site feasibility questionnaire - oncocentreoncocentre.org/wp-content/uploads/cassiopeia_2014.pdf ·...

AXONAL – Site Feasibility Questionnaire Version 7 November 14th, 2014 – CONFIDENTIAL 1/8

Study of Daratumumab (JNJ-54767414 (HuMax® CD38) in Combination with

VELCADE, Thalidomide. and Dexamethasone (VTD) in the First Line Treatment of Transplant Eligible Subjects with Newly Diagnosed Multiple Myeloma

Sponsor: IFM in collaboration with HOVON and JANSSEN R&D

Study Coordinator: Pr Moreau

SITE FEASIBILITY QUESTIONNAIRE

Dear Investigator, Axonal is conducting site feasibility assessments for a registration clinical trial in First Line Treatment of Transplant Eligible Subjects with Newly Diagnosed Multiple Myeloma that is planned to start in Q1 2015 in France, Belgium and the Netherlands. We would appreciate any feedback you could provide with regard to the feasibility of conducting this trial at your institution.

Once completed, please return the form to the contact below, Before November 24th

The questionnaire can be returned either by email: [email protected]

or by fax: +33 (0)1 47 21 88 31

If you are interested in this study, don’t hesitate to send with this questionnaire your CV dated and signed.

We remain at your disposal and would you have any questions, do not hesitate to contact us by email [email protected] or by phone: +33 (0)1 56 38 27 08

Sincerely Yours

Marie-Lou Camut

International Project Manager

PLEASE FILL OUT ALL REQUESTED ITEMS USING CAPITALS ONLY

Name of the person completing the questionnaire: …………………………………………………….….…………. Function: …………………………………….………………………………………………..….………………………… Name of hospital (please in format ISO/CP code – City – Hospital name): Address: ………………………….………………………………..……………………………………..……………….. ……………………………………………………………………………………………………………………………… Phone: …………………………………………………………… Fax: …………………………………………..

E-mail: ….……………………………………………………………………………………………………………...…..

mailto:[email protected]



RATIONALE and STUDY DESIGN

Induction prior to and consolidation and maintenance following ACST is now emerging as a widely accepted treatment approach in newly diagnosed multiple myeloma patients who are deemed to be eligible for high dose therapy with autologous stem cell transplant. The clinical utility of improving the depth of response using consolidation therapy and preserving response in the long term using maintenance therapy has been demonstrated in a number of studies. However, multiple myeloma still remains incurable, and the agents currently available for long term therapy have a number of shortcomings in terms of safety and tolerability.

Strategies directed at improving and maintaining response for longer periods of time and new treatment options directed at alternative mechanisms are urgently needed for patients with multiple myeloma.

Daratumumab with its novel mechanism of action together and good profile of tolerability is ideally suited to being investigated as an adjunct to induction, consolidation and subsequent long term maintenance therapy

The target population for this study is newly diagnosed subjects with a confirmed diagnosis of symptomatic multiple myeloma and measurable disease who are suitable for high dose treatment with ASCT.

The safety profile of daratumumab to date, which does not appear to overlap with those known for approved agents, combined with its distinct MoA, suggest that the therapeutic profile of daratumumab combined with various backbone regimens may improve the treatment effect of these regimens. Additionally, daratumumab as a single agent may prolong the progression free interval for these patients.

This is a randomized, open-label, active control, parallel group, multicenter, Phase 3 study in subjects with previously untreated multiple myeloma. The planned number of subjects to be treated in this study is as follows:

1080 subjects (540/arm) for first randomization (induction)

800 subjects (400/arm) of the initial 1080 subjects will be randomized to maintenance

The study will consist of 3 phases: 1. The Screening Phase will extend up to 28 days prior to Cycle 1, Day 1. 2. The Treatment Phase will be conducted in 2 stages, as described below, and will extend from

Cycle 1 Day 1 until treatment discontinuation due to progressive disease, unacceptable toxicity, ineligibility for second randomization, or 2 years of maintenance therapy/observation.

3. The Follow-up Phase will extend from treatment discontinuation until death, loss to follow-up, withdrawal of consent, or study end, whichever occurs first.

The 2 stages in the Treatment Phase are described below:

Stage 1: Induction/ASCT/Consolidation Phase (1:1 Randomization)

Arm A: VTD induction therapy (4 cycles), followed by ASCT, followed by 2 cycles of VTD consolidation Arm B: VTD plus daratumumab induction therapy (4 cycles), followed by ASCT, followed by 2 cycles of VTD plus daratumumab consolidation The consolidation phase of treatment will begin approximately 30 days after ASCT. Response will be evaluated at Day 100 post ASCT.

Stage 2: Maintenance Phase (1:1 Re-randomization of subjects achieving at least a PR after consolidation)

Subjects with at least a PR will be randomized after determination of response at approximately Day 100 after ASCT, and will enter the Maintenance Phase upon completion of consolidation therapy. Subjects who have not achieved a response, regardless of whether they receive subsequent treatment, will be observed until disease progression or death. Arm A: Observation only until documented disease progression (limited to 2 years maximum duration) Arm B: Daratumumab monotherapy until documented disease progression (limited to 2 years maximum duration)


RATIONALE and STUDY DESIGN

Stem cell mobilization, conditioning, and transplant

Screening(-28 days)

VTD 4 cycles

VTD + Dara4 cycles

VTD2 cycles

VTD + Dara2 cycles

Observationuntil PD

Dara Q8wks until PD

(maximum of 2 years followed by

observation until PD)

Randomize #2

Randomize #1

Arm A Arm B

Induction Phase

Consolidation Phase

Maintenance Phase

Stag

e 1

Stag

e 2

Subjects with PR or better

Follow-up


STUDY POPULATION / REQUIREMENTS

Key inclusion criteria

- Subject must be 18 to 65 years of age

- Subject must have documented multiple myeloma satisfying the CRAB criteria and measurable disease as defined by:

Monoclonal plasma cells in the bone marrow ≥10% or presence of a biopsy proven plasmacytoma

Measurable disease as defined according to the usual criteria.

- Newly diagnosed subjects eligible for high dose therapy and autologous stem cell transplantation.

- ECOG 0, 1 or 2

- Subject must have pretreatment clinical laboratory values meeting the criteria defined in the protocol

during the Screening Phase.

- Each subject (or their legally acceptable representative) must sign an informed consent form (ICF)

Main exclusion criteria

- Subject has received daratumumab or other anti-CD38 therapies previously.

- Subject has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined

significance, or smoldering multiple myeloma. Monoclonal gammopathy of undetermined significance is

defined by presence of serum M-protein <3 g/dL; absence of lytic bone lesions, anemia, hypercalcemia,

and renal insufficiency related to the M-protein; and (if determined) proportion of plasma cells in the

bone marrow of 10% or less. Smoldering multiple myeloma is defined as asymptomatic multiple

myeloma with absence of related organ or tissue impairment (ROTI) end organ damage.

- Subject has a diagnosis of Waldenström’s macroglobulinemia, or other conditions in which IgM

M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions.

- Subject has prior or current systemic therapy or SCT for multiple myeloma, with the exception of an

emergency use of a short course (equivalent of dexamethasone 40 mg/day for a maximum 4 days) of

corticosteroids before treatment.

- Subject has peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the National

Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.

- Subject has had any prior or concurrent invasive malignancy (other than multiple myeloma) within

5 years of study start except adequately treated basal cell or squamous cell carcinoma of the skin,

carcinoma in situ of the cervix, localized prostate adenocarcinoma diagnosed ≥3 years and without

evidence of biochemical failure, or other cancer for which the subject has undergone potentially curative

therapy and has no evidence of that disease for ≥5 years.

**************************************


ORGANIZATION OF THE SITE

1. Do you identify any difficulties regarding these eligibility criteria? ………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………

2. How many patients 18 to 65 years of age are currently being treated for Multiple Myeloma in your center? ………………………………………………………………………………………………………………………...................................................................................................................................................

3. How many of those patients are newly diagnosed ones?

……………………………………………………………………………………………..…………………………………………………………………………………………………………………………………..

4. How many newly diagnosed Multiple Myeloma 18 to 65 years of age have been treated during the

last 12 months at your site? ……………………………………………………………………………………………..…………………………………………………………………………………………………………………………………..

5. Considering the main eligibility criteria and the study design, how many patients could be enrolled

in this study at your site during a year period? ……………………………………………………………………………………………..…………………………………………………………………………………………………………………………………..

6. Do you think the patient could remove its consent? ………………………………………………………..

7. Do you currently have any active trials at your site for the same patient population proposed in this

questionnaire? YES NO

If Yes: number of trials ………………

8. Do you currently plan to begin competing trials between May 2015 and May 2016 ?

YES NO If Yes: number of trials………………

9. Does your site have the facilities to perform in-house all specific procedures detailed in the study flowchart attached (see appendix 1)

YES NO

Comments, if any : ………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………

10. Do you have experience with a Central Laboratory

NB : The central lab results are needed for the response evaluation in order to randomize the patient. Also Pharmako Kinetic samples need to be send in centrally.

11. What type of internet access do you have? Dial-up Cable DSL

12. Please provide the operating system used in your institution (i.e., Windows XP, etc.):

…………………………………..

13. Do you have experience with electronic data capture (EDC / e-CRF)? Yes No If Yes, specify number of trials and system(s) used ……………………………………………….……………..

What is your standard turn-around for entering study data in the EDC system? ………………………


14. Do you have a computer that can be used for monitoring study data? Yes No

15. Your patients’ records are available in : paper format electronic format both

NB : Monitoring visits will be performed during the study in order to verify all data (100% SDV).

16. The evaluation of the peak by protein electrophoresis is it quantified (integration)? Yes No

If no, describe : ………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………

PHARMACY Daratumumab will be supplied. Investigator fees are also intended for the study.

17. Can you perform destruction of the investigational product on site?

Comments, if any : ………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………

Infusion bags must be:

Infusion bag (1000mL for first infusion, 500mL for subsequent infusions) made of polypropylene (PP),

polyethylene (PE) or polyolefin blend (PP+PE) containing 0.9 % Saline (NaCl) (sterile, pyrogen free).

Administration set must be:

o Polyvinyl chloride (PVC), polyurethane (PU) or polyethylene (PE)

The filter must be:

Latex-free, Polyethersulfone (PES),one injection port with 0.2 μm filter

18. Do you have the above mentioned materials available at your site? …………………………………………………………………

19. Do you have an infusion pump available to administer the daratumumab that is compatible with the above material ? ………………………………………………………………………………………………………….

20. What kind of Dexamethasone do you usually use?

……………………………………………………………………………………………………………………. 21. What kind of Thalidomide do you usually use? …………………………………………………………………………………………………………………….

Daratumumab requires a cold storage between 2°C and 8°C with strict temperature control.

22. Do you have a refrigerator with a central temperature monitoring ?

If no, can you perform a daily min-max reading during the week days ?

Comments, if any : ………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………

23. What type of freezer do you have for biological specimen storage (-20C/-80C)? …………………

Are your freezers equipped with an alarm?


24. Do you have a trained and dedicated staff who could work with you on this study? (Sub-

Investigator, Study Site Coordinator, Study Nurse…)?

Name/First Name Function Phone/ e-mail

: ……………………

: …………………………………………

: ……………………

: …………………………………………

: ……………………

: …………………………………………

: ……………………

: …………………………………………

: ……………………

: …………………………………………

: ……………………

: …………………………………………

: ……………………

: …………………………………………

: ……………………

: …………………………………………

: ……………………

: …………………………………………

: ……………………

: …………………………………………

: ……………………

: …………………………………………

: ……………………

: …………………………………………

: ……………………

: …………………………………………

: ……………………

: ………………………………………… 25. Do you consider that you have sufficient resources to conduct this study?

Yes No (please specify your needs):……………………………….…………….……

26. In your institution, is there an Internal Review Board (Ethics Committee) or an internal Scientific Committee that must review the protocol? Yes No

If Yes, what is this committee? ………………………………………………………………………

What is the average time from submission to approval? ………………………………………………

ain the reason and if changes to design would make you change your mind)

…………………………………………………………………………………………………………………………

………………………………………………………………………………………………………………………….


OTHER

27. What is the average/typical length of time from receipt of contract/budget to a fully executed contract? ……………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………….

28. Is your site interested in the study?

Definitely Yes

Unsure (please explain why): …………………………………………………………………………………

Definitely NOT interested (please expl

29. What would be your availability for a Site Selection Visit (about 2 hours) as soon as possible?

Thank you to indicate your preferences below:

Day Timetable 1 Timetable 2 Timetable 3

Please send the completed form to the Axonal Project Team either by email: [email protected] OR by fax: +33 (0)1 47 21 88 31

Thank you for your time and cooperation.



Appendix 1 – Study Flowchart

TIME AND EVENTS SCHEDULE, INDUCTION AND CONSOLIDATION PHASES

Notes

Screening Phase

Induction Treatment

(Cycles 1-4) ASCT

Consolidation Treatment

(Cycles 5-6) Day 100

post ASCT

within 28 days before

randomization D1 D28

D1

Study treatment should be initiated within 72 hours after randomization. Induction and consolidation cycles are approximately 28 days in duration. Treatment will be for a maximum of 4 induction cycles and 2 consolidation cycles. The start of each cycle may occur ±3 days of the scheduled day in order to accommodate the schedule of the site or subject. Details of ASCT will be collected as per Section 9.2.

Procedures

Informed consent ICF must be signed before any study-related procedures are performed. X

Eligibility criteria X X

Demography/Med ical History X

Height X

Chest X-ray Acceptable for screening if performed as part of SOC within 42 days before randomization X

PFT test Subjects with COPD or asthma, FEV1 should be measured X

Diagnostic block of bone marrow Sample to be sent to central laboratory X

ECOG

X X C5 X

12-lead ECG Acceptable for screening if performed as part of SOC within 42 days before randomization X

C4 X

Physical exam Including neurological exam X Symptom and disease directed exam as clinically indicated

Vital signs, weight

X Please see dosing table for details.

Blood type A wallet card with the subject’s blood type will be provided to subjects randomized to Arm B. X

Laboratory Assessments

Pregnancy test For women of childbearing potential only, within 10-14 days of first dose and

again within 24 hrs of first dose. Weekly during Cycle 1 and then monthly in women with regular menstrual cycles or every 2 weeks in women with irregular menstrual cycles

Hematology X Please see dosing table for details.

Serum chemistry X Please see dosing table for details.


Notes

Screening Phase

Induction Treatment

(Cycles 1-4) ASCT

Consolidation Treatment

(Cycles 5-6) Day 100

post ASCT

within 28 days before

randomization D1 D28

D1

Daratumumab PK/immunogenicity (Arm B only)

Each sample to be collected before (window -2 hrs) and immediately after (window +2 hrs) dara infusion. If an infusion reaction occurs, obtain unscheduled blood sample as soon as possible Sample to be sent to central laboratory.

X

Disease Evaluations: Every effort should be made to conduct disease evaluations as per schedule (window ±3 days). Refer to Section 9.2 for details on efficacy evaluations. Response

assessment for primary efficacy ednpoint should occur as close to Day 100 post-ASCT as possible (window up to Day 114 post ASCT). Serum disease evaluations (SPEP)

Sample to be sent to central laboratory. IFE and FLC when CR is suspected or maintained. FLC every cycle for subjects with light chain myeloma. Not required C1D1. X X X X

Urine disease evaluations (UPEP)

Sample to be sent to central laboratory. IFE when CR is suspected or maintained.Not required C1D1. X X X X

Flow cytometry X C4 X

Cytogenetics X X

Bone marrow aspirate/biopsy

For screening (up to 42 days before randomization) fresh biopsy preferred. If not available, obtain non-decalcified slides or FFPE block. Fresh biopsy and aspirate required to confirm CR/sCR. Samples to be sent to central laboratory X C4 X

Blood sample for MRD

After screening, obtain sample from subjects who achieve at least VGPR. X C4 X

Biomarker blood sample X

X

Quantitative Ig X C4 X

Assessment of lytic disease

Acceptable for screening if performed as part of SOC within 42 days before randomization X As clinically indicated

Extramedullary plasmacytomas

Subjects with history of plasmacytoma; acceptable for screening if performed as part of SOC within 42 days before randomization X

If applicable, by physical exam every 4 wks, by radiologic exam (if required) every 12 wks

Patient Reported Outcome

X X X X

Ongoing Subject Review

Adverse Events See Section 12 for detailed instructions. continuous from the time of signing of ICF until 30 days after last dose of last study drug

Concomitant Medications See Section 8 for detailed instructions. continuous from the time of signing of ICF until 30 days after last dose of last study drug


TIME AND EVENTS SCHEDULE, MAINTENANCE PHASE

Notes Day

100

pos

t

AS

CT

Maintenance Treatment Phase FU

1 9 17 25 33 41 49 52 57 65 73 81 89 97 105 befo

re P

D

afte

r P

D

Day 100 post -ASCT assessments do not need to be repeated if they were done within 14 days of Week 1 of the Maintenance Phase. Study treatment should be initiated within 72 hours after randomization. Week 1 corresponds to date of first daratumumab maintenance infusion for subjects in Arm B and randomization date for subjects in Arm A. The start of each cycle may occur ±3 weeks of the scheduled day, except for Week 52 and Week 105.

Procedures

Eligibility criteria X

ECOG X

12-lead ECG X As clinically indicated

Physical exam

Symptom and disease directed exam as clinically indicated

Weight

If a subject’s weight changes by more than 10% from baseline, the dose of all study drug should be re-calculated X X X X X X X X

X X X X X X X

Study Drug Administration (Arm B only, following second randomization)

Daratumumab Premedications as per Section 6.1.3 X X X X X X X X

X X X X X X X

Laboratory Assessments

Pregnancy test Arm B only X X X X X X X X X X X X X X X

Hematology Testing may be performed up to 2 days before infusion days. Results of hematology tests must be evaluated before each study drug administration. Perform at additional timepoints, as clinically indicated. To be done by local lab.

X X X X X X X X X X X X X X X

Serum chemistry X X X X X X X X X X X X X X X Daratumumab PK/Immunogenicity (Arm B only)

Sample to be sent to central laboratory. If an infusion reaction occurs, obtain unscheduled blood sample as soon as possible.

4 weeks and 8 weeks after last dose of daratumumab

Disease Evaluations: Every effort should be made to conduct disease evaluations as per schedule (window ±3 days). Refer to Section 9.2 for details on efficacy evaluations. All disease

assessments will be repeated at the end of Year 3 (Week 156). Serum disease evaluations (SPEP)

Sample to be sent to central laboratory. IFE and FLC when CR is suspected or maintained. FLC every cycle for subjects with light chain myeloma. X X X X X X X X X X X X X X X Q

8wk

Urine disease evaluations (UPEP)

Sample to be sent to central laboratory. IFE when CR is suspected or maintained. X X X X X X X X X X X X X X X Q

8wk


Notes Day

100

pos

t

AS

CT

Maintenance Treatment Phase FU

1 9 17 25 33 41 49 52 57 65 73 81 89 97 105 befo

re P

D

afte

r P

D

Flow cytometry

X X X Bone marrow aspirate/biopsy

Fresh biopsy and aspirate required to confirm CR/sCR. Samples to be sent to central laboratory X X X X

Blood sample for MRD X X X X Biomarker blood sample

X X

Quantitative Ig X X X X X

Assessment of lytic disease

As clinically indicated

Extramedullary plasmacytomas Subjects with history of plasmacytoma If applicable, by physical exam every 4 wks, by radiologic exam (if required) every 12 wks Patient Reported Outcome

X X X X X

Follow-up Assessments (after PD), every 3 months

Second primary malignancies X

PSF2 X

Anticancer Therapy X

Survival X

Ongoing Subject Review

Adverse Events See Section 12 for detailed instructions. continuous from the time of signing of ICF until 30 days after last dose of last study drug

Concomitant Medications See Section 8 for detailed instructions. continuous from the time of signing of ICF until 30 days after last dose of last study drug

Abbreviations: AE=adverse event; C=cycle; COPD=chronic obstructive pulmonary disease; CR=complete response; ECOG=Eastern Cooperative Oncology Group; D=day; Dara=daratumumab; ECG=electrocardiogram; EOT= End-of-Treatment; FEV= Forced Expiratory Volume (in 1 second); FFPE=formalin-fixed paraffin embedded; FLC=free light chain; ICF=informed consent form; MRD=minimal residual disease; MRI=magnetic resonance imaging; PBMC= peripheral blood mononuclear cell ; PK=pharmacokinetics; PD= disease progression; SAE=serious adverse event; SOC=standard of care; SPEP=serum M-protein quantitation by electrophoresis; UPEP=urine M-protein quantitation by electrophoresis; Wk=week


TIME AND EVENTS SCHEDULE: STUDY DRUG DOSING, INDUCTION AND CONSOLIDATION PHASES

Induction Phase (VTD Cycles 1-4) and Consolidation Phase (VTD Cycles 5 & 6) (28-day Cycles)

Study Day D1 D2 D3 D4 D8 D9 D10 D11 D15 D16 D21 D22 D23 D28

For study assessments, please refer to Erreur ! Source du renvoi introuvable.. Preinfusion medications -12h -1h -1h -1h -1h

Antihistamineb C1 X C1-C2 C1-C4 C1-C2

Paracetamolc X C1-C2 C1-C4 C1-C2

Study Day D1 D2 D3 D4 D8 D9 D10 D11 D15 D16 D21 D22 D23 D28

Tx. Regimen Dosing

Dexamethasoned,e X X X X X X C1-C2 C1-C2

Daratumumabf (Arm B only) X C1-C2 X C1-C2

VELCADEh X X X X

Thalidomideg ------------------------------------------------------------------------------------ (100 mg once daily)-----------------------------------------------------------------------------------------------------

Abbreviations: IV=intravenous; PO=orally; SC=subcutaneous; Tx.=treatment

a. Cycles are 4 weeks (28 days) in duration. Treatment will be for 4 x 28 day induction cycles and following ASCT 2x consolidation cycles. The start of each cycle may occur ±3 days of

the scheduled day in order to accommodate the schedule of the site or subject. The components of the treatment regimen will be administered in the following order on the days when

more than 1 component is administered: dexamethasone, daratumumab, and VELCADE.

b. Administer an antihistamine of diphenhydramine 25-50 mg, or equivalent.

c. Administer paracetamol (acetaminophen) 650-1,000 mg PO.

d. Dexamethasone (PO)

e. Dexamethasone 40mg in C1 and C2. In C3 to C6, dexamethasone 40mg on D1 and D2, dexamethasone 20mg on subsequent dosing days. On daratumumab dosing days,

dexamethasone will be administered 1 hour before the daratumumab infusion and should be given IV. Otherwise, oral dexamethasone will be administered.

f. Refer to Section Erreur ! Source du renvoi introuvable. for recommendations on the daratumumab IV infusion rate.

g. Thalidomide PO 100mg/day at bedtime.

h. Administer 1.3 mg/m2 VELCADE dose via SC injection. VELCADE doses may be delayed for up to 48 hours; however, doses must be at least 72 hours apart. Doses of VELCADE

that need to be withheld within a cycle are to be skipped and will not be made up later in the cycle.

site feasibility questionnaire - oncocentreoncocentre.org/wp-content/uploads/cassiopeia_2014.pdf ·...

Documents