Trial Outcomes & Findings for Chloroquine in Combination With VELCADE and Cyclophosphamide for Relapsed and Refractory Multiple Myeloma (NCT NCT01438177)

Last Updated: 2020-02-24

Results Overview

Response rate is defined as the percentage of patients who have a complete response (CR) or partial response (PR). Responses were assessed every two cycles of treatment, based on the criteria published by the International Myeloma Working Group (Durie, et al, 2006). Per International Myeloma Working Group response criteria: CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow PR: \> 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by \>90% or to \< 200 mg/24 h

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

11 participants

Primary outcome timeframe

Up to 2 years

Results posted on

2020-02-24

Participant Flow

From Oct. 2011 to March 2013, 11 patients were enrolled to the study from New York University Langone Medical Center.

Participant milestones

Participant milestones
Measure	Velcade+Cyclophosphamide+Chloroquine VELCADE given by intravenous push at 1.3 mg/m\^2 on days 1, 4, 8, 11, 22, 25, 29 and 32. Cyclophosphamide given at 50 mg orally twice per day on days 1-14 and 22-35. Chloroquine given at 500 mg orally daily on days 1-14 and 22-35. Each cycle is 42 days in length.
Overall Study STARTED	11
Overall Study COMPLETED	9
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Velcade+Cyclophosphamide+Chloroquine VELCADE given by intravenous push at 1.3 mg/m\^2 on days 1, 4, 8, 11, 22, 25, 29 and 32. Cyclophosphamide given at 50 mg orally twice per day on days 1-14 and 22-35. Chloroquine given at 500 mg orally daily on days 1-14 and 22-35. Each cycle is 42 days in length.
Overall Study Withdrawal by Subject	1
Overall Study Initiation of new therapy	1

Baseline Characteristics

Chloroquine in Combination With VELCADE and Cyclophosphamide for Relapsed and Refractory Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Velcade+Cyclophosphamide+Chloroquine n=11 Participants VELCADE given by intravenous push at 1.3 mg/m\^2 on days 1, 4, 8, 11, 22, 25, 29 and 32. Cyclophosphamide given at 50 mg orally twice per day on days 1-14 and 22-35. Chloroquine given at 500 mg orally daily on days 1-14 and 22-35. Each cycle is 42 days in length.
Age, Customized 45-53 years	2 participants n=5 Participants
Age, Customized 54-63 years	4 participants n=5 Participants
Age, Customized 64-73 years	4 participants n=5 Participants
Age, Customized 74-83 years	1 participants n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	11 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 2 years

Population: Evaluable patients.

Outcome measures

Outcome measures
Measure	Velcade+Cyclophosphamide+Chloroquine n=9 Participants VELCADE given by intravenous push at 1.3 mg/m\^2 on days 1, 4, 8, 11, 22, 25, 29 and 32. Cyclophosphamide given at 50 mg orally twice per day on days 1-14 and 22-35. Chloroquine given at 500 mg orally daily on days 1-14 and 22-35. Each cycle is 42 days in length.
Response Rate (CR + PR After 2 Cycles)	30 percentage of participants

SECONDARY outcome

Timeframe: Treatment period plus 30 days post-treatment

Population: Any patients who started the treatment

Adverse events reported here were at least possibly related to the protocol therapy.

Outcome measures

Outcome measures
Measure	Velcade+Cyclophosphamide+Chloroquine n=9 Participants VELCADE given by intravenous push at 1.3 mg/m\^2 on days 1, 4, 8, 11, 22, 25, 29 and 32. Cyclophosphamide given at 50 mg orally twice per day on days 1-14 and 22-35. Chloroquine given at 500 mg orally daily on days 1-14 and 22-35. Each cycle is 42 days in length.
Number of Participants With Adverse Events of Grade 3 or Higher Fatigue	2 participants
Number of Participants With Adverse Events of Grade 3 or Higher Hemoglobin	1 participants
Number of Participants With Adverse Events of Grade 3 or Higher Nasal cavity/paranasal reactions	1 participants
Number of Participants With Adverse Events of Grade 3 or Higher ANC/AGC	4 participants
Number of Participants With Adverse Events of Grade 3 or Higher Pain: pleural	1 participants
Number of Participants With Adverse Events of Grade 3 or Higher Platelets	5 participants

SECONDARY outcome

Timeframe: until clinical response (up to 2 years)

Population: Study was terminated prior to collection of this data point.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 2 years

Population: patients who have responded

Duration of response is the time from response (CR or PR) until progression of disease or relapse. Responses and progression were evaluated based on the criteria published by the International Myeloma Working Group (Durie, et al, 2006).

Outcome measures

Outcome measures
Measure	Velcade+Cyclophosphamide+Chloroquine n=9 Participants VELCADE given by intravenous push at 1.3 mg/m\^2 on days 1, 4, 8, 11, 22, 25, 29 and 32. Cyclophosphamide given at 50 mg orally twice per day on days 1-14 and 22-35. Chloroquine given at 500 mg orally daily on days 1-14 and 22-35. Each cycle is 42 days in length.
Median Duration of Response of This Regimen	4.4 months Interval 3.9 to 8.3

Adverse Events

Velcade+Cyclophosphamide+Chloroquine

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Velcade+Cyclophosphamide+Chloroquine n=11 participants at risk VELCADE given by intravenous push at 1.3 mg/m\^2 on days 1, 4, 8, 11, 22, 25, 29 and 32. Cyclophosphamide given at 50 mg orally twice per day on days 1-14 and 22-35. Chloroquine given at 500 mg orally daily on days 1-14 and 22-35. Each cycle is 42 days in length.
Respiratory, thoracic and mediastinal disorders pain: pleura	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.

Other adverse events

Other adverse events
Measure	Velcade+Cyclophosphamide+Chloroquine n=11 participants at risk VELCADE given by intravenous push at 1.3 mg/m\^2 on days 1, 4, 8, 11, 22, 25, 29 and 32. Cyclophosphamide given at 50 mg orally twice per day on days 1-14 and 22-35. Chloroquine given at 500 mg orally daily on days 1-14 and 22-35. Each cycle is 42 days in length.
Gastrointestinal disorders Anorexia	27.3% 3/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Ear and labyrinth disorders Tinnitus	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Skin and subcutaneous tissue disorders Bruising (in absence of Grade 3 or 4 thrombocytopenia)	18.2% 2/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Gastrointestinal disorders Constipation	72.7% 8/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Respiratory, thoracic and mediastinal disorders Cough	54.5% 6/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Investigations Creatinine	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Gastrointestinal disorders Dehydration	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Gastrointestinal disorders Dental: teeth	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Skin and subcutaneous tissue disorders Rash/desquamation	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Gastrointestinal disorders Diarrhea	45.5% 5/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Gastrointestinal disorders Distension/bloating, abdominal	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Nervous system disorders Dizziness	18.2% 2/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Gastrointestinal disorders Dry mouth/salivary gland (xerostomia)	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Skin and subcutaneous tissue disorders Dry skin	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	27.3% 3/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Blood and lymphatic system disorders Edema: limb	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Eye disorders Eyelid dysfunction	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
General disorders Fatigue (asthenia, lethargy, malaise)	90.9% 10/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
General disorders Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L):	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Infections and infestations Flu-like syndrome	27.3% 3/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Musculoskeletal and connective tissue disorders Fracture	18.2% 2/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Gastrointestinal disorders Heartburn/dyspepsia	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Blood and lymphatic system disorders Hemoglobin	18.2% 2/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Infections and infestations Infection - Other: ocular Hepes	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Infections and infestations Infection - Other: shingles	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils: Eye NOS	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Infections and infestations Infection with unknown ANC: Skin (cellulites)	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
General disorders Insomnia	18.2% 2/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Investigations Metabolic/Laboratory - Other: high BUN	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Nervous system disorders Mood alteration: Agitation	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Nervous system disorders Mood alteration: Depression	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Musculoskeletal and connective tissue disorders Muscle weakness, generalized or specific area (not due to neuropathy): Whole body/generalized	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Respiratory, thoracic and mediastinal disorders Nasal cavity/paranasal sinus reactions	36.4% 4/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Gastrointestinal disorders Nausea	63.6% 7/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Nervous system disorders Neuropathy: sensory	45.5% 5/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Blood and lymphatic system disorders Neutrophils/granulocytes (ANC/AGC):	45.5% 5/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Infections and infestations Opportunistic infection associated with >=Grade 2 Lymphopenia	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Gastrointestinal disorders Pain: Abdomen NOS	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Musculoskeletal and connective tissue disorders Pain: Back	54.5% 6/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Musculoskeletal and connective tissue disorders Pain: Bone	18.2% 2/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Reproductive system and breast disorders Pain: Breast	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Musculoskeletal and connective tissue disorders Pain: Chest wall	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Respiratory, thoracic and mediastinal disorders Pain: Chest/thorax NOS	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Musculoskeletal and connective tissue disorders Pain: Extremity-limb	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Musculoskeletal and connective tissue disorders Pain: Joint	18.2% 2/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Musculoskeletal and connective tissue disorders Pain: Muscle	27.3% 3/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
General disorders Pain: Pain NOS	27.3% 3/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Gastrointestinal disorders Pain: Stomach	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Reproductive system and breast disorders Pain: Testicle	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Respiratory, thoracic and mediastinal disorders Pain: Throat/pharynx/larynx	27.3% 3/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Investigations Platelets	54.5% 6/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
General disorders Sweating (diaphoresis)	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Vascular disorders Vessel injury-vein: Other NOS	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Eye disorders Vision-blurred vision	18.2% 2/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
Gastrointestinal disorders Vomiting	18.2% 2/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.
General disorders Weight loss	9.1% 1/11 • During treatment and within 30 days post-treatment All adverse events were reported regardless of attribution to protocol therapy.

Additional Information

Amitabha Mazumder, MD

Perlmutter Cancer Center

Phone: 212-731-5757

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place