Phase I/II Study of Lenalidomide in Combination With Anti-PD-1 Monoclonal Antibody CT-011 in Patients With Relapsed/Refractory Multiple Myeloma
Overview
- Phase
- Phase 1
- Intervention
- lenalidomide
- Conditions
- Multiple Myeloma
- Sponsor
- Ohio State University Comprehensive Cancer Center
- Enrollment
- 20
- Locations
- 2
- Primary Endpoint
- MTD of pidilizumab combined with lenalidomide defined as the dose level at which no more than one of 6 patients experiences a dose-limiting toxicity (Phase I)
- Status
- Terminated
- Last Updated
- 3 years ago
Overview
Brief Summary
This phase I/II trial studies the side effects and best dose of lenalidomide and pidilizumab and to see how well they work in treating patients with multiple myeloma that has come back (relapsed) or has not responded to treatment (refractory). Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Monoclonal antibodies, such as pidilizumab, can block cancer growth by blocking the ability of cancer to grow and spread. Giving lenalidomide with pidilizumab may work better in treating relapsed or refractory multiple myeloma.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD), safety and efficacy of CT-011 (pidilizumab) in combination with lenalidomide (Revlimid) and assess efficacy in terms of overall response rate in patients with relapse/refractory multiple myeloma (MM). OUTLINE: This is a phase I, dose-escalation study followed by a phase II study but this phase did not move forward. Patients receive lenalidomide orally (PO) daily on days 1-21 and pidilizumab intravenously (IV) over 2 hours on day 3. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients have evidence of relapse or refractory disease as defined by International Myeloma Working Group (IMWG) criteria and measurable disease as defined by any of the following:
- •Serum M-protein \>= 0.5 g/dl (\>= 10 g/l)
- •Urine monoclonal protein \>= 200 mg/24h
- •Involved free light chain (FLC) level \>= 10mg/dl (\>= 100mg/l) and an abnormal serum free light chain ratio (\< 0.26, or \> 1.65)
- •Measurable biopsy proven plasmacytoma (should be measured within 28 days of initial investigational agent dosing)
- •Patients must have had at least 2 prior line of therapy
- •Patients must not have had progression of disease on lenalidomide 25 mg; stable disease on lenalidomide is permitted
- •Patient may be enrolled at any time from last line of therapy
- •Absolute neutrophil count (ANC) \> 1000/uL
- •Platelets \>= 75,000/uL, if plasma cell percentage on bone marrow biopsy aspirate or core is \> 30%, platelet eligibility requirement will be adjusted to 60,000/uL
Exclusion Criteria
- •Patients with peripheral neuropathy \> Common Terminology Criteria for Adverse Events (CTCAE) grade 2
- •Prior exposure to anti programmed cell death 1 (PD1) or anti programmed cell death 1 ligand 1 (PDL1)
- •Patients receiving concurrent corticosteroids at the time protocol therapy is initiated other than for physiologic maintenance treatment
- •History of allergic reaction (including erythema nodosum) to lenalidomide
- •Concurrent use of complementary or alternative medicines that would confound the interpretation of toxicities and antitumor activity of the study drugs
- •Patients with contraindication to thromboprophylaxis
- •Unacceptable cardiac risk factors defined by any of the following criteria: patients with congenital long QT syndrome, any history of ventricular fibrillation or torsade de pointes, bradycardia defined as heart rate (HR) \< 50 bpm, left ventricular ejection fraction \< 30%
- •Patients who have received targeted or investigational agents within 2 weeks or within 5 half-lives of the agent and active metabolites (whichever is longer) and who have not recovered from side effects of those therapies
- •Patients who have undergone major surgery =\< 2 weeks prior to starting study drug or who have not recovered from the side-effects of surgery
- •Patients with known positivity for human immunodeficiency virus (HIV), or hepatitis C; baseline testing for HIV and hepatitis C is not required
Arms & Interventions
Treatment (lenalidomide, pidilizumab)
Patients receive lenalidomide PO daily on days 1-21 and pidilizumab IV over 1-2 hours on day 3. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: lenalidomide
Treatment (lenalidomide, pidilizumab)
Patients receive lenalidomide PO daily on days 1-21 and pidilizumab IV over 1-2 hours on day 3. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: pidilizumab
Treatment (lenalidomide, pidilizumab)
Patients receive lenalidomide PO daily on days 1-21 and pidilizumab IV over 1-2 hours on day 3. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: pharmacological study
Treatment (lenalidomide, pidilizumab)
Patients receive lenalidomide PO daily on days 1-21 and pidilizumab IV over 1-2 hours on day 3. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: laboratory biomarker analysis
Outcomes
Primary Outcomes
MTD of pidilizumab combined with lenalidomide defined as the dose level at which no more than one of 6 patients experiences a dose-limiting toxicity (Phase I)
Time Frame: 28 days
Overall response rate in responding patients according to the IMWG response criteria (Phase II)
Time Frame: Up to 30 days
The proportion of responses (partial and complete) will be calculated out of all eligible patients who receive any treatment in that disease group who are included in the phase II assessment. Assuming the number of responses is binomially distributed, 95% binomial confidence intervals will also be calculated for the estimate of the proportion of responses.
Secondary Outcomes
- Time to progression(Time from start of treatment until progression or death, assessed up to 30 days)
- Overall survival (Phase II)(Time from start of treatment to the date of his or her death, assessed up to 30 days)
- Pharmacokinetic parameters of pidilizumab in combination with lenalidomide(Baseline, immediately at the end of infusion, 1, 24, 72, 168, and 336 hours, and just prior to course 2)