ClinicalTrials.gov
ClinicalTrials.gov Menu

Umbilical Cord Blood-Derived Natural Killer Cells, Elotuzumab, Lenalidomide, and High Dose Melphalan, Followed by Stem Cell Transplant in Treating Patients With Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01729091
Recruitment Status : Recruiting
First Posted : November 20, 2012
Last Update Posted : November 7, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
This phase II trial studies the side effects and best dose of umbilical cord blood-derived natural killer cells when given together with elotuzumab, lenalidomide, and high dose melphalan before autologous stem cell transplant and to see how well they work in treating patients with multiple myeloma. Before transplant, stem cells are taken from patients and stored. Drugs used in chemotherapy, such as elotuzumab, lenalidomide, and melphalan, may work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before a stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Giving natural killer cells from donor umbilical cord blood before transplant may also kill myeloma cells that remain in the body after the last chemotherapy treatment. After treatment, stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.

Condition or disease Intervention/treatment Phase
Plasma Cell Leukemia Plasma Cell Myeloma Procedure: Autologous Hematopoietic Stem Cell Transplantation Biological: Elotuzumab Other: Laboratory Biomarker Analysis Drug: Lenalidomide Drug: Melphalan Biological: Natural Killer Cell Therapy Biological: Umbilical Cord Blood-Derived Lymphocyte Therapy Phase 2

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 OBJECTIVES:

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 on days 30 and 100.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/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
Actual Study Start Date : June 10, 2013
Estimated Primary Completion Date : June 28, 2019
Estimated Study Completion Date : June 28, 2019


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.
Procedure: Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous stem cell transplant
Other Names:
  • Autologous Hematopoietic Cell Transplantation
  • autologous stem cell transplantation

Biological: Elotuzumab
Given IV
Other Names:
  • BMS-901608
  • Empliciti
  • HuLuc-63
  • HuLuc63
  • PDL-063
  • PDL063

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Lenalidomide
Given PO
Other Names:
  • CC-5013
  • CC5013
  • CDC 501
  • Revlimid

Drug: Melphalan
Given IV
Other Names:
  • Alanine Nitrogen Mustard
  • CB-3025
  • L-PAM
  • L-Phenylalanine Mustard
  • L-sarcolysin
  • L-Sarcolysin Phenylalanine mustard
  • L-Sarcolysine
  • Melphalanum
  • Phenylalanine Mustard
  • Phenylalanine nitrogen mustard
  • Sarcoclorin
  • Sarkolysin
  • WR-19813

Biological: Natural Killer Cell Therapy
Given IV

Biological: Umbilical Cord Blood-Derived Lymphocyte Therapy
Given IV




Primary Outcome Measures :
  1. Maximum tolerated dose of umbilical cord blood (UCB)-derived natural killer (NK) cells defined as the highest dose for which the probability of toxicity is closest to 20% [ Time Frame: Within 30 days post-transplant ]
    Logistic regression methods will be used to model the rate of dose-limiting toxicity as a function of potential prognostic factors (such as International Staging System stage, cytogenetic abnormalities).

  2. 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 International Staging System stage, cytogenetic abnormalities). Will estimate with a 95 percent credible interval.

  3. Minimal residual disease (MRD) rate [ Time Frame: At 100 days ]
    Will model the MRD rate in high-risk patients using logistical regression.

  4. Overall survival (OS) [ Time Frame: Up to 100 days ]
    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.

  5. Progression-free survival (PFS) [ Time Frame: Up to 100 days ]
    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.


Secondary Outcome Measures :
  1. Duration of infused umbilical cord blood (UCB)-natural killer (NK) cells in new host [ Time Frame: Up to 100 days ]
    Will be reported as an average time value with standard deviation. This information may later be subject to chi-square or t-test analysis to determine association with response rate.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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) deletion (Del) 17/17p or gain (amp) 1q;
    • 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 Cockroft-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
  • Availability of autologous peripheral blood stem cell graft, containing at least 6.0 x 10^6 cluster of differentiation 34 positive (CD34+) cells/kg except those with relapsed disease within 18 months of prior ASCT, who should have at least 2.5 x 10^6 CD34+ cells/kg available
  • 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

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): NCT01729091


Contacts
Contact: Rohtesh Mehta 713-745-9669 rmehta1@mdanderson.org

Locations
United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Rohtesh S. Mehta    713-745-9669      
Principal Investigator: Rohtesh S. Mehta         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Rohtesh Mehta M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01729091     History of Changes
Other Study ID Numbers: 2011-0379
NCI-2014-01096 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NCI-2014-00541
RV-MM-PI-0691
2011-0379 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: November 20, 2012    Key Record Dates
Last Update Posted: November 7, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Leukemia, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Leukemia
Lenalidomide
Thalidomide
Melphalan
Mechlorethamine
Nitrogen Mustard Compounds
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Immunosuppressive Agents
Leprostatic Agents