| CTRI Number |
CTRI/2009/091/000207 [Registered on: 05/05/2009] |
| Last Modified On: |
13/11/2018 |
| Post Graduate Thesis |
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| Type of Trial |
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Type of Study
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| Study Design |
Single Arm Study |
Public Title of Study
Modification(s)
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This study is to evaluate the safety and tolerability of Fluphenazine HCl Monotherapy in patients with Relapsed or Relapsed and Refractory Multiple Myeloma |
Scientific Title of Study
Modification(s)
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Phase 1b Single Arm, Open Label, Multi-Center Study of Fluphenazine HCl Monotherapy in Relapsed or Relapsed and Refractory Multiple Myeloma |
| Trial Acronym |
NIL |
Secondary IDs if Any
Modification(s)
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| Secondary ID |
Identifier |
| FMCL2, Final Version dated 19-May-2008 |
Protocol Number |
| NCT00821301 |
ClinicalTrials.gov |
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)
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| Name |
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| Designation |
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| Affiliation |
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| Address |
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| Phone |
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| Fax |
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| Email |
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Details of Contact Person
Scientific Query
Modification(s)
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| Name |
Partha Chatterjee |
| Designation |
Head - Clinical Research and CTSM |
| Affiliation |
SIRO Clinpharm Pvt. Ltd. |
| Address |
SIRO Clinpharm Pvt. Ltd.
DIL Complex, II Floor, S.V. Road, Nr. Tatwagyan Vidyapeeth, Ghodbunder Road
Thane
MAHARASHTRA
400 610
India |
| Phone |
02225848000 |
| Fax |
02225848275 |
| Email |
partha.chatterjee@siroclinpharm.com |
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Details of Contact Person
Public Query
Modification(s)
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| Name |
Partha Chatterjee |
| Designation |
Head - Clinical Research and CTSM |
| Affiliation |
|
| Address |
SIRO Clinpharm Pvt. Ltd.
DIL Complex, II Floor, S.V. Road, Nr. Tatwagyan Vidyapeeth, Ghodbunder Road
Thane
MAHARASHTRA
400 610
India |
| Phone |
02225848000 |
| Fax |
02225848275 |
| Email |
partha.chatterjee@siroclinpharm.com |
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Source of Monetary or Material Support
Modification(s)
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Primary Sponsor
Modification(s)
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| Name |
Immune Control Inc |
| Address |
Four Tower Bridge200 Barr Harbor Drive,
Suite 450West Conshohocken, PA 19428
Tel: (610) 941-2971 |
| Type of Sponsor |
Pharmaceutical industry-Global |
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Details of Secondary Sponsor
Modification(s)
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Countries of Recruitment
Modification(s)
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India
United States of America |
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Sites of Study
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| No of Sites = 8 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr. T.S. Ganesan |
Amrita Institute of Medical Sciences |
,-682026
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tsganesan@aims.amrita.edu |
| Rajiv Ranjan Prasad |
Indira Gandhi Institute of Medical Sciences |
,-800014
Patna
BIHAR |
rajiv_rprasad@yahoo.com |
| Dr. Govind Babu |
Kidwai Memorial Institute of Oncology |
,-560029
Bangalore
KARNATAKA |
kgbtrials@yahoo.co.in |
| Dr. Nalini Kilara |
M.S. Ramaiah Medical College and Teaching Hospital |
,-560054
Bangalore
KARNATAKA |
nalini_kilara@yahoo.com |
| Dr.Narayanankutty Warrier |
Malabar Institute of Medical Sciences |
,-673016
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n_goray@rediffmail.com |
| Dr. Amit Bhargava |
Max Super Specialty Hospital |
,-110017
New Delhi
DELHI |
amitbharga@gmail.com |
| Dr. Ashis Mukhopadhyay |
Netaji Subhash Chandra Bose Cancer Research Institute |
,-700016
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hmcwt@dataone.in |
| Dr. V. R. Pai |
Tata Memorial Hospital |
,-400012
Mumbai
MAHARASHTRA |
drvrpai@rediffmail.com |
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Details of Ethics Committee
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| No of Ethics Committees= 8 |
| Name of Committee |
Approval Status |
| 1. Institutional Ethics Committee-Kolkata |
Approved |
| 2. Human Ethics Committee, Mumbai |
Submittted/Under Review |
| 3. Institutional Ethics Committee, Patna |
Approved |
| 4. Ethics Committee,New Delhi |
Approved |
| 5. The Medical Ethics Committee,Bangalore |
Approved |
| 6. Institutional Ethics Committee, Kochi |
Submittted/Under Review |
| 7. Ethical Review Board, Bangalore |
Approved |
| 8. Institutional Ethics Committee, Calicut |
Approved |
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Regulatory Clearance Status from DCGI
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Health Condition / Problems Studied
Modification(s)
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| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C900||Multiple myeloma, Relapsed or Relapsed-and-Refractory Multiple Myeloma, |
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Intervention / Comparator Agent
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| Type |
Name |
Details |
| Intervention |
Fluphenazine HCl |
Fluphenazine HCl will be administered intravenously. To quickly reach and maintain the target bone marrow concentration for 18 hours, the study drug will be administered using 3 bolus injections (0, 6, and 12 hours) Fluphenazine will be dose-escalated according to a modified Fibonacci scheme, terminating in 40% increments. Treatments will be administered on days 1 and 8 of every 21 day cycle.
Fluphenazine will be administered to the patients in the first cohort as 0.74mg/kg (0 hours, Bolus 1), 0.22 mg/kg ( 6 hours, Bolus 2) & 0.18 mg/kg (12 hours, Bolus 3) on days 1 & 8 of a 21 day cycle.
Subsequently for Cohort 2 Fluphenazine will be administered to the patients in the second cohort as 1.48 mg/kg (0 hours, Bolus 1), 0.44 mg/kg ( 6 hours, Bolus 2) & 0.36 mg/kg (12 hours, Bolus 3) on days 1 & 8 of a 21 day cycle.
For Cohort 3 Fluphenazine will be administered to the patients in the first cohort as 2.44mg/kg (0 hours, Bolus 1), 0.73 mg/kg ( 6 hours, Bolus 2) & 0.59 mg/kg (12 hours, Bolus 3) on days 1 & 8 of a 21 day cycle.
For Cohort 4 Fluphenazine will be administered to the patients in the first cohort as 3.71 mg/kg (0 hours, Bolus 1), 1.10 mg/kg ( 6 hours, Bolus 2) & 0.90 mg/kg (12 hours, Bolus 3) on days 1 & 8 of a 21 day cycle.
For Cohort 5 Fluphenazine will be administered to the patients in the first cohort as 5.20 mg/kg (0 hours, Bolus 1), 1.54 mg/kg ( 6 hours, Bolus 2) & 1.26 mg/kg (12 hours, Bolus 3) on days 1 & 8 of a 21 day cycle.
For Cohort 6 Fluphenazine will be administered to the patients in the first cohort as 7.28 mg/kg (0 hours, Bolus 1), 2.16 mg/kg ( 6 hours, Bolus 2) & 1.77 mg/kg (12 hours, Bolus 3) on days 1 & 8 of a 21 day cycle.
This study will be conducted in two parts. In Part 1, the MTD determining portion of the study, patients will be enrolled in cohorts of 3 patients at each dose level. At least 3 patients will complete 21 days at each dose level and will be evaluated for safety and tolerability before additional patients are treated at higher doses. Doses will be increased following a modified Fibonacci scheme.
In Part 2, twelve additional patients will be enrolled at the MTD determined in Part 1 (or the dose for the highest dose cohort completed if the MTD has not been reached) to further evaluate the safety, tolerability, and preliminary efficacy of this dose regimen.
Serum fluphenazine pharmacokinetic studies will be performed during the first cycle of the therapy in all Part 1 and Part 2 consenting patients.
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| Comparator Agent |
NIL |
NIL |
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Inclusion Criteria
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| Age From |
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| Age To |
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| Gender |
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| Details |
Inclusion Criteria:
Patients will be eligible for the study if they meet all of the following criteria:
1. Histologically or cytologically confirmed diagnosis of multiple myeloma that is relapsed or relapsed-and-refractory after at least 2 or more prior lines of therapy.
i. Patients must have achieved a best response of at least minor response (MR) to at least one prior line of therapy;
ii. Quantitative immunoglobulin levels may be substituted for M-protein levels (if not available) only for the purposes of inclusion criteria pertaining to responses/progression on past lines of therapy
2. Progressive disease, as defined in International myeloma working group uniform response criteria for multiple myeloma, must have occurred either during or subsequent to the patient?s last treatment for multiple myeloma prior to the current enrollment;
3. Measurable disease defined by serum M-protein ≥1 g/dL, or urine light chain ≥200 mg/24 hours, or abnormal serum FLC ratio with involved FLC > 10 mg/dL provided serum FLC ratio is abnormal. The serum free light chain assay is applicable only to those patients with oligosecretory myeloma who do not produce sufficient M-protein to be measurable by standard SPEP and UPEP techniques. Such oligosecretory patients may be able to qualify for study enrollment on the basis of the free light chain assay
4. Age >18 years;
5. Eastern Cooperative Oncology Group (ECOG; performance status of ≤2;
6. Life expectancy ≥12 weeks;
7. Signed written informed consent per institutional and federal regulatory requirements;
8. Did not receive chemotherapy (including systemic steroids), immunotherapy (interferon), Imids (thalidomide/lenalidomide), proteasome inhibitors (bortezomib), or radiotherapy for at least 21 days prior to Day 1 of Cycle 1;
9. Did not receive any investigational treatment for at least 28 days prior to study entry;
10. Absolute granulocyte count of ≥1,000/μL, platelet count ≥50,000/μL, and hemoglobin ≥8.0 g/dL, with no transfusion within the preceding 7 days;
11. Adequate liver function defined by a bilirubin value ≤2 times the upper limit of normal (ULN), and transaminases (AST and ALT) values ≤2.5 times ULN;
12. Adequate renal function defined by a creatinine clearance of ≥30 mL/min;
13. Adequate cardiac function defined by a left ventricular ejection fraction (LVEF) ≥40%, QTc <450 msec, and no evidence of clinically significant dysrhythmias on ECG;
14. Patient must have substantially recovered from clinically significant toxicities from prior therapies for multiple myeloma such that, in the judgment of the investigator, the residual toxicity will not likely pose an undue safety risk to the subject and will not likely confuse the interpretation of adverse events occurring in this trial.; and
15. Fertile men and women must agree to use a medically effective contraception method from signing of informed consent until 30 days after the final dose of study medication. Premenopausal women of reproductive capacity and women less than 24 months post menopause must have a negative serum pregnancy test documented prior to study entry.
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| ExclusionCriteria |
| Details |
Exclusion Criteria:
Patients meeting any of the following criteria will not be eligible for participation in the study:
1. Patients who never achieved a best response of at least minor response (MR) to at least one prior line of therapy;
2. Clinical spinal cord compression syndromes (unless patient has undergone treatment, for example, surgery or radiation therapy, and neurological findings are ≤ Grade 1 and patient is off corticosteroids for spinal cord edema or on a stable regimen of < 10 mg/day prednisone equivalent;
3. Clinical signs of brain involvement or leptomeningeal disease;
4. Plasma cell leukemia (plasma cells > 2000/cubic mm);
5. Women who are pregnant or breast feeding;
6. Other serious illness or medical condition(s) including, but not limited to the following:
i. Congestive heart failure or angina pectoris, even if medically controlled. Previous history of myocardial infarction within 1 year of study entry, uncontrolled hypertension (defined as systolic BP >160 mmHg, diastolic BP >100 mmHg), or arrhythmias,
ii. Active infection, including HIV, hepatitis B, or hepatitis C infection;
iii. History of psychosis, unless corticosteroid-induced with complete resolution following discontinuation or reduction in steroid dosing ;
iv. Subcortical brain damage; or
v. Current dialysis therapy;
7. Hypersensitivity to fluphenazine or other phenothiazines;
8. Currently being treated with hematopoietic growth factors other than erythropoietin (EPO). Treatment with hematopoietic growth factors may be started during the study with development, or worsening, of cytopenia;
9. Concurrent use of anticholinergics
10. Concurrent use of phenothiazine and atypical antipsychotics;
11. Concurrent use of anti-seizure drugs, with the exception of gabapentin for treatment of neuropathy;
12. Grade 2 or higher persisting prior treatment-related neuropathy
13. Concurrent use of systemic steroids with the exception of chronically administered steroids equivalent to ≤ 10 mg/day prednisone if patient has been on this therapy for ≥1month.
14. History of seizures or extrapyramidal symptoms; or
History of other malignancies within the past 3 years, other than adequately treated non-melanoma skin cancer, or in situ carcinoma of the cervix, unless the other malignanacy is quiescent and medical monitor approval is obtained
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Method of Generating Random Sequence
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Other |
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Method of Concealment
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Not Applicable |
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Blinding/Masking
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Open Label |
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Primary Outcome
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| Outcome |
TimePoints |
| Primary Outcomes:
Evaluate the safety and tolerability of fluphenazine when administered intravenously on days 1 and 8 of a 21 day cycle and identify the MTD and recommended dose for Phase 2 studies for this schedule of administration;
Principal Endpoints:
AEs; SAEs, discontinuation AEs, DLTs, abnormal physical findings; laboratory results; electrocardiograms
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days 1 and 8 of a 21 day cycle |
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Secondary Outcome
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| Outcome |
TimePoints |
| Secondary Outcome:
1. Evaluate the pharmacokinetics of fluphenazine in serum;
a. Principal Endpoints:
- Serum pharmacokinetic assays for fluphenazine and determination of standard pharmacokinetic parameters (serum);
2. Describe the objective response rate (ORR: sCR, CR, VGPR and PR):
a. Principal Endpoints:
- sCR, CR, VGPR and PR rates;
b. Additional Endpoint:
- MR rate
- Time to objective response
- Duration of response
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NIL |
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Target Sample Size
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Total Sample Size="0"
Sample Size from India=""
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
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Phase of Trial
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Phase 1 |
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Date of First Enrollment (India)
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Date Missing |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
30/01/2009 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
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Estimated Duration of Trial
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Years=""
Months="0"
Days="0" |
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Recruitment Status of Trial (Global)
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Other (Terminated) |
| Recruitment Status of Trial (India) |
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Publication Details
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Individual Participant Data (IPD) Sharing Statement
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Will individual participant data (IPD) be shared publicly (including data dictionaries)?
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Brief Summary
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This is a multicenter, dose-escalating, Phase 1b trial in patients with relapsed or relapsed-and-refractory multiple myeloma. Patients will be dosed on Days 1 and 8 of each 21 day cycle.
This study will be conducted in two parts. In Part 1, the MTD determining portion of the study, patients will be enrolled in cohorts of 3 patients at each dose level. At least 3 patients will complete 21 days at each dose level and will be evaluated for safety and tolerability before additional patients are treated at higher doses. Doses will be increased following a modified Fibonacci scheme.
In Part 2, twelve additional patients will be enrolled at the MTD determined in Part 1 (or the dose for the highest dose cohort completed if the MTD has not been reached) to further evaluate the safety, tolerability, and preliminary efficacy of this dose regimen.
Serum fluphenazine pharmacokinetic studies will be performed during the first cycle of the therapy in all Part 1 and Part 2 consenting patients.
The Primary Objective is to evaluate the safety and tolerability of fluphenazine when administered intravenously on days 1 and 8 of a 21 day cycle and identify the MTD and recommended dose for Phase 2 studies for this schedule of administration;
The Secondary Objectives is to evaluate the pharmacokinetics of fluphenazine in serum;
India is expected to enroll approximately 12 to 16 patients in a recruitment period of approximately 24 months.
We propose to do this study concurrently with USA sites, i.e. enrolling simultaneously at same dose levels as the American sites.
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