model PFS as functions of the potential prognostic factors.
Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
|
Up to 12 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Duration of infused umbilical cord blood (UCB)-natural killer (NK) cells in new host
Time Frame: Up to 12 months
|
Will be reported as an average time value with standard deviation.
These data may also be used as covariates in the regression models.
|
Up to 12 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Samer S Srour, M.D. Anderson Cancer Center
Publications and helpful links
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
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Leukemia
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Leukemia, Plasma Cell
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Lenalidomide
- Melphalan
- Mechlorethamine
- Nitrogen Mustard Compounds
- Elotuzumab
Other Study ID Numbers
- 2011-0379 (Other Identifier: M D Anderson Cancer Center)
- NCI-2014-01096 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- RV-MM-PI-0691
- NCI-2014-00541
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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