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Trial registered on ANZCTR


Registration number
ACTRN12620000271909
Ethics application status
Approved
Date submitted
17/02/2020
Date registered
2/03/2020
Date last updated
2/03/2020
Date data sharing statement initially provided
2/03/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A study assessing the impact of frailty on therapy in older people with blood cancers
Scientific title
Geriatric assessment of frailty in patients with Haematological Malignancies - A study determining the impact of frailty in older people with haematological malignancies.
Secondary ID [1] 300524 0
Nil known
Universal Trial Number (UTN)
U1111-1248-3060
Trial acronym
The GAP-HaeM Study (Geriatric assessment of frailty in patients with Haematological Malignancies)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Frailty 316219 0
Haematological malignancies 316222 0
Myelodysplastic syndrome 316226 0
Acute Myeloid Leukemia 316227 0
Multiple myeloma 316228 0
Diffuse Large B cell Lymphoma 316229 0
Quality of life 316407 0
Polypharmacy 316408 0
Condition category
Condition code
Cancer 314510 314510 0 0
Leukaemia - Acute leukaemia
Cancer 314511 314511 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 314512 314512 0 0
Myeloma
Cancer 314513 314513 0 0
Other cancer types
Blood 314514 314514 0 0
Haematological diseases
Public Health 314515 314515 0 0
Health service research

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All patients enrolled in the trial will undergo a panel of screening tools performed by a trained study member. The screening tools will be conducted face to face in the clinic setting where required and over the phone where that assessment allows. The following tools have been selected to evaluate each domain of ageing, as well as addressing important 'geriatric syndromes'. The scores reflecting impairment are listed and were selected based on either standardised cut-offs or most frequently reported cut-offs used in the literature:

1. Functional status:
-Activities of Daily Living (ADL) tool – basic functions including bathing, dressing, toileting, continence, transfers and feeding. A total score less than or equal to 5 out of 6 indicates the presence of impairment.
-Instrumental Activities of Daily Living (iADL) tool – higher functional activities including using a phone, shopping, food preparation, housekeeping, laundry, transport, medication and financial management. Scores indicative of the presence of impairments are less than or equal to 7 out of 8 for women and less than or equal to 4 out of 5 for men

2. Cognition:
-Standardised minimental state examination: score less than or equal to 24/30 indicates significant impairment. Additionally a short term recall score of less than or equal to 2/3 will be flagged as abnormal as mild cognitive deficits can progress to more severe impairment. This is will be an important longitudinal analysis with repeated testing.
-Frontal Assessment Battery: less than or equal to 12/18
The Rowland Universal Dementia Assessment Score (RUDAS) will be used for culturally and linguistically diverse persons: less than or equal to 22/30

2. Comorbidity:
-Charlson Comorbidity Index (CCI) is reflective of the burden of comorbidity which is correlated with mortality and progression free survival in the oncological setting
A score of more than or equal to 3 indicates a significantly high burden.
-Other significant comorbidities specific to this population not captured by the CCI will also be recorded and if present will be recorded as abnormal.

3. Mental health:
-Short version Geriatric Depression Scale GDS-15: A score of more than or equal to 5 out of 15 indicates the need to evaluate the patient’s mental health for possible depression
-Hospital Anxiety and Depression Scale: HAD-S >8

4. Nutrition: Mini Nutritional Assessment (MNA): A score of 17 to 23.5 indicates a risk of malnutrition and a score <17 indicates malnourishment. The threshold for an abnormal score will therefore be 23.5.

5. Mobility and frailty:
-Timed Up and Go (TUG) test which assesses dynamic mobility and balance for mobile patients: A cut off time of 13.5 seconds or more indicates a higher risk of falls and frailty
-Grip strength using a handheld dynamometer

6. Patient reported outcome measures: EORTC QLQ-C30 QOL Questionnaire. Each domain will be evaluated. Score changes of more than or equal to 10 points will be highlighted for clinical attention as these represent changes in supportive care needs.

7. The Geriatric Risk G8 screening tool

The baseline panel will be performed prior to the commencement of therapy or within 7 days of commencement of their cycle of therapy to minimize the confounding effect of therapy on the results of the tools. The screening tools are repeated at 2 to 3 monthly intervals to 12 months from enrollment in the study. The entire assessment panel from our previous experience takes 30-45 minutes. Patients with abnormal scores on at least 2 screening tools at baseline will be enrolled in the randomized arm - Stream 2. In stream 2 patients will be randomized within each condition - with Diffuse Large B Cell Lymphoma (DLBCL) and Multiple Myeloma (MM), Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) in a 1:1 fashion to either control Arm A or intervention Arm B.
Arm A: Standard of care: patients will be managed by their Haematologist in line with current protocols and procedures. There is a Nursing case coordinator at our institution for each disease stream as part of standard of care however there is no Oncogeriatric service or support. Screening assessments will be repeated during therapy as above. After the completion or cessation of therapy patients are usually followed up at 3 monthly intervals in the Haematology outpatient department as part of standard of care. Repeat assessments will occur at these standard follow-up appointments. Cross over to arm B is not permitted.
Arm B: Randomisation within each disease stream will occur to one of 2 management pathways:
• Standard of care (SOC): Patients are managed in line with current protocols/procedures
• Coordinated Multidisciplinary Case Management (CM2): This is based on the Comprehensive Geriatric Assessment model and consists of discussion at Multidisciplinary Meeting (physicians, nursing, pharmacy, allied health) where interventions will be tailored for the patient. Cases may be discussed more than once depending on their complexity and changing needs of the patient. The Multidiscplinary meeting will be scheduled for 90 minutes to discuss and document interventions.
•The patient will be reviewed by a Geriatrician or General Physician with expertise in Geriatric Medicine, to provide a sustainable model to services that do not have access to a Geriatrician. The initial consult will be face to face, lasting approximately an hour for a comprehensive review. Follow-up appointments will be determined by the clinician and in line with patient preference. Telemedicine options can also be offered to patients if appropriate.
Interventions according to deficits have been predetermined to reduce variation in clinical practice between clinicians. Interventions will be recommended in joint decision making with the patient +/- carer. If any interventions are declined this will be recorded. Additional interventions can be recommended by the physician as required and will be recorded. Interventions recommended will be followed up with monthly phone calls.

Examples of interventions according to domains:
- Chronic disease management, if CCI is more than or equal to 3: Optimisation of conditions, reconciliation with clinical practice guidelines including lifestyle modifications for example reduced salt diets and fluid restriction for heart failure, diabetic diets for diabetics. Referral for further investigation/evaluation where appropriate and necessary.
- Functional status: Refer for appropriate physical therapy program or allied health assessment (physiotherapy or exercise physiologist). Referral to support providers +/- My aged care (may need occupational therapy assessment)
- Cognitive status: Stratified according to presence of cognitive impairment. Further memory evaluation, management as indicated, carer referral to community support services including support groups for counselling and education, during hospitalisation ensuring that the ward is adherent to Delirium Clinical Care Standards and Dementia Care in Hospitals Program
- Nutritional status: Dietitian referral, dietary counselling, nutritional supplements. Speech pathology assessment or dental review may be indicated for denture fitting or dental hygiene if not already done as part of standard of care.
- Mental Health: GDS-15 >5, HAD-S >8. Further evaluation/referral either with the primary care provider (GP management plan) or specialist services if severe
- Medication reconciliation: correspondence with primary care provider and haematologist.
- Patient reported outcome measures, EORTC QLQ-C30 QOL Questionnaire – significant changes in domains or change in score of more than or equal to 10 points will prompt a review of patient’s goals and supportive care needs.

Participants in all streams will be provided with a patient diary to record hospitalizations, emergency department presentations and any other events or encounters they deem of significance. This diary will be reviewed at each scheduled visit.
Intervention code [1] 316859 0
Early detection / Screening
Intervention code [2] 316860 0
Diagnosis / Prognosis
Intervention code [3] 316861 0
Rehabilitation
Comparator / control treatment
There are 2 control groups.
Stream 1 - observational arm.
Patients with 1 or no abnormal assessments will be enrolled in Stream 1 as based on our previous experience these patients are more robust compared to those with more than 1 abnormal screening tool. In this stream patients will have standard of care in line with current protocols/procedures. Screening assessments will be repeated during therapy. After the completion or cessation of therapy patients are usually followed up at 3 monthly intervals in the Haematology outpatient department as part of standard of care. Repeat assessments will occur at these standard follow-up appointments. Crossover to stream 2 is not permitted.

Stream 2
Patients with more than 1 abnormal result on their screening tools will be enrolled in stream 2 and randomized to Arm A (control) or Arm B (intervention).
Arm A, Standard of care: patients will be managed by their Haematologist in line with current protocols and procedures. There is a Nursing case coordinator at our institution for each disease stream as part of standard of care however there is no Oncogeriatric service or support. Screening assessments will be repeated during therapy as above. After the completion or cessation of therapy patients are usually followed up at 3 monthly intervals in the Haematology outpatient department as part of standard of care. Repeat assessments will occur at these standard follow-up appointments. Cross over to arm B is not permitted.
Control group
Active

Outcomes
Primary outcome [1] 322881 0
Rate of treatment completion as planned (completing initially planned therapy course) stratified according to each condition and treatment, frailty status and intervention. Treatment completion will be determined according to the number of cycles of therapy completed accessed through medical records, in conjunction with the treating Haematologist's opinion. For example, in Myelodysplastic syndrome at least 4 to 6 cycles of azacitidine need to be completed to determine the response to treatment. If treatment is stopped due to toxicity or lack of response then it is deemed non-completion of therapy.
Timepoint [1] 322881 0
12 months from the date of enrollment
Primary outcome [2] 322882 0
Overall survival
Timepoint [2] 322882 0
12 months from the time of enrollment
Secondary outcome [1] 380127 0
Healthcare utilisation: Unscheduled admissions to hospital, presentations to emergency department, presentations to General Practitioner. These will be extracted from the patient diary, medical records for hospital encounters.
Timepoint [1] 380127 0
12 months from the time of enrollment
Secondary outcome [2] 380128 0
Quality of life: longitudinal changes from baseline and through treatment using the - EORTC QLQ-C30 QOL Questionnaire
Timepoint [2] 380128 0
12 months from time of enrollment
Secondary outcome [3] 380129 0
Changes in frailty status from baseline as a composite outcome by examining the longitudinal changes in the screening tools in each domain performed at baseline, at follow-up visits and end of study
Timepoint [3] 380129 0
12 months from the time of enrollment
Secondary outcome [4] 380130 0
Therapy modifications (delays, dose reductions, dose omissions) will be determined by reviewing medical records
Timepoint [4] 380130 0
12 months from the time of enrollment
Secondary outcome [5] 380131 0
Rate of treatment completion between patients commenced initially on dose reduced regimes versus standard dose regimes will be determined by reviewing medical records
Timepoint [5] 380131 0
12 months from the time of enrollment
Secondary outcome [6] 380468 0
Rate of haematologic versus non-haematological complications between the frail and non-frail groups will be determined by reviewing medical records
Timepoint [6] 380468 0
12 months from the time of enrollment
Secondary outcome [7] 380469 0
Rate of haematologic versus non-haematological associated mortality between the frail and non-frail groups will be determined by reviewing medical records
Timepoint [7] 380469 0
12 months from the time of enrollment

Eligibility
Key inclusion criteria
Patients must satisfy the following criteria to be enrolled in the study:
· Age 65 years or older
· Diagnosis of haematological malignancy according to relevant classification system
o Lymphoma –diffuse B-cell lymphoma (DLBCL)
o Multiple myeloma – for first line treatment or first relapse
o Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML)
· Ability to provide informed consent. If patients are from a non-english speaking background, informed consent will be determined using an interpreter and including carers
· Able to participate in study assessments
· Life expectancy predicted by the clinician to be over 6 months
· If therapy has commenced at the time of enrollment, then baseline assessments must be completed within 7 days of commencement of therapy
Minimum age
65 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
· Age <65 years of age
· MDS, AML patients previously treated with azacitidine, intensive chemotherapy and/or allogeneic stem cell transplantation
· DLBCL and multiple myeloma patients failed 2 lines of treatment
· End of life care at time of enrollment
· Best supportive care treatment at time of enrollment. Patients can be reconsented if they are then determined for active therapy and meet all other inclusion criteria.
· Enrollment on any other study where non-interventional studies are prohibited
· Any significant condition that would confound the collection or interpretation of data from the study
· Unable or unwilling to provide consent

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomization in stream 2 will occur using the randomization application in REDCap (https://projectredcap.org). Participants in Stream 2 will be stratified according to Haematological condition (DLBCL, MM, MDS, AML)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size: Based on our experience in the phase II study conducted in older MDS patients, we anticipate that approximately 20% of participants will have results within the normal range on the screening tools and that 80% will have some abnormal results. Of these 80%, half will be randomized to observation alone and half to multidisciplinary care.
Given the small number of studies in this area and the absence of literature evidence to be able to help determine a robust sample size estimation, we will collect data for approximately 6 months to evaluate the rate of recruitment, completion rates, and the prevalence of abnormalities.Currently it is estimated that approximately 170 new patients are managed at our centre with these diagnoses. Depending on the number of patients able to give consent, and the occurrence of competing trials, it should be feasible to conduct a study of sufficient power depending on the variables affecting the sample size described above.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
9/03/2020
Actual
Date of last participant enrolment
Anticipated
1/03/2021
Actual
Date of last data collection
Anticipated
1/03/2022
Actual
Sample size
Target
100
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 15889 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 29346 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 304935 0
University
Name [1] 304935 0
University of Adelaide
Country [1] 304935 0
Australia
Primary sponsor type
Individual
Name
Dr Angela Molga
Address
Department of Clinical Pharmacology, Level 8F401, Royal Adelaide Hospital, Port Road, Adelaide, SA 5000
Country
Australia
Secondary sponsor category [1] 305288 0
Individual
Name [1] 305288 0
Prof Sepher Shakib
Address [1] 305288 0
Department of Clinical Pharmacology, Level 8F401, Royal Adelaide Hospital, Port Road, Adelaide, SA 5000
Country [1] 305288 0
Australia
Secondary sponsor category [2] 305334 0
Individual
Name [2] 305334 0
Dr Gillian Caughey
Address [2] 305334 0
Registry of Senior Australians* (ROSA, Healthy Ageing Research Consortium (HARC), South Australian Health and Medical Research Institute (SAHMRI), Port Road, Adelaide, SA 5000
Country [2] 305334 0
Australia
Secondary sponsor category [3] 305335 0
Individual
Name [3] 305335 0
Dr Devendra Hiwase
Address [3] 305335 0
Department of Haematology, Royal Adelaide Hospital, Port Road, Adelaide, SA 5000
Country [3] 305335 0
Australia
Secondary sponsor category [4] 305336 0
Individual
Name [4] 305336 0
A/Prof Maria Inacio
Address [4] 305336 0
Registry of Senior Australians* (ROSA, Healthy Ageing Research Consortium (HARC), South Australian Health and Medical Research Institute (SAHMRI), Port Road, Adelaide, SA 5000
Country [4] 305336 0
Australia
Other collaborator category [1] 281195 0
Individual
Name [1] 281195 0
Dr John Maddison
Address [1] 281195 0
Northern Adelaide Geriatric Service, Modbury Hospital, Smart Road, Modbury, SA 5092
Country [1] 281195 0
Australia
Other collaborator category [2] 281196 0
Individual
Name [2] 281196 0
Dr Pratyush Giri
Address [2] 281196 0
Department of Haematology, Royal Adelaide Hospital, Port Road, Adelaide, SA 5000
Country [2] 281196 0
Australia
Other collaborator category [3] 281197 0
Individual
Name [3] 281197 0
Dr Cindy Lee
Address [3] 281197 0
Department of Haematology, Royal Adelaide Hospital, Port Road, Adelaide, SA 5000
Country [3] 281197 0
Australia
Other collaborator category [4] 281198 0
Individual
Name [4] 281198 0
Dr Danielle Blunt
Address [4] 281198 0
Department of Haematology, Royal Adelaide Hospital, Port Road, Adelaide, SA 5000
Country [4] 281198 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305344 0
Central Adelaide Local Health Network Human Research Ethics Committee (CALHN HREC)
Ethics committee address [1] 305344 0
Level 3, Roma Mitchell House, 136 North Terrace, Adelaide, SA 5000
Ethics committee country [1] 305344 0
Australia
Date submitted for ethics approval [1] 305344 0
09/11/2019
Approval date [1] 305344 0
13/12/2019
Ethics approval number [1] 305344 0
12362

Summary
Brief summary
This study is looking at how changes associated with ageing or frailty in people aged 65 years and older impacts on their ability to tolerate treatment for their blood cancer and how the therapy affects their fitness and quality of life.

Who is it for?
You may be eligible for this study if you are 65 years or older and you have been diagnosed with one of the following conditions: Myelodysplastic syndrome (MDS), Acute myeloid leukemia (AML), Multiple myeloma (MM), Diffuse-B cell Lymphoma (DLBCL), and will commence treatment either for the first time or after a first relapse.

Study details
All participants will undergo frailty screening assessments to determine eligibility to stream 1 (standard of care) or stream 2 (randomization to Arm A or Arm B). Participants will be allocated to stream 2 if they have two or more screening assessments with scores outside the normal range. Stream 1 participants will have one or no scores outside the normal range. All participants in stream 2 will be randomly allocated (50/50 chance) to Arm A or Arm B. Participants in Arm A will receive standard care from their Haematologist. Participants in Arm B will receive a tailored multidisciplinary approach to their management with specialists including a Geriatrician, Physicians, nurses, allied health and pharmacists. This visit with the specialist will take up to 1 hour for a comprehensive review. Participants in Part B will also be followed up monthly via phone calls. All participants regardless of allocation with be provided with a diary to log GP visits, emergency room encounters, unplanned admissions and any other event of significance to you.

Why is this important?
The knowledge gained from this trial will help doctors to determine the best therapy option for an individual by taking into consideration their unique ageing process and quality of life prior to commencing therapy. This will provide a more tailored approach to managing an older person's cancer.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 100070 0
Dr Angela Molga
Address 100070 0
Department of Clinical Pharmacology, Royal Adelaide Hospital, Adelaide, SA 5000
Northern Adelaide Geriatrics Service, Modbury Hospital, Smart Road, Modbury, SA 5092
Country 100070 0
Australia
Phone 100070 0
+61 08 7074 2701
Fax 100070 0
+61 08 84296070
Email 100070 0
[email protected]
Contact person for public queries
Name 100071 0
Angela Molga
Address 100071 0
Department of Clinical Pharmacology, Royal Adelaide Hospital, Adelaide, SA 5000
Northern Adelaide Geriatrics Service, Modbury Hospital, Smart Road, Modbury, SA 5092
Country 100071 0
Australia
Phone 100071 0
+61 08 7074 2701
Fax 100071 0
+61 08 84296070
Email 100071 0
[email protected]
Contact person for scientific queries
Name 100072 0
Angela Molga
Address 100072 0
Department of Clinical Pharmacology, Royal Adelaide Hospital, Adelaide, SA 5000
Northern Adelaide Geriatrics Service, Modbury Hospital, Smart Road, Modbury, SA 5092
Country 100072 0
Australia
Phone 100072 0
+61 08 7074 2701
Fax 100072 0
+61 08 84296070
Email 100072 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
6948Informed consent form  [email protected]
6949Ethical approval  [email protected] 379253-(Uploaded-17-02-2020-15-00-53)-Study-related document.pdf
7068Clinical study report  [email protected]
7069Statistical analysis plan  [email protected]
7070Study protocol  [email protected]



Results publications and other study-related documents

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