Clinical trial NCT03825146: The Effects of AMPC in the Treatments of Refractory or Relapsed AML
Official title: A Phase I Single-arm, Open-label Prospective Study to Evaluate the Efficacy and Safety of Peripheral Blood Derived Autologous Multi-lineage Potential Cells (AMPC) in Relapsed/Refractory Acute Myeloid Leukemia (AMPCAL Study)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Acute Myeloid Leukaemia Recurrent
Keywords: relapse/refractory acute myeloid leukaemia
autologous progenitor cells
Lead sponsor: Lai Corporation Pty. Ltd.
Sponsor class: INDUSTRY
First posted: 2019-01-31
Enrollment: 10
Sex: ALL
Minimum age (years): 20
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single-arm, open label, prospective study
Primary purpose: TREATMENT

Brief summary: A private trial for evaluating the overall response rate contributed by AMPC in AML in refractory or relapsed AML

Detailed description: After inclusion and exclusion criteria has been determined and approved, written informed consent will be obtained from the candidate. All medical history relevant to the diagnosis of AML will be collected.

Screening period:

The screening period could extend from 0 to 7 days depending on the completion of screening laboratory results as below.

On day -5 (up to day -1), the patient will undergo a screening test for the following test items:

* BUN, creatinine, electrolyte, liver function test (LFT)
* Full blood count (FBC), including blood smear
* Hepatitis B/C
* Human T lymphocytic virus type I and II (HTLV-I/II)
* HIV1/2
* Syphilis serology
* Mycoplasma serology For Hepatitis B/C,HTLV-I/II, HIV1/2, Syphilis serology, and Mycoplasma serology, these tests obtained up to 3 months prior to day -5 can be allowed for using as screening result.
* Chest X-ray
* Bone marrow study including aspiration with wright's stain, biopsy, flow cytometry, and chromosome study (Any molecular testing for AML is optional.).

Bone marrow biopsy can be omitted if the prior study performed within 14 days before day-5 and the available materials (core biopsy and slides) and result can be obtained for pathological review. In this case, only bone marrow aspiration for Wright's stain, flow cytometry, and chromosome study will be performed.

Bone marrow biopsy will be repeated if the previous result has been performed more than 14 days prior to day -5 and/or FBC at day -5 reveals peripheral blast count higher than 10% of total white blood cells.

For chromosome study (cytogenetics), the previous result before the recent line of chemotherapy prior to enrollment can be used for the screening data.

On day 0, peripheral blood will then be collected, ranging from 250mL to 400mL depending on candidate fitness. The blood is collected into a sterile blood bag and sealed. Subsequent processes will be conducted in the blood bag within a closed-system to minimize contamination risks. FBC will be collected in order to determine the disease status. After that, the investigator will consider to prescribe blood transfusion for the candidate.

On day 0 to day 3, the collected blood will be sent to the laboratory for stem cell culture, and a sample of the collected blood will be sent to a third-party laboratory for contamination testing of the following parameters:

* Bacterial endotoxin
* Total viable aerobic count
* Total viable count
* Microbial growth
* Mycoplasma real-time PCR test

On day 4, the biotest results will be released and the safety profiles of the AMPC product must be completed and passed before the cultured stem cells may be released for treatment

On day 5, candidates will receive an infusion of the cultured stem cells. Prior to the infusion, FBC and blood chemistry (BUN, Cr, electrolyte, LFT) will be collected and the treating doctor will first conduct an allergy skin test to determine suitability for reinfusion. The cultured stem cells are then reinfused intravenously into the candidate in a process that could take up to 2 hours

The candidate participation will take place on day 0 to day 1 or 2 (if blood transfusion is required) and day 5 (period adjusted for blood transfusion if required) for peripheral blood collection and stem cell reinfusion respectively; with 12 month follow up after treatment;

* 3 days post-treatment follow-up: full blood count test and blood smear, BUN, Cr, electrolyte, LFT
* 10 days post-treatment follow-up: full blood count test and blood smear, BUN, Cr, electrolyte, LFT
* 1 month (+/-7 days) post-treatment follow-up: full blood count test and blood smear, BUN, Cr, electrolyte, LFT, bone marrow study
* 3 month (+/-7 days) post-treatment follow-up: full blood count test and blood smear, BUN, Cr, electrolyte, LFT, bone marrow study
* 6 month (+/-7 days) post-treatment follow-up: full blood count test with bone marrow study
* 12 month (+/-7 days) post-treatment follow-up: full blood count test with bone marrow study

Eligibility criteria: Inclusion Criteria:

* Must be unequivocally diagnosed with AML according to WHO classification with accompanying bone marrow biopsy and blood panel results
* Must have refractory AML, defined as disease unresponsive to initial treatment; or relapsed AML that re-occured after treatment with conventional high dose chemotherapy
* Candidates who have no available match-sibling donor for bone marrow transplantation (BMT) or are not suitable for BMT due to any reason.
* Must have had prior treatment with chemotherapy at least 30 days prior to day 0 of this study and have recovered from treatment-related toxicity of chemotherapeutic agents with the exception of persistent diseases
* Age 20 to 60 years old

Exclusion Criteria:

* Candidates who received any investigational therapies 4 weeks prior to treatment with this protocol
* Candidates who received radiotherapy within 4 weeks prior to the treatment of this protocol
* Candidates who have not recovered from any AE caused by radiotherapy or any agents received 4 weeks earlier
* Candidates who have had a prior allogeneic stem cell transplant
* Known case of extramedullary myeloid tumor (myeloid sarcoma)
* Pregnant or breastfeeding women
* Hydroxyurea has been prescribed within 10 days prior to day-5
* Candidates have any abnormal screening laboratory results as below;

  * Hemoglobin \< 9 g/dL
  * Total white blood cells count \> 30,000/microL (without ongoing G-CSF therapy)
  * Platelet count \< 75,000/microL
  * Creatinine clearance \< 30 mL/min/1.73 m2 (by Cockcroft and Gault formula)
  * ALT \> 5x upper normal limit
  * Bone marrow study at screening period show blast \> 40% of total nucleated cells or severe hypocellularity (defined as \< 25% of normal cellularity for corresponding age) with presence of cluster of blasts
* Candidates have active heart disease including recent or chronic heart failure, unstable angina, recent acute myocardial infarction, or significant arrhythmia within 6 months of recruitment.
* Candidates have concurrent malignancies unless the candidates has been free of the disease for at least 5 years.
* Candidates positive for HIV1/2, hepatitis B/C, HTLVI/II, and Syphilis

Primary outcomes:
measure: Overall response rate (ORR) of AMPC in refractory/relapsed AML at 12 months
timeFrame: 12 months
Secondary outcomes:
measure: Safety profile and treatment-related adverse events (AE) upto 12-month follow up period
timeFrame: 12 months
measure: ORR of AMPC in refractory/relapsed AML at 3 and 6 months
timeFrame: 3 and 6 months
measure: Overall survival (OS) rate at 12 months
timeFrame: 12 months
measure: Time-to-next treatment (TTNT), defined as the time from the start of AMPC therapy to the start date of a subsequent line of therapy.
timeFrame: 12 months
Other outcomes:
Locations:
city: Samut Sakhon
country: Thailand
facility: Panacee Hospital Rama 2
Study officials:
affiliation: Panacee Hospital Rama 2
name: Supachai Ekwattanakit, Ph.D, M.D.
role: PRINCIPAL_INVESTIGATOR
References: