Know Cancer

forgot password

Manipulation of L-Ascorbic Acid Level For The Treatment of Selected Cases Of Acute Myeloid Leukemia and Myelodysplastic Syndromes

Phase 2
Not Enrolling
Acute Myeloid Leukemia, Myelodysplastic Syndrome

Thank you

Trial Information

Manipulation of L-Ascorbic Acid Level For The Treatment of Selected Cases Of Acute Myeloid Leukemia and Myelodysplastic Syndromes

The seminal discovery that the in vitro growth of malignant cells could be absolutely
dependent on L-ascorbic acid (LAA) was originally published in Sciene. The cell culture
assay used with a mouse plasmacytoma model in this discovery was based on colony formation,
and was essentially the same as the one used to grow normal hemopoietic colonies, such as
CFU-GM and CFU-G, from normal bone marrow specimens. Subsequent analysis of the growth
factors for these CFUs using this same culture system eventually led to the discovery of
colony stimulating factors, such as GM-CSF and G-CSF, now widely used clinically. Human
leukemia, specifically acute myeloid leukemia (AML), cell colonies also grow well in this
culture system, as shown by extensive cell biology studies. In addition, cells from
patients with myelodysplastic syndrome (MDS), a significant proportion of them progressing
to AML behave similarly to AML cells in this culture system . In particular both AML and MDS
are identical in that the growth of colonies is enhanced by addition of LAA to the cell
culture media in a high proportion of these patients.

The large volume of in vitro data thus generated, including correlations with direct
clinical relevance is increasingly convincing that lowering of LAA levels could potentially
be developed and utilized as a treatment for specific hemopoeitic malignancies. This was
particularly attractive in view of the fact that the growth of normal hemopoietic colonies,
such as CFU-GM and CFU-G, is never enhanced by LAA. Such an absolute selectivity would
predict a lack of clinical adverse hemopoetic events from an intervention which lowered LAA
levels. We also had seemingly-contradictory data that the growth of colonies from AML and
MDS patients could be suppressed by addition of LAA, infrequently but sometimes profoundly.
However, detailed dose response analysis later clarified this: low physiologic doses enhance
and high pharmacologic doses suppress formation of leukemic colonies. From a therapeutic
perspective, we would have greater expectations for a depletion strategy than for
supplementation, because 1) leukemic suppression by addition of LAA is often accompanied by
some mild suppression of the normal CFU and therefore is not absolutely selective; and 2)
LAA supplementation has been clinically tested in a variety of solid tumors, with
controversial outcomes.

Therefore, our original protocol was developed primarily to accomplish lowering of LAA
levels, with a subsequent oral LAA supplementation used primarily to prevent scurvy and only
secondarily for possible benefit. However, with the first patient there was a strong
indication of antileukemic effects during both the LAA depletion and supplementation phases.
Based on this encouragement, the protocol was amended to formally alternate depletion with
supplementation, and to utilize intravenous (IV) administration of LAA to achieve high dose
supplementation. With 17 subsequent subjects having been treated, this study of the safety
and efficacy of cyclic manipulation of LAA levels has demonstrated beneficial outcome in a
high proportion of refractory and terminal patients with AML or MDS. Moreover, growing
laboratory evidence being produced provides a molecular basis for these clinical outcomes.

Inclusion Criteria:

- Patients should have AML or MDS according to new WHO classification, with minimum of
5% blasts in peripheral blood.

- There must be a clear and acceptable reason for not receiving standard treatments
(chemotherapy and/or stem cell transplantation); or standard treatments have already
been given and this option exhausted with evidence of refractory disease.

- Prior treatments of any forms are allowed provided there is no potential residual
beneficial effect and the patients are off treatment for at least 4 weeks, with
estimated life expectancy of at least 2 months.

- Adequate amount (4 ml) of bone marrow sent to the laboratory for cell culture

- There are no restrictions based on age, sex, or ethnicity except that adequate
contraception must be practiced in women of childbearing ages. Although AML is rare
in children, pediatric patients will be accepted.

- There is no deficiency of G6PD (RBC).

- Asymptomatic patients with disease progression and symptomatic patients.

Exclusion Criteria:


Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:


Principal Investigator

Won Seog Kim, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Samsung Medical Center


Korea: Food and Drug Administration

Study ID:




Start Date:

May 1998

Completion Date:

August 2005

Related Keywords:

  • Acute Myeloid Leukemia
  • Myelodysplastic Syndrome
  • ascorbic acid
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia