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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Last refreshed on: 12 December 2020
Main ID:  NCT03252600
Date of registration: 24/07/2017
Prospective Registration: Yes
Primary sponsor: Barbara Ann Karmanos Cancer Institute
Public title: Lenalidomide, Dexamethasone, and Elotuzumab With or Without Cyclophosphamide in Treating Patients With Relapsed Primary Amyloidosis
Scientific title: A Randomized Phase 2 Trial of Lenalidomide/ Dexamethasone/ Elotuzumab +/- Cyclophosphamide Followed by Lenalidomide/ Dexamethasone/Elotuzumab Maintenance as Second-Line Therapy for Patients With Relapsed AL Amyloidosis
Date of first enrolment: August 25, 2017
Target sample size: 53
Recruitment status: Recruiting
Study type:  Interventional
Study design:  Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).  
Phase:  Phase 2
Countries of recruitment
United States
Name:     Christiane Houde
Telephone: 313-576-9381
Name:     Jeffrey Zonder, M.D.
Affiliation:  Barbara Ann Karmanos Cancer Institute
Key inclusion & exclusion criteria

Inclusion Criteria:

- Biopsy-proven histochemical diagnosis of amyloid light-chain (AL) amyloidosis based on
tissue specimens with Congo red staining or other histologic stain; thioflavin T or S,
or crystal violet; tandem mass spec or immunohistochemistry (IHC) confirmation of
immunoglobulin-derived amyloidosis is encouraged; cases in which histochemical
confirmation is lacking need to be discussed with one of the Multiple Myeloma Research
Foundation (MMRF) protocol chair/co-chairs

- One prior line of therapy (defined as either one non-transplant regimen such as
MelDex, Vel-Dex or CyBorD, one autologous stem cell transplant, or one regimen of
non-transplant induction therapy followed by a single autologous stem cell transplant
(without hematologic progression between induction and autologous stem cell transplant

- Measurable hematologic disease as defined by:

- Serum differential free light chain concentration (dFLC, difference between
amyloid forming [involved] and non-amyloid forming [uninvolved] free light chain
[FLC]) >= 50 mg/L)

- Objective measurable (cardiac, renal or liver) organ amyloid involvement defined as
follows (amyloid involvement of at least 1 required):

- Mean wall thickness > 12 mm on echocardiogram, with no other cardiac cause or an
elevated NT-ProBNP (> 332 ng/L) in the absence of renal failure or atrial

- Renal involvement is defined as proteinuria (predominantly albumin) > 0.5 g/day
in a 24-hour urine collection

- Total liver span > 15 cm in the absence of heart failure or alkaline phosphatase
> 1.5 times institutional upper limit of normal (ULN)

- NOTE: Amyloid involvement of other organ systems is allowed, but not required

- Life expectancy of >= 6 months

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2

- Female of child bearing potential (FCBP) must have a negative serum or urine pregnancy
test with a sensitivity of at least 25 mIU/mL or equivalent units of human chorionic
gonadotropin (hCG) within 10 ? 14 days prior to and again within 24 hours of starting
lenalidomide and study drug and must either commit to continue 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 through 4 weeks after the last dose of
lenalidomide and 5 half-lives after elotuzumab plus 30 days (duration of ovulatory
cycle) for a total of 120 days post-last dose of elotuzumab; FCBP must also agree to
ongoing pregnancy testing during the entire duration of treatment. Males must agree to
use a latex or synthetic condom during sexual contact with a FCBP even if they have
had a vasectomy from the time of signing the informed consent form through 28 days
after the last dose of lenalidomide and 5 half-lives of elotuzumab plus 90 days
(duration of sperm turnover) for a total of 180 days post-last dose of elotuzumab;
these same patients must not donate sperm; all patients must be counseled at a minimum
of every 28 days about pregnancy precautions and risks of fetal exposure; all patients
prior to taking lenalidomide, must be registered in and must comply with all
requirements of the lenalidomide Risk Evaluation and Mitigation Strategies (REMS)

- Ability to understand the purpose and risks of the study and provide signed and dated
informed consent and authorization to use protected health information

- Absolute neutrophil count (ANC) >= 1,000 cells/mm^3 (1.0 x 10^9/L)

- Platelet count >= 75,000 cells/mm^3 (75 x 10^9/L)

- Hemoglobin >= 8.0 g/dl (red blood cell [RBC] transfusions are permitted)

- Total bilirubin =< 1.5 x ULN (except if the patient has Gilbert?s syndrome who can
have total bilirubin =< 2 x ULN)

- Alkaline phosphatase =< 5 x ULN

- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and
alanine aminotransaminase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0

- Renal function: creatinine clearance by Cockcroft-Gault formula >= 30 mL/min

Exclusion Criteria:

- Amyloidosis due to mutations of the transthyretin gene or presence of other non-AL
amyloidosis; exception: patients with amyloid heavy (AH) or mixed AL/AH type
amyloidosis are potentially eligible

- Peripheral neuropathy >= grade 3 sensory neuropathy or >= grade 2 sensory neuropathy
with pain within 14 days of registration; prior neuropathy of this severity improved
due to medical management such as gabapentin are potentially eligible

- Cardiac stage 2 or 3 with N-terminal prohormone (NT-pro)-B-type natriuretic peptide
(BNP) > 8500 ng/L

- Medically documented cardiac syncope, uncompensated New York Heart Association (NYHA)
class 3 or 4 congestive heart failure, myocardial infarction within the previous 6
months, unstable angina pectoris, uncontrolled hypertension (defined as an average
systolic blood pressure [SBP] over 140 or a diastolic blood pressure [DBP] over 90
despite antihypertensive agents), clinically significant repetitive ventricular
arrhythmias despite antiarrhythmic treatment, or severe orthostatic hypotension or
clinically important autonomic disease; prior to study entry, any electrocardiogram
(ECG) abnormality at screening has to be documented by the investigator as not
medically relevant; NOTE: there is no lower limit of left ventricular ejection
fraction below which patients are excluded from participation

- Any medical conditions that, in the investigator?s opinion, would impose excessive
risk to the patient or would adversely affect his/her participating in this study,

- Known active infection requiring parenteral anti-infective treatment at the time of
initiation of treatment

- Other malignancy diagnosed or requiring treatment within the past 3 years with the
exception of adequately treated basal cell carcinoma, squamous cell skin cancer,
carcinoma in-situ of the cervix or breast, or low-risk Gleason grade =< 6 localized
prostate cancer not requiring therapy

- Pregnant or breast-feeding females

- Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or
confuse compliance or follow-up evaluation

- Known or active human immunodeficiency virus (HIV) infection or active hepatitis B or
C viral infect

Age minimum: 18 Years
Age maximum: N/A
Gender: All
Health Condition(s) or Problem(s) studied
Recurrent Primary Amyloidosis
Biological: Elotuzumab
Drug: Cyclophosphamide
Drug: Dexamethasone
Drug: Lenalidomide
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Primary Outcome(s)
Major hematologic response (>= very good partial response), or better [Time Frame: Up to 24 months]
Secondary Outcome(s)
Anti-drug antibody parameters [Time Frame: Up to 24 months]
Complete response rate [Time Frame: Up to 24 months]
Duration of hematologic response [Time Frame: The time from the first date a hematologic response is documented to the date of the first documented hematologic progression assessed up to 24 months]
Organ response [Time Frame: Up to 24 months]
Overall response rate [Time Frame: Up to 24 months]
Overall survival [Time Frame: Up to 24 months]
Time to hematologic progression [Time Frame: The time from the first date of first dose to the date of the first documented hematologic progression assessed up to 24 months]
Secondary ID(s)
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
Bristol-Myers Squibb
Multiple Myeloma Research Consortium
National Cancer Institute (NCI)
Ethics review
Results available:
Date Posted:
Date Completed:
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