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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

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ClinicalTrials.gov Identifier: NCT01729091
Recruitment Status : Recruiting
First Posted : November 20, 2012
Last Update Posted : March 20, 2018
Sponsor:
Collaborators:
Celgene
The Leukemia and Lymphoma Society
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to learn if adding NK cells will help make the stem cell transplant more effective in treating the disease. The safety of this treatment will also be studied.

NK cells may kill myeloma cells that remain in your body after your last chemotherapy treatment. The NK cells are separated from the umbilical cord blood sample. These separated NK cells will then be "grown" (manipulated) in the lab to increase the number of NK cells that can be given to you by vein.

Elotuzumab is designed to directly activate NK cells, that may help kill myeloma cells.

Lenalidomide (Revlimid) is designed to block a protein that plays a role in cell function and growth, which may cause cancer cells to die.

Melphalan is designed to attach to the DNA (genetic material) of cells, which may cause cancer cells to die. It is commonly used in stem cell transplantation.

This is an investigational study. The way researchers make the NK cells is investigational. At this time, it is being used in research only. The NK cell preparation will be provided at no cost to you.

Lenalidomide is FDA approved and commercially available to treat patients with multiple myeloma who have received at least 1 prior therapy.

Melphalan is commercially available and FDA approved for the treatment of myeloma.

Up to 60 participants will be enrolled in this study. All will be enrolled at MD Anderson.


Condition or disease Intervention/treatment Phase
Myeloma Drug: Lenalidomide Drug: Melphalan Procedure: NK Cell Infusion Procedure: Stem Cell Infusion Drug: G-CSF Drug: Elotuzumab Drug: Dexamethasone Phase 1 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : June 2013
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2020


Arm Intervention/treatment
Experimental: Chemotherapy + NK and Stem Cell Infusions

Part I Dose Escalation: From Day -8 to Day -2, lenalidomide 10 mg by mouth daily. On Day -7, high-dose melphalan 200 mg/m^2 by vein. On D-5 NK cell given by vein. On Day 0, autologous stem cell infusion minimum cell dose of 1 x 10^8 cells/kg. G-CSF 5 mcg/kg/day subcutaneously beginning on Day 0, and continuing until evidence of an absolute neutrophil count (ANC) of 0.5 * 109/L per 3 consecutive days.

Elotuzumab 10 mg/kg to be given on day -15 (out-patient) and day -8 (in-patient). Dexamethasone 28 mg by mouth 3 to 24 hours before Elotuzumab infusion plus 8 mg by vein 45 to 90 minutes prior to infusion.

Part I Dose Expansion: Additional 18 high-risk patients treated.

Drug: Lenalidomide
10 mg by mouth daily Day -8 to Day -2.
Other Names:
  • CC-5013
  • Revlimid

Drug: Melphalan
200 mg/m^2 by vein on Day -7.
Other Name: Alkeran

Procedure: NK Cell Infusion

Part I Dose Escalation: Starting dose of Natural Killer (NK) cells 1 x 10^8 cells/kg infused on Day -5.

Part II Dose Expansion: Dose of Natural Killer (NK) cells is MTD from Part I Dose Escalation.


Procedure: Stem Cell Infusion
Autologous stem cell infusion minimum cell dose of 2 e6 cells/kg on Day 0.

Drug: G-CSF
5 mcg/kg/day subcutaneously on Day 0, and continuing until evidence of an absolute neutrophil count (ANC) of 0.5 x 109/L per 3 consecutive days.
Other Names:
  • Filgrastim
  • Neupogen

Drug: Elotuzumab
10 mg/kg by vein to be given on day -15 (out-patient) and day -8 (in-patient).

Drug: Dexamethasone
28 mg by mouth 3 to 24 hours before Elotuzumab infusion plus 8 mg by vein 45 to 90 minutes prior to infusion.
Other Name: Decadron




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of umbilical cord blood (UCB)-derived natural killer (NK) cells [ Time Frame: 30 Days ]
    Maximum tolerated dose (MTD) of UCB-derived NK cells defined as highest dose for which the probability of toxicity is closest to 20%. Dose limiting toxicity (DLT) defined as biopsy proven acute graft versus host disease (GvHD) with overall grade 3 as assessed based on modified Keystone criteria; failure to engraft; or grade 3-4 infusional toxicity of the NK cells.


Secondary Outcome Measures :
  1. Minimal Residual Disease (MRD) Negative r\Rate 100 days Post-Transplant [ Time Frame: 100 days post-transplant ]


Information from the National Library of Medicine

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

Inclusion Criteria:

  1. 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: a. Fluorescence in situ hybridization showing t(4:14), t(14:16)t (14:20 deletion (Del) 17/17p or gain (amp) 1q; b. Deletion 13 by conventional cytogenetic analysis; c. High risk signatures as determined by the GEP-70 or EMC-92 gene expression profiles; d. Relapsed disease within 18 months of prior ASCT.
  2. Patients with plasma cell leukemia who are transplant candidates.
  3. 18 to 75 years of age.
  4. Performance score of at least 70% by Karnofsky or 0 to 2 ECOG.
  5. Adequate major organ system function as demonstrated by: a. Left ventricular ejection fraction greater than 40%. b. Pulmonary function test (PFT) demonstrating a diffusion capacity of least 40% predicted. c. Estimated serum creatinine clearance >/=60 ml/min (using the Cockcroft-Gault formula: creatinine clearance = [(140-age)*kg/(72*serum creatinine)] * 0.85 if female) and/or serum creatinine </=1.6 mg/dL. d. SGPT less than 3 x upper limit of normal. e. Total bilirubin less than 2 x upper limit of normal.
  6. All study participants must be registered into the mandatory Revlimid REMS program, and be willing and able to comply with the requirements of the Revlimid REMS program.
  7. Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS program.
  8. 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.
  9. Patients must have a CB unit available which is matched with the patient at 4, 5, or 6/6 HLA class I (serological) and II (molecular) antigens.
  10. Availability of autologous peripheral blood stem cell graft, containing at least 6.0 x 10^6 CD34+ cells/kg.
  11. Patient or legally authorized representative able to sign informed consent.

Exclusion Criteria:

  1. Patients receiving any other investigational agents.
  2. History of allergic reactions attributed to compounds of similar chemical or biologic composition to melphalan.
  3. Known hypersensitivity or desquamating rash to either thalidomide or lenalidomide.
  4. 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.
  5. HIV-positive patients are excluded due to increased risk of lethal infections when treated with myeloablative chemotherapy.

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, MD, MS, MPH 713-745-9669

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Celgene
The Leukemia and Lymphoma Society
Investigators
Principal Investigator: Rohtesh Mehta, MD, MS, MPH 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: NCI CTRP )
6555-18 ( Other Grant/Funding Number: Leukemia and Lymphoma Society (LLS) )
First Posted: November 20, 2012    Key Record Dates
Last Update Posted: March 20, 2018
Last Verified: March 2018

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

Keywords provided by M.D. Anderson Cancer Center:
Myeloma
Multiple myeloma
MM
Umbilical cord blood
UCB
Natural killer cells
NK
Autologous stem cell transplant
Stem cell infusion
High dose chemotherapy
Lenalidomide
CC-5013
Revlimid
Melphalan
Alkeran
G-CSF
Filgrastim
Neupogen
Elotuzumab
Dexamethasone
Decadron

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, 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
Dexamethasone acetate
Dexamethasone
Lenalidomide
Thalidomide
Melphalan
BB 1101
Lenograstim
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists