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.
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
- NCT ID:
NCT01729091
Conditions
- Plasma Cell Leukemia
- Plasma Cell Myeloma
Interventions
Drug | Synonyms | Arms |
---|
Elotuzumab | BMS-901608, Empliciti, HuLuc-63, HuLuc63, PDL-063, PDL063 | Treatment (chemotherapy, UCB-derived NK cells, transplant) |
Lenalidomide | CC-5013, CC5013, CDC 501, Revlimid | Treatment (chemotherapy, UCB-derived NK cells, transplant) |
Melphalan | 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 | Treatment (chemotherapy, UCB-derived NK cells, transplant) |
Natural Killer Cell Therapy | | Treatment (chemotherapy, UCB-derived NK cells, transplant) |
Umbilical Cord Blood-Derived Lymphocyte Therapy | | Treatment (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
Name | Type | Description | Interventions |
---|
Treatment (chemotherapy, UCB-derived NK cells, transplant) | Experimental | 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. | - 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
July 14, 2021