Clofarabine and Temsirolimus in Treating Older Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML1107)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier:
NCT00775593
First received: October 17, 2008
Last updated: November 4, 2013
Last verified: November 2013
  Purpose

RATIONALE: Drugs used in chemotherapy, such as clofarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Temsirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving clofarabine together with temsirolimus may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving clofarabine together with temsirolimus works in treating older patients with relapsed or refractory acute myeloid leukemia.


Condition Intervention Phase
Leukemia
Drug: clofarabine
Drug: temsirolimus
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Phase II Trial of Clofarabine and Temsirolimus in Older Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)

Resource links provided by NLM:


Further study details as provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:

Primary Outcome Measures:
  • Complete response rate [ Time Frame: At 2 years from study entry ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Tolerability and safety [ Time Frame: At 2 years from study entry ] [ Designated as safety issue: Yes ]
  • Duration of response [ Time Frame: At 2 years from study entry ] [ Designated as safety issue: No ]
  • Duration of survival [ Time Frame: At 2 years from study entry ] [ Designated as safety issue: No ]

Enrollment: 60
Study Start Date: December 2008
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: clofarabine

    Patients will receive one course of low-dose Clofarabine in combination with Temsirolimus (CloTor regimen) for remission induction.

    Induction therapy

    - Clofarabine 20 mg/m2/day, administered by iv infusion over 1 hour on days 1 through 5

    Drug: temsirolimus

    Those who achieve morphologic CR and morphologic CRi will receive maintenance treatment with Temsirolimus monthly for 12 months, or until relapse.

    Those who achieve a PR will receive one additional course of CloTor and, if a CR/CRi is obtained, maintenance treatment with Temsirolimus as above.

    Induction therapy:

    - Temsirolimus 25 mg (flat dose) administered iv over 30 minutes on days 1, 8 and 15.

    Maintenance therapy:

    - Temsirolimus 25 mg (flat dose) administered iv over 30 minutes on days 1 and 8 of each month for 12 months, or until relapse.

Detailed Description:

OBJECTIVES:

Primary

  • To determine the complete response rate in older patients with relapsed or refractory acute myeloid leukemia when treated with low-dose clofarabine and temsirolimus.

Secondary

  • To determine the tolerability and safety of this regimen.
  • To determine the duration of response.
  • To determine the duration of survival.

OUTLINE: This is a multicenter study.

  • Induction therapy: Patients receive clofarabine IV over 1 hour on days 1-5 and temsirolimus IV over 30 minutes on days 1, 8, and 15. Treatment continues for 1-2 courses in the absence of disease progression or unacceptable toxicity.
  • Maintenance therapy: Patients achieving morphologic complete remission (CR) or CR with incomplete blood count recovery receive temsirolimus IV over 30 minutes on days 1 and 8 of each month. Treatment continues for 12 months in the absence of disease progression or unacceptable toxicity.
  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Cytologically confirmed acute myeloid leukemia (AML) meeting the following criteria:

    • At least 20% of blasts in the bone marrow
    • AML in first relapse OR refractory to no more than one prior combination chemotherapy induction regimen
  • No acute promyelocytic leukemia
  • No blast transformation of chronic myeloid leukemia or other myeloproliferative disorders
  • No active CNS leukemia

PATIENT CHARACTERISTICS:

  • WHO performance status 0-2
  • Life expectancy ≥ 4 weeks
  • Serum total bilirubin ≤ 1.5 times upper limit of normal (ULN)*
  • AST and ALT ≤ 2.5 times ULN*
  • Serum creatinine ≤ 1.0 mg/dL* OR estimated glomerular filtration rate > 60 mL/min
  • No active uncontrolled systemic infection
  • No concurrent active malignancy
  • No HIV positivity
  • No severe concurrent medical condition or psychiatric disorder that would preclude study participation NOTE: *Unless due to organ leukemic involvement

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • More than 2 weeks since prior myelosuppressive chemotherapy
  • At least 48 hours since prior hydroxyurea
  • No prior clofarabine or temsirolimus
  • No prior allogeneic stem cell transplantation
  • No investigational drug within the past 30 days
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00775593

Locations
Italy
Azienda ospedaliera Nuovo ospedale "Torrette"
Ancona, Italy
Azienda Ospedaliero-Universitaria Policlinico Consorziale
Bari, Italy
Azienda Ospedaliera Di Bologna Policlinico S. Orsola - Malpighi
Bologna, Italy, 40138
Ospedale Ferrarotto
Catania, Italy, 95124
Ospedale Regionale A. Pugliese
Catanzaro, Italy, 88100
Azienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia
Napoli, Italy
Azienda ospedaliera di Rilievo Nazionale "A. Cardarelli"
Napoli, Italy
S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro
Novara, Italy
A.O. Universitaria S. Luigi Gonzaga di Orbassano
Orbassano, Italy
Azienda Ospedaliero - Universitaria di Parma
Parma, Italy
Azienda ASL di Pescara
Pescara, Italy, 61100
S.C. di Ematologia e Trapianti - I.F.O. Istituto Nazionale Tumori Regina Elena
Roma, Italy
Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia
Roma, Italy
Ospedale S. Eugenio
Roma, Italy
Complesso Ospedaliero S. Giovanni Addolorata
Roma, Italy
Policlinico di Tor Vergata
Rome, Italy, 00133
Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore
Rome, Italy, 00168
Serv. di Ematologia Ist. di Ematologia ed Endocrinologia
Sassari, Italy
Policlinico G. B. Rossi - Borgo Roma
Verona, Italy, 37134
Sponsors and Collaborators
Gruppo Italiano Malattie EMatologiche dell'Adulto
Investigators
Principal Investigator: Sergio Amadori, MD Ospedale Sant' Eugenio
  More Information

Additional Information:
No publications provided

Responsible Party: Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier: NCT00775593     History of Changes
Other Study ID Numbers: AML1107, GIMEMA-AML-1107, EUDRACT-2007-005374-31, EU-20886, WYETH-GIMEMA-AML-1107
Study First Received: October 17, 2008
Last Updated: November 4, 2013
Health Authority: Italy: Ethics Committee

Keywords provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:
recurrent adult acute myeloid leukemia
adult acute basophilic leukemia
adult acute eosinophilic leukemia
adult erythroleukemia (M6a)
adult pure erythroid leukemia (M6b)
adult acute megakaryoblastic leukemia (M7)
adult acute minimally differentiated myeloid leukemia (M0)
adult acute monoblastic leukemia (M5a)
adult acute monocytic leukemia (M5b)
adult acute myeloblastic leukemia with maturation (M2)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myelomonocytic leukemia (M4)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute myeloid leukemia with inv(16)(p13;q22)

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia
Neoplasms by Histologic Type
Neoplasms
Sirolimus
Everolimus
Clofarabine
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 01, 2014