Clinical Trials /

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

NCT01729091

Description:

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. Immunotherapy with monoclonal antibodies, such as elotuzumab, may induce changes in the body's immune system and may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as 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.

Related Conditions:
  • Multiple Myeloma
  • Plasma Cell Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 2011-0379
  • SECONDARY ID: NCI-2014-01096
  • SECONDARY ID: RV-MM-PI-0691
  • SECONDARY ID: NCI-2014-00541
  • SECONDARY ID: 2011-0379
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT01729091

Conditions

  • Plasma Cell Leukemia
  • Plasma Cell Myeloma

Interventions

DrugSynonymsArms
ElotuzumabBMS-901608, Empliciti, HuLuc-63, HuLuc63, PDL-063, PDL063Treatment (chemotherapy, UCB-derived NK cells, transplant)
LenalidomideCC-5013, CC5013, CDC 501, RevlimidTreatment (chemotherapy, UCB-derived NK cells, transplant)
MelphalanAlanine 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-19813Treatment (chemotherapy, UCB-derived NK cells, transplant)
Natural Killer Cell TherapyTreatment (chemotherapy, UCB-derived NK cells, transplant)
Umbilical Cord Blood-Derived Lymphocyte TherapyTreatment (chemotherapy, UCB-derived NK cells, transplant)

Purpose

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. Immunotherapy with monoclonal antibodies, such as elotuzumab, may induce changes in the body's immune system and may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as 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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (chemotherapy, UCB-derived NK cells, transplant)ExperimentalPatients 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.
  • Elotuzumab
  • Lenalidomide
  • Melphalan
  • Natural Killer Cell Therapy
  • Umbilical Cord Blood-Derived Lymphocyte Therapy

Eligibility 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), 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
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose of umbilical cord blood (UCB)-derived natural killer (NK) cells
Time Frame:Within 30 days post-transplant
Safety Issue:
Description: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).

Secondary Outcome Measures

Measure:Duration of infused umbilical cord blood (UCB)-natural killer (NK) cells in new host
Time Frame:Up to 12 months
Safety Issue:
Description:Will be reported as an average time value with standard deviation. These data may also be used as covariates in the regression models.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

October 8, 2019