1454GCC: Anti-PD-1 (MK-3475) and IMiD (Pomalidomide) Combination Immunotherapy in Relapsed/Refractory Multiple Myeloma

Multiple Myeloma Clinical Trial

Official title:

1454GCC: Phase I/II Anti-PD-1 (MK-3475) and IMiD (Pomalidomide) Combination Immunotherapy in Relapsed/Refractory Multiple Myeloma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02289222
• Other study ID #: HP-00061522; GCC1454
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: December 30, 2014
• Est. completion date: August 7, 2017

Study information

• Verified date: November 2019
• Source: University of Maryland, Baltimore
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open label trial of Anti PD1/MD-3475, Pomalidomide and dexamethasone. The study will use standard (FDA approved) doses for both pomalidomide and dexamethasone. The experimental drug Anti PD-1 (MK 3475) given on days 1 and 14.

Description:

This phase I/II study is focused on patients with relapsed or refractory multiple myeloma. MK-3475 will be given as an intravenous infusion at every 2 weeks. Treatment will be administered on an outpatient basis.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 48
• Est. completion date: August 7, 2017
• Est. primary completion date: August 7, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Confirmed diagnosis of relapsed and/or refractory MM according to International Myeloma Working Group guidelines (2003)

2. Received two lines of prior therapy that includes an IMiD (lenalidomide or thalidomide) and a proteasome inhibitor (bortezomib and/or carfilzomib) (used either separately or in combination). (a). Prior pomalidomide therapy is permitted, provided the patient achieved at least a partial remission and had not progressed for 3 months after stopping therapy.

3. Measureable disease as defined by the protocol (assessed within 28 days prior to registration).

4. Be willing and able to provide written informed consent/assent for the trial.

5. Be over 18 years of age on day of signing informed consent.

6. Have a performance status of 2 on the ECOG Performance Scale.

7. Demonstrate adequate organ function as defined by the protocol.

8. Female subject of childbearing potential should have a negative serum pregnancy within 72 hours prior to receiving the first dose of study drug.

9. Male subjects should agree to use an adequate method of contraception.

Exclusion Criteria:

1. Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.

2. Has a diagnosis of immunodeficiency (HIV) or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.

3. Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.

4. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to a previously administered agent. (Subjects with = Grade 2 neuropathy are an exception to this criterion and may qualify for the study.)

5. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or situ cervical cancer that has undergone potentially curative therapy.

6. Has known active central nervous system disease and/or carcinomatous meningitis.

7. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents.

8. Has evidence of interstitial lung disease or active, non-infectious pneumonitis.

9. Has an active infection requiring systemic therapy.

10. Has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

11. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

12. Pregnant or breastfeeding, or expecting to conceive or father children during study participation.

13. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody as per the protocol.

14. has known active Hepatitis B or Hepatitis C.

15. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)

16. Has received a live vaccine within 30 days prior to the first dose of trial treatment.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• MK-3475
Anti PD-1 (MD 3475) will be given as an intravenous infusion at 200 mg every 2 weeks.
• Pomalidomide
Pomalidomide is given at standard dose of 4 mg daily orally for 21 days
• Dexamethasone
Dexamethasone is given at 40 mg orally weekly

Locations

Country	Name	City	State
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Ashraf Badros	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Number of Participants With Adverse Events	Establish the safety and tolerability of Pomalidomide and Dexamethasone in combination with MK-3475	24 month
Secondary	PD-LI Expression On Myeloma Cells	The identification of a biomarker for response by evaluating PD-1/PDL-1 expression in patients' bone marrow aspirate samples will be analyzed in order to help select patients for future anti-PD-1 therapy. The main exploratory biomarker analysis was to examine potential correlation between expression of PD-1 on T cells and PD-L1 on myeloma cells with clinical outcome using the following parameters: response rate focusing on responses = very good partial response (VGPR) and PFS. SAS software (v.9.4; SAS Institute, Inc, Cary, NC) was used for statistical analyses.	Tissue sample collection will take place before starting study therapy with MK-3475 at baseline and again at time of relapse as defined by the International Myeloma Working Group Response Criteria (Average of up to 24months)
Secondary	Time to Progression Free Survival (PFS)	PFS will be measured in all participants. Survival and PFS functions were estimated using the Kaplan-Meier method. The Cox regression model was used to assess the following plausible risk factors for OS and PFS: age, isotype, number of cycles of therapy, and cytogenetic profile.	PFS assessments will take place after starting study therapy with MD-3475 and will continue until the start of a new anti-neoplastic therapy, disease progression, death, or the end of study up to an average of 24 months.