Trial Outcomes & Findings for Clofarabine-cyclophosphamide as Salvage Therapy for Refractory and Relapsed Acute Lymphoblastic Leukemia (ALL) Adults (NCT NCT01462253)

Last Updated: 2019-01-25

Results Overview

Disappearance of any clinical and laboratoristic sign of ALL. The patient must be transfusion-free with neutrophils \>1.0 x109/L and platelets \>100 x109/L. BM examination must show absence or reduction of blast cell content (\< 5%, none of which obviously leukemic), with cellularity in the normal or slightly hypocellular range and with evidence of trilineage hemopoiesis. BM is examined on day 28 from start of chemotherapy cycle 1, or later as clinically indicated in ill/cytopenic patients, and after cycle 2 in patients with PR proceeding to this treatment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

35 participants

Primary outcome timeframe

At day +28 from start of chemotherapy cycle 1 and after cycle 2 in pts with PR

Results posted on

2019-01-25

Participant Flow

Participant milestones

Participant milestones
Measure	Clofarabine + Cyclophosphamide Patients received a maximum of two consecutive cycles of Clofarabine-Cyclophosphamide, at an intercycle interval of 28 days or greater, according to tolerability and clinical status. Cycle 2 was only administered to patients obtaining at least a partial response (PR) after cycle 1.
Overall Study STARTED	35
Overall Study COMPLETED	27
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Clofarabine + Cyclophosphamide n=27 Participants Patients received a maximum of two consecutive cycles of Clofarabine-Cyclophosphamide, at an intercycle interval of 28 days or greater, according to tolerability and clinical status. Cycle 2 was only administered to patients obtaining at least a partial response (PR) after cycle 1.
Age, Continuous	38.7 Years n=27 Participants
Sex: Female, Male Female	12 Participants n=27 Participants
Sex: Female, Male Male	15 Participants n=27 Participants
Region of Enrollment Italy	27 participants n=27 Participants
Patient status - relapsed	25 participants n=27 Participants
Patient status - refractory	2 participants n=27 Participants
White Blood Cells (WBC)	5670.0 cells/microliter n=27 Participants
Platelets count	105000.0 cells/microliter n=27 Participants

PRIMARY outcome

Timeframe: At day +28 from start of chemotherapy cycle 1 and after cycle 2 in pts with PR

Outcome measures

Outcome measures
Measure	Clofarabine + Cyclophosphamide n=27 Participants Patients received a maximum of two consecutive cycles of Clofarabine-Cyclophosphamide, at an intercycle interval of 28 days or greater, according to tolerability and clinical status. Cycle 2 was only administered to patients obtaining at least a partial response (PR) after cycle 1.
The Primary End-point is the Number of Patients in CR After Induction Therapy.	9 Participants

SECONDARY outcome

Timeframe: At 13 months from study entry

Referring to CTCAE (Common Toxicity Criteria Events), version 4.0

Outcome measures

Outcome measures
Measure	Clofarabine + Cyclophosphamide n=27 Participants Patients received a maximum of two consecutive cycles of Clofarabine-Cyclophosphamide, at an intercycle interval of 28 days or greater, according to tolerability and clinical status. Cycle 2 was only administered to patients obtaining at least a partial response (PR) after cycle 1.
Number of Participants With Toxicity of Grade 2 or Greater	10 Participants

SECONDARY outcome

Timeframe: At week 10, 16 and 22 from start of treatment and the, every three months till study completion

Outcome measures

Outcome measures
Measure	Clofarabine + Cyclophosphamide n=10 Participants Patients received a maximum of two consecutive cycles of Clofarabine-Cyclophosphamide, at an intercycle interval of 28 days or greater, according to tolerability and clinical status. Cycle 2 was only administered to patients obtaining at least a partial response (PR) after cycle 1.
Number of Participants With Minimal Residual Disease (MRD) Response in Remission.	1 Participants

SECONDARY outcome

Timeframe: At one year from completion of chemotherapy

Population: Disease-free survival was estimated in CR patients (n=16) from date of first CR to date of death, relapse or last follow-up.

Disease-free survival (DFS) at 1 year, defined as the time interval between the evaluation of CR and relapse of the disease or death in first CR; patients still alive, in first CR, will be censored at the time of the last follow-up. In this case, the DFS curve will be truncated at 1 year

Outcome measures

Outcome measures
Measure	Clofarabine + Cyclophosphamide n=16 Participants Patients received a maximum of two consecutive cycles of Clofarabine-Cyclophosphamide, at an intercycle interval of 28 days or greater, according to tolerability and clinical status. Cycle 2 was only administered to patients obtaining at least a partial response (PR) after cycle 1.
Disease-free Survival (DFS)	31.25 Percentage of patients Interval 17.3 to 69.7

SECONDARY outcome

Timeframe: At one year from therapy completion.

Population: Overall survival was estimated from date of informed consent to date of death or last follow-up.

Overall Survival (OS) at 1 year; defined as the time interval between inclusion and death for any cause; patients still alive will be censored at the time of the last follow-up. In this case, the OS curve will be truncated at 1 year.

Outcome measures

Outcome measures
Measure	Clofarabine + Cyclophosphamide n=27 Participants Patients received a maximum of two consecutive cycles of Clofarabine-Cyclophosphamide, at an intercycle interval of 28 days or greater, according to tolerability and clinical status. Cycle 2 was only administered to patients obtaining at least a partial response (PR) after cycle 1.
Overall Survival (OS)	28.6 Percentage of patients Interval 15.3 to 53.3

SECONDARY outcome

Timeframe: At one year from therapy completion.

Population: Cumulative incidence of relapse was estimated only in CR patients (n=16) from date of first CR to date of death, relapse or last follow-up; considering death in CR as a competing risk. Median CIR not yet reached.

Cumulative incidence of relapse (CIR) at 1 year, it will be calculated from the date of achievement of the first CR, using the cumulative incidence method, considering death in CR as a competing risk. Patients still alive, without a date of relapse, will be censored at the time of the last follow-up. In this case, the CIR curve will be truncated at 1 year.

Outcome measures

Outcome measures
Measure	Clofarabine + Cyclophosphamide n=16 Participants Patients received a maximum of two consecutive cycles of Clofarabine-Cyclophosphamide, at an intercycle interval of 28 days or greater, according to tolerability and clinical status. Cycle 2 was only administered to patients obtaining at least a partial response (PR) after cycle 1.
Cumulative Incidence of Relapse (CIR)	31.25 Percentage of patients Interval 10.774 to 54.485

Adverse Events

Clofarabine + Cyclophosphamide

Serious events: 7 serious events

Other events: 12 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	Clofarabine + Cyclophosphamide n=27 participants at risk Patients received a maximum of two consecutive cycles of Clofarabine-Cyclophosphamide, at an intercycle interval of 28 days or greater, according to tolerability and clinical status. Cycle 2 was only administered to patients obtaining at least a partial response (PR) after cycle 1.
Infections and infestations Septic shock	7.4% 2/27 • Number of events 2 • 54 months from study entry
Cardiac disorders Bradycardia	3.7% 1/27 • Number of events 1 • 54 months from study entry
Cardiac disorders Atrial fibrilation	3.7% 1/27 • Number of events 2 • 54 months from study entry
Infections and infestations Pneumonitis	3.7% 1/27 • Number of events 1 • 54 months from study entry
Infections and infestations Cytomegalovirus infection	3.7% 1/27 • Number of events 1 • 54 months from study entry
Infections and infestations Klebsiella sepsis	3.7% 1/27 • Number of events 1 • 54 months from study entry
Renal and urinary disorders Acute renal failure	3.7% 1/27 • Number of events 1 • 54 months from study entry
Nervous system disorders Depressed level of consciousness	3.7% 1/27 • Number of events 1 • 54 months from study entry
Hepatobiliary disorders Hepatitis acute	3.7% 1/27 • Number of events 1 • 54 months from study entry
Injury, poisoning and procedural complications Subdural haemorrhage	3.7% 1/27 • Number of events 1 • 54 months from study entry

Other adverse events

Other adverse events
Measure	Clofarabine + Cyclophosphamide n=27 participants at risk Patients received a maximum of two consecutive cycles of Clofarabine-Cyclophosphamide, at an intercycle interval of 28 days or greater, according to tolerability and clinical status. Cycle 2 was only administered to patients obtaining at least a partial response (PR) after cycle 1.
Vascular disorders Vena cava thrombois	3.7% 1/27 • Number of events 1 • 54 months from study entry
Infections and infestations Staphylococcal infection	3.7% 1/27 • Number of events 1 • 54 months from study entry
Investigations Alanine aminotransferase increased	3.7% 1/27 • Number of events 1 • 54 months from study entry
Investigations Aspartate aminotransferase increased	3.7% 1/27 • Number of events 1 • 54 months from study entry
Investigations Blood bilirubin increased	3.7% 1/27 • Number of events 1 • 54 months from study entry
Investigations Weight decreased	3.7% 1/27 • Number of events 1 • 54 months from study entry
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.7% 1/27 • Number of events 1 • 54 months from study entry
Skin and subcutaneous tissue disorders Rash	3.7% 1/27 • Number of events 1 • 54 months from study entry
Gastrointestinal disorders Nausea	3.7% 1/27 • Number of events 1 • 54 months from study entry
Gastrointestinal disorders Vomiting	3.7% 1/27 • Number of events 1 • 54 months from study entry
General disorders Pyrexia	11.1% 3/27 • Number of events 5 • 54 months from study entry
Infections and infestations Bronchopneumonia	7.4% 2/27 • Number of events 2 • 54 months from study entry
Cardiac disorders Tachycardia	3.7% 1/27 • Number of events 1 • 54 months from study entry
General disorders Oedema	3.7% 1/27 • Number of events 1 • 54 months from study entry
Infections and infestations Bacteraemia	3.7% 1/27 • Number of events 1 • 54 months from study entry
Infections and infestations Bacterial sepsis	11.1% 3/27 • Number of events 3 • 54 months from study entry
Renal and urinary disorders Nephropathy toxic	3.7% 1/27 • Number of events 1 • 54 months from study entry
Nervous system disorders Neurological toxicity	3.7% 1/27 • Number of events 1 • 54 months from study entry
Infections and infestations Lung infection	3.7% 1/27 • Number of events 1 • 54 months from study entry
Infections and infestations Neutropenic sepsis	3.7% 1/27 • Number of events 1 • 54 months from study entry
Injury, poisoning and procedural complications Subdural haemorrhage	3.7% 1/27 • Number of events 1 • 54 months from study entry
Hepatobiliary disorders Hepatic failure	3.7% 1/27 • Number of events 1 • 54 months from study entry

Additional Information

Alfonso Piciocchi

GIMEMA

Phone: +39 06 70390513

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place