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

NCT ID: NCT00775593

Last Updated: 2017-11-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2013-10-23

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.

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)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

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

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gruppo Italiano Malattie EMatologiche dell'Adulto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sergio Amadori, MD

Role: PRINCIPAL_INVESTIGATOR

Ospedale Sant' Eugenio

Locations

Azienda ospedaliera Nuovo ospedale "Torrette"

Ancona, , Italy

Azienda Ospedaliero-Universitaria Policlinico Consorziale

Bari, , Italy

Azienda Ospedaliera Di Bologna Policlinico S. Orsola - Malpighi

Bologna, , Italy

Ospedale Ferrarotto

Catania, , Italy

Ospedale Regionale A. Pugliese

Catanzaro, , Italy

Azienda ospedaliera di Rilievo Nazionale "A. Cardarelli"

Napoli, , Italy

Azienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia

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

Complesso Ospedaliero S. Giovanni Addolorata

Roma, , Italy

Ospedale S. Eugenio

Roma, , Italy

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

Policlinico di Tor Vergata

Rome, , Italy

Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore

Rome, , Italy

Serv. di Ematologia Ist. di Ematologia ed Endocrinologia

Sassari, , Italy

Policlinico G. B. Rossi - Borgo Roma

Verona, , Italy

Countries

Italy

Other Identifiers

GIMEMA-AML-1107

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2007-005374-31

Identifier Type: -

Identifier Source: secondary_id

AML1107

Identifier Type: -

Identifier Source: org_study_id