Table 2 Basic characteristics of clinical trials on iron chelators in the treatment of leukemia

DFO

NCT00658411

Terminated

SGA

AL, MDS

DFO (50 mg/kg/d) for ≥2 weeks prior to HSCT.

At a median follow-up of 20 months, no patient relapsed or died. Estimated 2-year OS and PFS are both 100%. No patient developed grade III/IV acute GVHD or VOD.

DFX

NCT03659084

Recruiting

PCS

AML, MDS

DFX (10 mg/kg/d) at 6 months after allograft, for 3–6 months.

RFS (at 2 years), cumulative incidence of GVHD (at 3 months, 1 and 2 years) and toxicity of DFX (an average of 4 years).

NCT02413021

Unknown

RCT

AL

Ara-C (20 mg/m² bid, for 10 days, repeated every 30 days) with or without DFX (20 mg/kg/d)

CR or PR (at first month).

NCT02341495

Unknown

SGA

AML (age ≥ 65 years)

DFX (20 mg/kg/d) with VD3 (4000 IU/d) and Azacitidine (75 mg/m²/d) on d1–7, repeated every 28 days for 8 cycles.

CR, OS, PFS and DOR (up to 5 years).

3-AP

NCT00064090

Completed

Ph-I

AL, MDS

3-AP (105 mg/m²/d) followed by Ara-C (100–800 mg/m²/d) on days 1–5, repeated every 21 days for up to 6 courses in the absence of PD or toxicity.

Of 31 evaluable patients, 4 (13%) achieved a CR. The median DOR for responders was 36 weeks. The median OS for all patients and responders was 30.9 weeks and 12.6 weeks, respectively. DLTs included mucositis, neutropenic colitis, neuropathy and hyperbilirubinemia.

NCT00077181

Completed

Ph-I

AML, CML-AP

Ara-C (100 mg/m²/d, d1–5) and 3-AP (50/75/100 mg/m²/d, d2–5), repeated every 28 days for up to 4 courses in the absence of PD or toxicity.

The OR rate was 3/25, with a CR rate of 2/25. An elderly patient with primary refractory AML had HI. DLTs included methemoglobinemia, cerebellar toxicity, sensorimotor peripheral neuropathy and mucositis.

NCT00077558

Completed

Ph-I

AL, MPD

Group A: 3-AP (105 mg/m²/d, d1–5) followed by fludarabine (15–30 mg/m²/d, d1–5);

Group B: 3-AP (200 mg/m², d1) followed by fludarabine (15–30 mg/m²/d, d1–5); repeated every 21 days until PD or toxicity.

CR and PR occurred in group A (5/24, 21%), with CR occurring at the 2 highest fludarabine doses (2/12, 17%). No CR or PR occurred in group B. Response durations were short and ranged from 1.5 to 7 months. DLTs included fever, methemoglobinemia and metabolic acidosis.

NCT00381550

Completed

SGA

sAML, CML-BP, MPD

3-AP (105 mg/m²/d) followed by fludarabine (30 mg/m²/d) on d1–5, repeated every 21 days until PD or toxicity.

The OR rate was 49% (18/37), with a CR rate of 24% (9/37). In sAML, the OR rate and CR rate were 48 and 33%, respectively. Median OS of the entire cohort was 6.9 months, with a median OS of overall responders of 10.6 months.

CPX

NCT00990587

Completed

Ph-I

AL, CML, CLL, MDS, Hodgkin’s Disease

CPX (5–80 mg/m²/d d1–5, once daily), repeated every 21 days, or CPX (80 mg/m²/d d1–5, four times daily); repeated every 21 days for multiple cycles in the absence of PD or toxicity.

No patients achieved a CR or PR, but HI was observed in 2 patients. Disease stabilization occurred in 5 additional AML patients and 1 MDS patient. DLTs were gastrointestinal toxicities and knee pain.

EP

NCT00903422

Completed

RCT

MDS, sAML/MDS

EP (50-300 mg/d) or placebo until PD or toxicity.

No patients had a CR, but two (3%) patients in the EP group had PR. Median OS and PFS were longer in the EP group than in the placebo group (27.0 weeks vs 15.7 weeks, 8.1 weeks vs 6.6 weeks, respectively). HI was recorded in 23 (36%) EP patients and eight (24%) placebo patients. PD was recorded in 40 (63%) patients in the EP group and 22 (65%) patients in the placebo group. The incidence of drug-related adverse events of grade 3 or higher were similarly in the two groups.

NCT01890746

Completed

RCT

AML (except M3 or M7)

IC: daunorubicin (90 mg/m²/d, 60 mg/m²/d for age > 60 years, d1–3) and Ara-C (100 mg/m²/d, d1–7); with EP (200 mg/d, 100 mg/d for east Asians) or placebo until PLT ≥200 × 10⁹/L, or remission, or after 42 days from the start of IC.

The EP group and the placebo group achieved a similar OR rate (70% vs 73%), and so did the CR rate and PR rate. Median DOR was longer in the placebo group than in the EP group (not reached vs 22 months). Median OS was shorter in the EP group than in the placebo group (15.4 months vs 25.7 months), and more patients died in the EP group. The incidence of LVEF events and the frequency of AE were similar in both groups during IC. However, there was a trend for more serious AE, including fatal AE, in the EP group.

NCT03603795

Recruiting

RCT

AML (age > 60 years, except M3 or M7)

IC (daunorubicin 60 mg/m²/d d1–3; Ara-C 100 mg/m²/d d1–7 and Lomustine 200 mg/m² d1), with EP (200 mg/d, 100 mg/d for east Asians) or placebo from d11 to response evaluation or PLT > 100 × 10⁹/L (maximum to d45).

OR rate and percentage of patients with PLT > 100 × 10⁹/L (at d45), OS and RFS (at 1 year), OS (at 2, 3 and 5 years).

NCT02446145

Unknown

RC

AML (age ≥ 65 years, except M3)

Decitabine (20 mg/m²/d d1–5, repeated every 28 days) with EP or placebo (200 mg/d from d1, 100 mg/d for east Asians, and dose modification up to 300 mg/d, 50–150 mg for east Asians).

OR, OS, RFS and treatment change-free survival (up to 4 years).