Combination of Lenalidomide and Autologous Mature Dendritic Cells Pulsed With KRN7000 in Myeloma
Primary Purpose
Myeloma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Lenalidomide
Monocyte derived DCs loaded with KRN7000
Sponsored by
About this trial
This is an interventional treatment trial for Myeloma
Eligibility Criteria
Inclusion Criteria:
- Previously untreated asymptomatic multiple myeloma
- Prior therapy: Patients cannot have received prior thalidomide, lenalidomide or corticosteroids for the intent of treating their myeloma. Prior corticosteroid use for the treatment of non-malignant disorders is permitted; concurrent use should be restricted to the equivalent of prednisone 10 mg per day or less. Prior radiation therapy for the treatment of solitary plasmacytoma is permitted, but more than 3 months should have elapsed from the last day of radiation.
Measurable disease as defined by one of the following:
- Serum monoclonal protein ≥1.0 g by protein electrophoresis
- >200 mg of monoclonal protein in the urine on 24 hour electrophoresis
- Measurable soft tissue plasmacytoma.
≥10% plasma cells as measured on the bone marrow aspirate or bone marrow biopsy.
- Age ≥18 years.
- ECOG Performance status 0, 1, or 2.
- Willing to provide written informed consent.
- All study participants must be registered into the mandatory RevAssistSM program, and be willing and able to comply with the requirements of RevAssistSM.
- Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree not to father a child and agree to use a condom if his partner is of child bearing potential. See Appendix: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods.
Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin).
(b) Laboratory inclusion criteria obtained ≤ 1 month prior to registration:
- ANC ≥1500/μL
- PLT ≥100,000/μL
- Hemoglobin ≥8.0 g/dl
- Creatinine ≤2.0 mg/dL (Any elevation above normal range should not be felt to be related to myeloma)
Exclusion Criteria:
- Solitary plasmacytoma.
- Uncontrolled infection.
- Another active malignancy.
- Immediate need for chemotherapy in the opinion of the treating physician.
- New York Heart Association classification III or IV.
- Existing ≥Grade 2 neuropathy.
Any of the following:
- Pregnant women
- Nursing women
- This study involves an agent that has known genotoxic, mutagenic and teratogenic effects. Men or women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], or abstinence, etc.)
- Active systemic autoimmunity (e.g. systemic lupus erythematosus
Sites / Locations
- Yale University School of Medicine
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Active
Arm Description
10 mg/day in cohort 1, and 25 mg/day in cohort 2. LEN is administered orally in standard 21 day cycles starting one week before each DC injection and ending 14 days after each DC injection. All patients will receive a total of three cycles of LEN.
Outcomes
Primary Outcome Measures
Number of Dose Limiting Toxicities (DLTs)
Secondary Outcome Measures
Number of Natural Killer Cells(NKT)that make IFNγ in Vitro
Full Information
NCT ID
NCT00698776
First Posted
June 12, 2008
Last Updated
June 20, 2016
Sponsor
Yale University
Collaborators
Kyowa Kirin Co., Ltd., Celgene
1. Study Identification
Unique Protocol Identification Number
NCT00698776
Brief Title
Combination of Lenalidomide and Autologous Mature Dendritic Cells Pulsed With KRN7000 in Myeloma
Official Title
Phase I/II Trial of Combination of Lenalidomide (Revlimid, LEN) and Autologous Mature Dendritic Cells Pulsed With α-galactosyl Ceramide (α-GalCer; KRN7000) in Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
June 2016
Overall Recruitment Status
Completed
Study Start Date
April 2009 (undefined)
Primary Completion Date
May 2011 (Actual)
Study Completion Date
May 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University
Collaborators
Kyowa Kirin Co., Ltd., Celgene
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a single arm open label trial to test the tolerability of the combination of monocyte derived DCs loaded with KRN7000 (DC-KRN7000) and Lenalidomide (LEN) in patients with asymptomatic myeloma. Phase I component of the study will evaluate the optimal dose of LEN, with particular emphasis on safety. After an interim analysis of these data, a single dose level will be chosen for phase II component in additional patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Active
Arm Type
Experimental
Arm Description
10 mg/day in cohort 1, and 25 mg/day in cohort 2. LEN is administered orally in standard 21 day cycles starting one week before each DC injection and ending 14 days after each DC injection. All patients will receive a total of three cycles of LEN.
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Other Intervention Name(s)
Revlimid, LEN
Intervention Description
10 mg/day in cohort 1, and 25 mg/day in cohort 2. LEN is administered orally in standard 21 day cycles starting one week before each DC injection and ending 14 days after each DC injection. All patients will receive a total of three cycles of LEN.
Intervention Type
Biological
Intervention Name(s)
Monocyte derived DCs loaded with KRN7000
Other Intervention Name(s)
α-galactosyl-ceramide, α-GalCer
Intervention Description
10 million DCs injected intravenously
Primary Outcome Measure Information:
Title
Number of Dose Limiting Toxicities (DLTs)
Time Frame
upon completion of treatment
Secondary Outcome Measure Information:
Title
Number of Natural Killer Cells(NKT)that make IFNγ in Vitro
Time Frame
upon completion of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Previously untreated asymptomatic multiple myeloma
Prior therapy: Patients cannot have received prior thalidomide, lenalidomide or corticosteroids for the intent of treating their myeloma. Prior corticosteroid use for the treatment of non-malignant disorders is permitted; concurrent use should be restricted to the equivalent of prednisone 10 mg per day or less. Prior radiation therapy for the treatment of solitary plasmacytoma is permitted, but more than 3 months should have elapsed from the last day of radiation.
Measurable disease as defined by one of the following:
Serum monoclonal protein ≥1.0 g by protein electrophoresis
>200 mg of monoclonal protein in the urine on 24 hour electrophoresis
Measurable soft tissue plasmacytoma.
≥10% plasma cells as measured on the bone marrow aspirate or bone marrow biopsy.
Age ≥18 years.
ECOG Performance status 0, 1, or 2.
Willing to provide written informed consent.
All study participants must be registered into the mandatory RevAssistSM program, and be willing and able to comply with the requirements of RevAssistSM.
Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree not to father a child and agree to use a condom if his partner is of child bearing potential. See Appendix: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods.
Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin).
(b) Laboratory inclusion criteria obtained ≤ 1 month prior to registration:
ANC ≥1500/μL
PLT ≥100,000/μL
Hemoglobin ≥8.0 g/dl
Creatinine ≤2.0 mg/dL (Any elevation above normal range should not be felt to be related to myeloma)
Exclusion Criteria:
Solitary plasmacytoma.
Uncontrolled infection.
Another active malignancy.
Immediate need for chemotherapy in the opinion of the treating physician.
New York Heart Association classification III or IV.
Existing ≥Grade 2 neuropathy.
Any of the following:
Pregnant women
Nursing women
This study involves an agent that has known genotoxic, mutagenic and teratogenic effects. Men or women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], or abstinence, etc.)
Active systemic autoimmunity (e.g. systemic lupus erythematosus
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Madhav Dhodapkar, MD
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yale University School of Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
23100308
Citation
Richter J, Neparidze N, Zhang L, Nair S, Monesmith T, Sundaram R, Miesowicz F, Dhodapkar KM, Dhodapkar MV. Clinical regressions and broad immune activation following combination therapy targeting human NKT cells in myeloma. Blood. 2013 Jan 17;121(3):423-30. doi: 10.1182/blood-2012-06-435503. Epub 2012 Oct 24.
Results Reference
derived
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Combination of Lenalidomide and Autologous Mature Dendritic Cells Pulsed With KRN7000 in Myeloma
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