Lenalidomide, Dexamethasone, and Elotuzumab With or Without Cyclophosphamide in Treating Patients With Relapsed Primary Amyloidosis

• Register: ClinicalTrials.gov
• Last refreshed on: 30 January 2023
• 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: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT03252600
• 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

Contacts

• 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
[ASCT])

- 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
fibrillation

- 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 subjects who are of non-reproductive potential (i.e., post-menopausal by
history for at least 24 consecutive months; OR history of hysterectomy; OR history of
bilateral tubal ligation; OR history of bilateral oophorectomy).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 180 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) program

- 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
x ULN

- 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,
including:

- 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 psychiatri


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Recurrent Primary Amyloidosis

Intervention(s)

Drug: Cyclophosphamide

Other: Laboratory Biomarker Analysis

Biological: Elotuzumab

Drug: Dexamethasone

Other: Pharmacological Study

Drug: Lenalidomide

Primary Outcome(s)

Major hematologic response (>= very good partial response), or better [Time Frame: Up to 24 months]

Secondary Outcome(s)

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]

Complete response rate [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]

Anti-drug antibody parameters [Time Frame: Up to 24 months]

Secondary ID(s)

P30CA022453

NCI-2017-01203

2016-200

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Cancer Institute (NCI)

Multiple Myeloma Research Consortium

Bristol-Myers Squibb