NCT00006363

Phase III Randomized Study of Induction Chemotherapy With or Without MDR-Modulation With PSC-833 (NSC # 648265, IND # 41121) Followed by Cytogenetic Risk-Adapted Intensification Therapy Followed by Immunotherapy With rIL-2 (NSC # 373364, IND # 1969) vs. Observation in Previously Untreated Patients With AML < 60 Years

Completed Phase 3 Last updated 3 June 2013

What this trial tests

Phase 3 trial testing cytarabine in Adult Acute Basophilic Leukemia in 720 participants. Completed.

Timeline

1 November 2000

Primary endpoint
1 June 2005

Quick facts

Lead sponsor	National Cancer Institute (NCI)
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	720
Start date	1 November 2000
Primary completion	1 June 2005
Sites	1 location across United States

Drugs / interventions tested

• cytarabine — full drug profile →
• daunorubicin hydrochloride (daunorubicin) — full drug profile →
• etoposide
• valspodar
• filgrastim
• busulfan — full drug profile →
• autologous hematopoietic stem cell transplantation
• peripheral blood stem cell transplantation
• aldesleukin (ALDESLEUKIN) — full drug profile →
• clinical observation
• pharmacological study

Conditions studied

• Adult Acute Basophilic Leukemia — all drugs for Adult Acute Basophilic Leukemia →
• Adult Acute Eosinophilic Leukemia — all drugs for Adult Acute Eosinophilic Leukemia →
• Adult Acute Erythroid Leukemia (M6) — all drugs for Adult Acute Erythroid Leukemia (M6) →
• Adult Acute Megakaryoblastic Leukemia (M7) — all drugs for Adult Acute Megakaryoblastic Leukemia (M7) →

Sponsor

National Cancer Institute (NCI)

Who can join

Adults 15 to 59, any sex, with Adult Acute Basophilic Leukemia or Adult Acute Eosinophilic Leukemia. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Disease-free survival
  Time frame: Up to 10 years
  An unstratified logrank test for the induction treatment comparison and a stratified logrank test for the post-remission treatment comparison will be the primary statistical methods used for treatment comparisons.
• Overall survival
  Time frame: Up to 10 years
  An unstratified logrank test for the induction treatment comparison and a stratified logrank test for the post-remission treatment comparison will be the primary statistical methods used for treatment comparisons.

Sponsor's own description

Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. PSC 833 may increase the effectiveness of chemotherapy by making cancer cells more sensitive to the drugs. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Interleukin-2 may stimulate a person's white blood cells to kill cancer cells. This randomized phase III trial is studying giving combination chemotherapy together with PSC 833 followed by a peripheral stem cell transplant with or without interleukin-2 to see how well it works compared to combination chemotherapy alone followed by a peripheral stem cell transplant with or without interleukin-2 in treating patients with acute myeloid leukemia.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. P-glycoprotein inhibition using valspodar (PSC-833) does not improve outcomes for patients younger than age 60 years with newly diagnosed acute myeloid leukemia: Cancer and Leukemia Group B study 19808.
   Kolitz JE, George SL, Marcucci G, Vij R, et al · · 2010 · cited 94× · PMID 20522709 · DOI 10.1182/blood-2009-07-229492
2. Additional gene mutations may refine the 2017 European LeukemiaNet classification in adult patients with de novo acute myeloid leukemia aged <60 years.
   Eisfeld AK, Kohlschmidt J, Mims A, Nicolet D, et al · · 2020 · cited 78× · PMID 32461631 · DOI 10.1038/s41375-020-0872-3
3. Individual patient data meta-analysis of randomized trials evaluating IL-2 monotherapy as remission maintenance therapy in acute myeloid leukemia.
   Buyse M, Squifflet P, Lange BJ, Alonzo TA, et al · · 2011 · cited 60× · PMID 21518931 · DOI 10.1182/blood-2011-02-337725
4. Drug Resistance Mechanisms of Acute Myeloid Leukemia Stem Cells.
   Niu J, Peng D, Liu L. · · 2022 · cited 49× · PMID 35865470 · DOI 10.3389/fonc.2022.896426
5. Gene expression signature predicts relapse in adult patients with cytogenetically normal acute myeloid leukemia.
   Walker CJ, Mrózek K, Ozer HG, Nicolet D, et al · · 2021 · cited 28× · PMID 33683341 · DOI 10.1182/bloodadvances.2020003727
6. Mesenchymal Stem/Stromal Cells as a Vehicle for Cytokine Delivery: An Emerging Approach for Tumor Immunotherapy.
   Razeghian E, Margiana R, Margiana R, Chupradit S, et al · · 2021 · cited 20× · PMID 34513882 · DOI 10.3389/fmed.2021.721174
7. Effect of age on the pharmacokinetics of busulfan in patients undergoing hematopoietic cell transplantation; an alliance study (CALGB 10503, 19808, and 100103).
   Beumer JH, Owzar K, Lewis LD, Jiang C, et al · · 2014 · cited 15× · PMID 25163570 · DOI 10.1007/s00280-014-2571-0
8. Interleukin-2 as maintenance therapy for children and adults with acute myeloid leukaemia in first complete remission.
   Mao C, Fu XH, Yuan JQ, Yang ZY, et al · · 2015 · cited 10× · PMID 26544114 · DOI 10.1002/14651858.cd010248.pub2