Clofarabine, Cytarabine and Mitoxantrone (CLAM) for Relapsed or Refractory AML

NCT02686593 | Completed Phase 2 DMC

• 1 other identifier: CLOFAL07200
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The study aims to evaluate the efficacy of the regimen CLAM in relapsed or refractory AML when used as first salvage for patients to relapse or fail after standard treatment with daunorubicin/cytarabine induction.

Conditions

Acute Myeloid Leukemia

Keywords

Clofarabine; Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Response rate

  Remission status will be assessed on day 28 of treatment for the assessment of response rate using standard criteria

  Day 28

Secondary Outcomes (3)

• Leukemia-free survival

  2 years

• Overall survival

  5 years

• Adverse events

  1 year

Study Arms (1)

Clofarabine, AraC, mitoxantrone (CLAM)

OTHER

This is the single arm with the intervention using Clofarabine, AraC, Mitoxantrone

Drug: Clofarabine, AraC, mitoxantrone (CLAM)

Interventions

Clofarabine, AraC, mitoxantrone (CLAM) DRUG

The combination of clofarabine, cytarabine (Ara-C) and mitoxantrone will be used in patients with AML in first relapse or after failure of first salvage

Also known as: CLAM

Clofarabine, AraC, mitoxantrone (CLAM)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Relapsed or refractory acute myeloid leukemia (AML) after one first-line chemotherapy regimen
• Patients aged 18 - 65 inclusively
• European Cooperative Oncology Group (ECOG) performance status of less than 2

You may not qualify if:

• Patients aged less than 18 or above 65
• ECOG performance status of 2 or more
• Acute promyelocytic leukaemia
• Uncontrolled active infection
• Uncontrolled arrhythmia
• Altered renal dysfunction with serum creatinine \> 1.5 x ULN and/or creatinine clearance \< 50 mL/min
• Significant neurologic (grade \> 2) or psychiatric disorder, dementia or seizures
• Clinical symptoms suggesting active central nervous system leukemia
• Severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock or disseminated intravascular coagulation
• Patients with known HIV, Hepatitis B or C infection or history of cirrhosis
• Patients Significant hepatic dysfunction: Direct bilirubin \> 1.5 x upper limit of normal (ULN) for age; ALT or AST \> 3 x upper limit of normal (ULN) for age; Lipase \> 2.0 x upper limit of normal (ULN) for age
• Females of childbearing potential must have a negative pregnancy test

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

The University of Hong Kong

Hong Kong, Hong Kong

Location

Related Publications (10)

• Faderl S, Gandhi V, Kantarjian HM. Potential role of novel nucleoside analogs in the treatment of acute myeloid leukemia. Curr Opin Hematol. 2008 Mar;15(2):101-7. doi: 10.1097/MOH.0b013e3282f46e94.

  PMID: 18300755 BACKGROUND

• Faderl S, Ferrajoli A, Wierda W, Huang X, Verstovsek S, Ravandi F, Estrov Z, Borthakur G, Kwari M, Kantarjian HM. Clofarabine combinations as acute myeloid leukemia salvage therapy. Cancer. 2008 Oct 15;113(8):2090-6. doi: 10.1002/cncr.23816.

  PMID: 18756533 BACKGROUND

• Sampat K, Kantarjian H, Borthakur G. Clofarabine: emerging role in leukemias. Expert Opin Investig Drugs. 2009 Oct;18(10):1559-64. doi: 10.1517/13543780903173222.

  PMID: 19715446 BACKGROUND

• Becker PS, Kantarjian HM, Appelbaum FR, Petersdorf SH, Storer B, Pierce S, Shan J, Hendrie PC, Pagel JM, Shustov AR, Stirewalt DL, Faderl S, Harrington E, Estey EH. Clofarabine with high dose cytarabine and granulocyte colony-stimulating factor (G-CSF) priming for relapsed and refractory acute myeloid leukaemia. Br J Haematol. 2011 Oct;155(2):182-9. doi: 10.1111/j.1365-2141.2011.08831.x. Epub 2011 Aug 18.

  PMID: 21848522 BACKGROUND

• Tse E, Leung AY, Sim J, Lee HK, Liu HS, Yip SF, Kwong YL. Clofarabine and high-dose cytosine arabinoside in the treatment of refractory or relapsed acute myeloid leukaemia. Ann Hematol. 2011 Nov;90(11):1277-81. doi: 10.1007/s00277-011-1223-2. Epub 2011 Apr 1.

  PMID: 21455604 BACKGROUND

• Leung AY, Tse E, Hwang YY, Chan TS, Gill H, Chim CS, Lie AK, Kwong YL. Primary treatment of leukemia relapses after allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning second transplantation from the original donor. Am J Hematol. 2013 Jun;88(6):485-91. doi: 10.1002/ajh.23439. Epub 2013 May 2.

  PMID: 23512868 BACKGROUND

• Nazha A, Kantarjian H, Ravandi F, Huang X, Choi S, Garcia-Manero G, Jabbour E, Borthakur G, Kadia T, Konopleva M, Cortes J, Ferrajoli A, Kornblau S, Daver N, Pemmaraju N, Andreeff M, Estrov Z, Du M, Brandt M, Faderl S. Clofarabine, idarubicin, and cytarabine (CIA) as frontline therapy for patients </=60 years with newly diagnosed acute myeloid leukemia. Am J Hematol. 2013 Nov;88(11):961-6. doi: 10.1002/ajh.23544. Epub 2013 Sep 9.

  PMID: 23877926 BACKGROUND

• Vigil CE, Tan W, Deeb G, Sait SN, Block AW, Starostik P, Griffiths EA, Thompson JE, Greene JD, Ford LA, Wang ES, Wetzler M. Phase II trial of clofarabine and daunorubicin as induction therapy for acute myeloid leukemia patients greater than or equal to 60 years of age. Leuk Res. 2013 Nov;37(11):1468-71. doi: 10.1016/j.leukres.2013.07.036. Epub 2013 Aug 15.

  PMID: 24011826 BACKGROUND

• Abbi KK, Rybka W, Ehmann WC, Claxton DF. Phase I/II study of clofarabine, etoposide, and mitoxantrone in patients with refractory or relapsed acute leukemia. Clin Lymphoma Myeloma Leuk. 2015 Jan;15(1):41-6. doi: 10.1016/j.clml.2014.06.005. Epub 2014 Jun 11.

  PMID: 25085441 BACKGROUND

• Gill H, Yim R, Pang HH, Lee P, Chan TSY, Hwang YY, Leung GMK, Ip HW, Leung RYY, Yip SF, Kho B, Lee HKK, Mak V, Chan CC, Lau JSM, Lau CK, Lin SY, Wong RSM, Li W, Ma ESK, Li J, Panagiotou G, Sim JPY, Lie AKW, Kwong YL. Clofarabine, cytarabine, and mitoxantrone in refractory/relapsed acute myeloid leukemia: High response rates and effective bridge to allogeneic hematopoietic stem cell transplantation. Cancer Med. 2020 May;9(10):3371-3382. doi: 10.1002/cam4.2865. Epub 2020 Mar 18.

  PMID: 32187883 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Clofarabine; Mitoxantrone

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds

Study Officials

• Harinder Singh, Harry Gill, MD

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2016
• First Posted: February 19, 2016
• Study Start: February 1, 2016
• Primary Completion: March 31, 2018
• Study Completion: May 1, 2018
• Last Updated: October 6, 2022

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)