A Study of Lenalidomide and CC-486 With Radiation Therapy in Patients With Plasmacytoma

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT04174196

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

2.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate if the combination of CC-486 with lenalidomide and radiation therapy is a safe and effective treatment for plasmacytoma.

Condition or Disease	Intervention/Treatment	Phase
Plasmacytoma Plasmacytoma of Bone Multiple Myeloma	Drug: CC-486 Drug: Lenalidomide Radiation: Radiation Therapy	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Pilot Study Evaluating Lenalidomide and CC-486 in Combination With Radiotherapy For Patients With Plasmacytoma (LENAZART Study)

Actual Study Start Date :

Nov 19, 2019

Anticipated Primary Completion Date :

Nov 19, 2023

Anticipated Study Completion Date :

Nov 19, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Participants with Plasmacytoma Participants will have solitary bone plasmacytoma with minimal marrow involvement and participants with relapsed multiple myeloma with plasmacytomas	Drug: CC-486 Participants will be treated with CC-486 and lenalidomide for 6 cycles Drug: Lenalidomide Participants will be treated with CC-486 and lenalidomide for 6 cycles Radiation: Radiation Therapy Radiation therapy will be initiated to the plasmacytoma after cycle 2

Arm

Intervention/Treatment

Experimental: Participants with Plasmacytoma

Participants will have solitary bone plasmacytoma with minimal marrow involvement and participants with relapsed multiple myeloma with plasmacytomas

Drug: CC-486

Participants will be treated with CC-486 and lenalidomide for 6 cycles

Drug: Lenalidomide

Participants will be treated with CC-486 and lenalidomide for 6 cycles

Radiation: Radiation Therapy

Radiation therapy will be initiated to the plasmacytoma after cycle 2

Outcome Measures

Primary Outcome Measures

Measure Complete Response [At the end of Cycle 6 (each cycle is 28 days)]
Stringent complete response (sCR) will be computed by 2016 IMWG Criteria in addition to identifying no new lesions on PET at the end of 6 cycles of therapy

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Cohort 1: Must meet all the following 3 criteria:

Histologically confirmed newly diagnosed or recurrent solitary plasmacytoma/lytic lesion (recurrent solitary plasmacytomas will be considered based on treating physician discretion for cases where they clinically plan to treat with RT alone) - Minimal marrow involvement (Detectable clonal bone marrow plasma cells by multicolor flow cytometry and </= 10% clonal plasma cells in a bone marrow biopsy by immunohistochemistry, morphology, or flow cytometry)
Secretory M protein < 3 g/dL

Cohort 2: Must meet all the following criteria:

Relapsed multiple myeloma with plasmacytomas/lytic lesion appropriate for RT on imaging
Relapsed (reappearance of M-spike/serum FLC) or progressive myeloma defined by a 25% increase from nadir in M-spike or involved serum FLB on 2 separate measurements; or with bone marrow involvement by clonal plasma cells detectable by IHC or flow cytometry.
Any prior number of therapies is permitted, including prior radiation therapy
Allogeneic transplant patients are permitted

All Cohorts:

Age >/= 18 years
Surgical resection of plasmacytoma or stabilization surgery is permitted if necessary based on physician judgement
ECOG performance status of 0-1
Anticipated lifespan greater than 3 months
Able and willing to give valid written informed consent
Creatinine clearance >/=30ml/min by Cockroft-Gault method. See section below, "Dosing Regimen", regarding lenalidomide dose adjustment for calculated creatinine clearance

/= 30ml/min and <60ml/min

Serum bilirubin levels </= 1.5 times the upper limit of the normal range for the laboratory (ULN). Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis of Gilbert's syndrome
AST (SGOT) and ALT (SGPT) </= 2.5 x ULN
Women of childbearing potential should be advised to avoid becoming pregnant and must adhere to the scheduled pregnancy testing a required in the Revlimid REMS program. They must be agreeable to use acceptable methods of birth control throughout the study and for at least 6 months after the last dose:

Recommendation is for 2 effective contraceptive methods during the study and for at least 6 months after the last dose. Adequate forms of contraception are double-barrier methods (condoms with spermicidal jelly or foam and diaphragm with spermicidal jelly or foam), oral, depo provera, or injectable contraceptive, intrauterine devices, and tubal ligation.

Agree to abstain from breastfeeding during study participation and for at least 90 days after the last dose of investigational product (IP). Men should be advised to not father a child while receiving treatment with azacitidine. Male patients with female partners who are of childbearing potential: Recommendation is for the patient and partner use at least 2 effective contraceptive methods, as described above, during the study and for 3 months following the last dose of study drug.

Refrain from semen or sperm donation while taking IP and for at least 90 days after the last dose of IP.

Willing to be registered into the mandatory Revlimid REMS program, and be willing and able to comply with the requirements of the REMS program.
Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use physician's choice of anticoagulation).
Able to swallow oral medication
Hematologic criteria: Hemoglobin >/= 9 g/dL, platelets >/= 50,000 and ANC >/= 1

Exclusion Criteria:

Subjects should not enter the study if any of the following exclusion criteria are fulfilled:

Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking azacitidine).
Uncontrolled systemic fungal, bacterial or viral infection (defined as ongoing signs/symptoms related the infection without improvement despite appropriate antibiotics, antiviral therapy and/or other treatment)
History of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis), celiac disease (ie, sprue), prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect that would interfere with the absorption, distribution, metabolism or excretion of the study drug and/or predispose the subject to an increased risk of gastrointestinal toxicity
Abnormal coagulation parameters without any known etiology (PTT > 45 seconds, and/or INR > 1.5). Patients currently on therapeutic anti-coagulation treatment are exempt from these parameters.
Significant active cardiac disease within the previous 6 months including:

NYHA class 4 CHF Unstable angina Myocardial infarction

known or suspected hypersensitivity to azacitidine or mannitol
Known hypersensitivity to thalidomide or lenalidomide
The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
Active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) as determined by a positive Polymerase Chain Reaction (PCR) will be excluded. Patients who are seropositive because of HBV vaccine are eligible. Seropositive status-antibody positive patients with negative PCR on two occasions will be eligible
Concurrent systemic chemotherapy with drugs other than CC-486 and lenalidomide.
Patients on tacrolimus therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memoral Sloan Kettering Basking Ridge	Basking Ridge	New Jersey	United States	07920
2	Memoral Sloan Kettering Monmouth	Middletown	New Jersey	United States	07748
3	Memorial Sloan Kettering Bergen	Montvale	New Jersey	United States	07645
4	Memorial Sloan Kettering Cancer Center @ Commack	Commack	New York	United States	11725
5	Memoral Sloan Kettering Westchester	Harrison	New York	United States	10604
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
7	Memorial Sloan Kettering Nassau	Uniondale	New York	United States	11553