Clinical trial NCT00775593: Clofarabine and Temsirolimus in Treating Older Patients With Relapsed or Refractory Acute Myeloid Leukemia
Official title: An Open Label Phase II Trial of Clofarabine and Temsirolimus in Older Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Keywords: 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)
Lead sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto
Sponsor class: OTHER
First posted: 2008-10-20
Enrollment: 60
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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 of intensive 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

Primary outcomes:
measure: Complete Response Rate
timeFrame: At 2 years from study entry
Secondary outcomes:
measure: Number of Serious Adverse Events Within 2 Years
timeFrame: At 2 years from study entry
measure: Duration of Response
timeFrame: At 2 years from study entry
measure: Duration of Survival
timeFrame: At 2 years from study entry
Other outcomes:
Locations:
city: Ancona
country: Italy
facility: Azienda ospedaliera Nuovo ospedale "Torrette"
city: Bari
country: Italy
facility: Azienda Ospedaliero-Universitaria Policlinico Consorziale
city: Bologna
country: Italy
facility: Azienda Ospedaliera Di Bologna Policlinico S. Orsola - Malpighi
city: Catania
country: Italy
facility: Ospedale Ferrarotto
city: Catanzaro
country: Italy
facility: Ospedale Regionale A. Pugliese
city: Napoli
country: Italy
facility: Azienda ospedaliera di Rilievo Nazionale "A. Cardarelli"
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia
city: Novara
country: Italy
facility: S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro
city: Orbassano
country: Italy
facility: A.O. Universitaria S. Luigi Gonzaga di Orbassano
city: Parma
country: Italy
facility: Azienda Ospedaliero - Universitaria di Parma
city: Pescara
country: Italy
facility: Azienda ASL di Pescara
city: Roma
country: Italy
facility: Complesso Ospedaliero S. Giovanni Addolorata
city: Roma
country: Italy
facility: Ospedale S. Eugenio
city: Roma
country: Italy
facility: S.C. di Ematologia e Trapianti - I.F.O. Istituto Nazionale Tumori Regina Elena
city: Roma
country: Italy
facility: Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia
city: Rome
country: Italy
facility: Policlinico di Tor Vergata
city: Rome
country: Italy
facility: Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore
city: Sassari
country: Italy
facility: Serv. di Ematologia Ist. di Ematologia ed Endocrinologia
city: Verona
country: Italy
facility: Policlinico G. B. Rossi - Borgo Roma
Study officials:
affiliation: Ospedale Sant' Eugenio
name: Sergio Amadori, MD
role: PRINCIPAL_INVESTIGATOR
References: