Trial Outcomes & Findings for Lenalidomide + Azacitidine for Adaptive Immunotherapy -> Auto SCT in Multiple Myeloma (NCT NCT01050790)

NCT ID: NCT01050790

Last Updated: 2018-06-26

Results Overview

Time frame is post 2nd and 3rd cycles of rev/aza and after stem cell transplant engraftment.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 17 participants
• Primary outcome timeframe: 6 months
• Results posted on: 2018-06-26

Participant Flow

Potential patients will be identified at the first BMT consult. They will then be preliminarily screened. If deemed eligible, they will be consented at the second BMT consult. After consent the subject will be officially screened for eligibility as described in the protocol. If eligible they will be enrolled.

Participant milestones

Measure	Aza Len Lymphapheresis SCT ALI Azacitidine will be administered to all the patients subcutaneously at a dose of 75 mg/m2 daily for five days(day 1-5). These cycles will be repeated at 28 day intervals depending on hematopoietic recovery. Starting on day 6 patients will receive lenalidomide 15 mg PO daily until day 21. No drug will be administered from day 22 to day 28. Lymphapheresis will occur after cycles 2 and 3.Patients will undergo a stem cell collection approximately two weeks after complete myeloid recovery from the third cycle of therapy. Stem Cell Transplant (SCT) will occur per transplant center protocols. Post-transplant single or tandem autologous lymphocyte infusions (ALI) will be performed no earlier than 30 days post-transplant and no later than 40 days.
Overall Study STARTED	17
Overall Study COMPLETED	16
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure

Aza Len Lymphapheresis SCT ALI Azacitidine will be administered to all the patients subcutaneously at a dose of 75 mg/m2 daily for five days(day 1-5). These cycles will be repeated at 28 day intervals depending on hematopoietic recovery. Starting on day 6 patients will receive lenalidomide 15 mg PO daily until day 21. No drug will be administered from day 22 to day 28. Lymphapheresis will occur after cycles 2 and 3.Patients will undergo a stem cell collection approximately two weeks after complete myeloid recovery from the third cycle of therapy. Stem Cell Transplant (SCT) will occur per transplant center protocols. Post-transplant single or tandem autologous lymphocyte infusions (ALI) will be performed no earlier than 30 days post-transplant and no later than 40 days.

Overall Study Adverse Event

1

Baseline Characteristics

Lenalidomide + Azacitidine for Adaptive Immunotherapy -> Auto SCT in Multiple Myeloma

Baseline characteristics by cohort

Measure	Aza Len Lymphapheresis SCT ALI n=17 Participants Azacitidine will be administered to all the patients subcutaneously at a dose of 75 mg/m2 daily for five days(day 1-5). These cycles will be repeated at 28 day intervals depending on hematopoietic recovery. Starting on day 6 patients will receive lenalidomide 15 mg PO daily until day 21. No drug will be administered from day 22 to day 28. Lymphapheresis will occur after cycles 2 and 3.Patients will undergo a stem cell collection approximately two weeks after complete myeloid recovery from the third cycle of therapy. Stem Cell Transplant (SCT) will occur per transplant center protocols. Post-transplant single or tandem autologous lymphocyte infusions (ALI) will be performed no earlier than 30 days post-transplant and no later than 40 days.
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	13 Participants n=93 Participants
Age, Categorical >=65 years	4 Participants n=93 Participants
Age, Continuous	59.59 years STANDARD_DEVIATION 7.23 • n=93 Participants
Sex: Female, Male Female	7 Participants n=93 Participants
Sex: Female, Male Male	10 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	17 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	10 Participants n=93 Participants
Race (NIH/OMB) White	7 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment United States	17 participants n=93 Participants

PRIMARY outcome

Timeframe: 6 months

Population: 17 of 17 patients were able to mobilize lymphocytes. 16 of 17 patients had lymphocytes infused post transplant. 1 patient was not able to mobilize stem cells and so did not go to transplant.

Time frame is post 2nd and 3rd cycles of rev/aza and after stem cell transplant engraftment.

Outcome measures

Measure	5-azacytidine + Lenalidomide -> Auto Stem Cell Transplant n=17 Participants azacitidine: 75 mg/sq m daily for 5 days lenalidomide: 10 mg p.o. daily, Days 6-21
Feasibility to Mobilize and Infuse Autologous Lymphocytes (ALI) After Immunomodulatory Therapy and After Stem Cell Transplant Engraftment mobilize lymphocytes	17 participants
Feasibility to Mobilize and Infuse Autologous Lymphocytes (ALI) After Immunomodulatory Therapy and After Stem Cell Transplant Engraftment lymphocytes infused post transplant	16 participants
Feasibility to Mobilize and Infuse Autologous Lymphocytes (ALI) After Immunomodulatory Therapy and After Stem Cell Transplant Engraftment not able to mobilize stem cells/no transplant	1 participants

SECONDARY outcome

Timeframe: 6 months

Population: 1 patient did not proceed to transplant.

16 of 17 patients proceeded to transplant. 6 month CR rate post transplant was 8/16 (50%).

Outcome measures

Measure	5-azacytidine + Lenalidomide -> Auto Stem Cell Transplant n=16 Participants azacitidine: 75 mg/sq m daily for 5 days lenalidomide: 10 mg p.o. daily, Days 6-21
Complete Response Rate at 6 Months	50 percentage of participants

SECONDARY outcome

Timeframe: 6 months

Time frame includes after stem cell transplant engraftment. Toxicity post ALI infusion: 1 patient grade 1 hypertension 90 min post infusion. Toxicity post Rev maintenance: 1 patient not tolerated, 1 patient dose decreased due to counts.

Outcome measures

Measure	5-azacytidine + Lenalidomide -> Auto Stem Cell Transplant n=17 Participants azacitidine: 75 mg/sq m daily for 5 days lenalidomide: 10 mg p.o. daily, Days 6-21
Toxicity as Assessed by NCI CTCAE v3.0 Toxicity post ALI infusion	1 participants
Toxicity as Assessed by NCI CTCAE v3.0 Toxicity post Rev maintenance	2 participants

SECONDARY outcome

Timeframe: 28 months

Population: Progression is collected anytime after transplant.

Time to progression post transplant: For patients not in Complete Response (CR), progressive disease requires one or more: >25% increase in the level of the serum monoclonal paraprotein(absolute increase of at least 0.5 g/dL); > 25% increase in 24-hour urinary light chain excretion(absolute increase of at least 200m/24 hours). Increase plasma cells in a bone marrow aspirate( absolute increase of at least 10%). Definite increase in the size of existing bone lesions or soft tissue plasmacytomas. Development of new bone lesions or soft tissue plasmacytomas. Development of hypercalcemia (corrected serum Ca > 11.5 mg/dL or > 2.65 mmol/L) not attributable to any other cause. All relapse categories require two consecutive assessments made any time before classification as relapse or progressive disease.

Outcome measures

Measure	5-azacytidine + Lenalidomide -> Auto Stem Cell Transplant n=17 Participants azacitidine: 75 mg/sq m daily for 5 days lenalidomide: 10 mg p.o. daily, Days 6-21
Time to Progression Post Transplant	14.9 months Interval 4.2 to 28.1

SECONDARY outcome

Timeframe: 1 year to 2 years

Population: The outcome measure data was collected up to one to two years post transplant.

Survival and event-free survival curves (any event of fatality, relapse, acute or chronic GVHD) with Kaplan-Meier curves. The incidence curve for relapse - accounting for the competing risk of fatality - is plotted with step-wise curves. The R statistical software (version 2.15) was used for all time-to-event analyses, with the survival package used for survival curves, and the cmprsk package used for all competing risk curves.

Results: The one-year survival rate is 93.3% (SE = 0.4%), and the two-year survival rate is 86.1% (SE = 0.9%).

Outcome measures

Measure	5-azacytidine + Lenalidomide -> Auto Stem Cell Transplant n=17 Participants azacitidine: 75 mg/sq m daily for 5 days lenalidomide: 10 mg p.o. daily, Days 6-21
Progression-free and Overall Survival one- year survival rate	93.3 percentage of participants Interval 92.52 to 94.08
Progression-free and Overall Survival two-year survival rate	86.1 percentage of participants Interval 84.34 to 87.86
Progression-free and Overall Survival one-year relapse rate	12.5 percentage of participants Interval 11.13 to 13.87
Progression-free and Overall Survival two-year relapse rate	19.2 percentage of participants Interval 17.04 to 21.36
Progression-free and Overall Survival one-year event free survival rate	87.5 percentage of participants Interval 86.13 to 88.87
Progression-free and Overall Survival two-year event free survival rate	67.3 percentage of participants Interval 64.16 to 70.44

SECONDARY outcome

Timeframe: 6 months

Population: Not able to obtain outcome data. The lab doing this correlative analysis lost the personnel support to process the samples.

Not able to obtain outcome data.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 3 months

Six patients tested have demonstrated CTA up-regulation in either unfractionated bone marrow (n = 4) or CD138+ cells (n = 2). CTA (CTAG1B)-specific T cell response has been observed in all three patients tested and persists following SCT.

Outcome measures

Measure	5-azacytidine + Lenalidomide -> Auto Stem Cell Transplant n=17 Participants azacitidine: 75 mg/sq m daily for 5 days lenalidomide: 10 mg p.o. daily, Days 6-21
CTA Expression Before and After Azacitidine Therapy CTA up-regulation	6 participants
CTA Expression Before and After Azacitidine Therapy CD138+ cells	2 participants
CTA Expression Before and After Azacitidine Therapy unfractionated bone marrow	4 participants
CTA Expression Before and After Azacitidine Therapy CTA (CTAG1B)-specific T cell response	3 participants

Adverse Events

5-azacytidine + Lenalidomide -> Auto Stem Cell Transplant

Serious events: 9 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Measure	5-azacytidine + Lenalidomide -> Auto Stem Cell Transplant n=17 participants at risk azacitidine: 75 mg/sq m daily for 5 days lenalidomide: 10 mg p.o. daily, Days 6-21
Musculoskeletal and connective tissue disorders Pain - Pack	5.9% 1/17 • Number of events 1 • 1 year the subject will be on study and evaluated for adverse events. Medical history and physical before treatment, Days 1, 5 and 22 of the 1st cycle and before cycles 2 and 3, before ALI. Blood for study specific tests drawn before ALI and 2, 4 and 8 weeks after and if relapse occurs. Chest x ray before ALI. Bone marrow Biopsy at baseline and after cycle 3.
Renal and urinary disorders Renal failure	5.9% 1/17 • Number of events 1 • 1 year the subject will be on study and evaluated for adverse events. Medical history and physical before treatment, Days 1, 5 and 22 of the 1st cycle and before cycles 2 and 3, before ALI. Blood for study specific tests drawn before ALI and 2, 4 and 8 weeks after and if relapse occurs. Chest x ray before ALI. Bone marrow Biopsy at baseline and after cycle 3.
Gastrointestinal disorders Pain - Abdomen NOS	5.9% 1/17 • Number of events 1 • 1 year the subject will be on study and evaluated for adverse events. Medical history and physical before treatment, Days 1, 5 and 22 of the 1st cycle and before cycles 2 and 3, before ALI. Blood for study specific tests drawn before ALI and 2, 4 and 8 weeks after and if relapse occurs. Chest x ray before ALI. Bone marrow Biopsy at baseline and after cycle 3.
Respiratory, thoracic and mediastinal disorders Pneumonitis/pulmonary infiltrates	5.9% 1/17 • Number of events 1 • 1 year the subject will be on study and evaluated for adverse events. Medical history and physical before treatment, Days 1, 5 and 22 of the 1st cycle and before cycles 2 and 3, before ALI. Blood for study specific tests drawn before ALI and 2, 4 and 8 weeks after and if relapse occurs. Chest x ray before ALI. Bone marrow Biopsy at baseline and after cycle 3.
Respiratory, thoracic and mediastinal disorders Dyspnea	11.8% 2/17 • Number of events 2 • 1 year the subject will be on study and evaluated for adverse events. Medical history and physical before treatment, Days 1, 5 and 22 of the 1st cycle and before cycles 2 and 3, before ALI. Blood for study specific tests drawn before ALI and 2, 4 and 8 weeks after and if relapse occurs. Chest x ray before ALI. Bone marrow Biopsy at baseline and after cycle 3.
Psychiatric disorders Mood alteration - Anxiety	5.9% 1/17 • Number of events 1 • 1 year the subject will be on study and evaluated for adverse events. Medical history and physical before treatment, Days 1, 5 and 22 of the 1st cycle and before cycles 2 and 3, before ALI. Blood for study specific tests drawn before ALI and 2, 4 and 8 weeks after and if relapse occurs. Chest x ray before ALI. Bone marrow Biopsy at baseline and after cycle 3.
Blood and lymphatic system disorders Infection with normal ANC or Grade 1 or 2 neutrophils - blood	11.8% 2/17 • Number of events 2 • 1 year the subject will be on study and evaluated for adverse events. Medical history and physical before treatment, Days 1, 5 and 22 of the 1st cycle and before cycles 2 and 3, before ALI. Blood for study specific tests drawn before ALI and 2, 4 and 8 weeks after and if relapse occurs. Chest x ray before ALI. Bone marrow Biopsy at baseline and after cycle 3.
Cardiac disorders Hypotension	5.9% 1/17 • Number of events 2 • 1 year the subject will be on study and evaluated for adverse events. Medical history and physical before treatment, Days 1, 5 and 22 of the 1st cycle and before cycles 2 and 3, before ALI. Blood for study specific tests drawn before ALI and 2, 4 and 8 weeks after and if relapse occurs. Chest x ray before ALI. Bone marrow Biopsy at baseline and after cycle 3.
Psychiatric disorders Mental Status	5.9% 1/17 • Number of events 1 • 1 year the subject will be on study and evaluated for adverse events. Medical history and physical before treatment, Days 1, 5 and 22 of the 1st cycle and before cycles 2 and 3, before ALI. Blood for study specific tests drawn before ALI and 2, 4 and 8 weeks after and if relapse occurs. Chest x ray before ALI. Bone marrow Biopsy at baseline and after cycle 3.
Cardiac disorders Hypertension	5.9% 1/17 • Number of events 1 • 1 year the subject will be on study and evaluated for adverse events. Medical history and physical before treatment, Days 1, 5 and 22 of the 1st cycle and before cycles 2 and 3, before ALI. Blood for study specific tests drawn before ALI and 2, 4 and 8 weeks after and if relapse occurs. Chest x ray before ALI. Bone marrow Biopsy at baseline and after cycle 3.

Other adverse events

Measure	5-azacytidine + Lenalidomide -> Auto Stem Cell Transplant n=17 participants at risk azacitidine: 75 mg/sq m daily for 5 days lenalidomide: 10 mg p.o. daily, Days 6-21
Blood and lymphatic system disorders Low Hemoglobin	11.8% 2/17 • Number of events 3 • 1 year the subject will be on study and evaluated for adverse events. Medical history and physical before treatment, Days 1, 5 and 22 of the 1st cycle and before cycles 2 and 3, before ALI. Blood for study specific tests drawn before ALI and 2, 4 and 8 weeks after and if relapse occurs. Chest x ray before ALI. Bone marrow Biopsy at baseline and after cycle 3.
Blood and lymphatic system disorders Neutropenia	64.7% 11/17 • Number of events 27 • 1 year the subject will be on study and evaluated for adverse events. Medical history and physical before treatment, Days 1, 5 and 22 of the 1st cycle and before cycles 2 and 3, before ALI. Blood for study specific tests drawn before ALI and 2, 4 and 8 weeks after and if relapse occurs. Chest x ray before ALI. Bone marrow Biopsy at baseline and after cycle 3.
Blood and lymphatic system disorders Thrombocytopenia	11.8% 2/17 • Number of events 4 • 1 year the subject will be on study and evaluated for adverse events. Medical history and physical before treatment, Days 1, 5 and 22 of the 1st cycle and before cycles 2 and 3, before ALI. Blood for study specific tests drawn before ALI and 2, 4 and 8 weeks after and if relapse occurs. Chest x ray before ALI. Bone marrow Biopsy at baseline and after cycle 3.
Blood and lymphatic system disorders High Creatinine	5.9% 1/17 • Number of events 4 • 1 year the subject will be on study and evaluated for adverse events. Medical history and physical before treatment, Days 1, 5 and 22 of the 1st cycle and before cycles 2 and 3, before ALI. Blood for study specific tests drawn before ALI and 2, 4 and 8 weeks after and if relapse occurs. Chest x ray before ALI. Bone marrow Biopsy at baseline and after cycle 3.
Blood and lymphatic system disorders High AST	5.9% 1/17 • Number of events 1 • 1 year the subject will be on study and evaluated for adverse events. Medical history and physical before treatment, Days 1, 5 and 22 of the 1st cycle and before cycles 2 and 3, before ALI. Blood for study specific tests drawn before ALI and 2, 4 and 8 weeks after and if relapse occurs. Chest x ray before ALI. Bone marrow Biopsy at baseline and after cycle 3.
Blood and lymphatic system disorders High ALT	5.9% 1/17 • Number of events 1 • 1 year the subject will be on study and evaluated for adverse events. Medical history and physical before treatment, Days 1, 5 and 22 of the 1st cycle and before cycles 2 and 3, before ALI. Blood for study specific tests drawn before ALI and 2, 4 and 8 weeks after and if relapse occurs. Chest x ray before ALI. Bone marrow Biopsy at baseline and after cycle 3.

Additional Information

Amir A. Toor, MD, Associate Professor of Medicine

Virginia Commonwealth University/Massey Cancer Center

Phone: 804-828-4360

Email: atoor@mcvh-vcu.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place