Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Cytarabine

Elacytarabine 2000 mg/m2/d administered as a continuous intravenous infusion (CIV) in a d 1-5 q3w cycle.

Elacytarabine

E.g. cytarabine single agent/combinations, hypomethylating agents, best supportive care (BSC)

Investigator's Choice

David Rizzieri, MD

Francis J Giles, MD, PhD

The purpose of the study is to assess the efficacy and safety of elacytarabine versus investigator's choice treatment in patients with relapsed or refractory acute myeloid leukemia (AML).

The study investigates the new nucleoside analogue derivative, elacytarabine, as treatment for patients with relapsed or refractory Acute Myeloid Leukemia (AML). To be included in the study, patients must have failed to respond to two or three different therapies for AML, or have obtained remission but then relapsed within a relatively short period of time. Patients of age ≥ 65 with adverse cytogenetics can be included in the study after having received one and up to three previous induction/re-induction therapies.

Elacytarabine is an investigational drug which is not commercially available. It is the elaidic acid ester derivative of cytarabine. Cytarabine is routinely used in the treatment of patients with AML. A substantial portion of AML patients have a deficient uptake of cytarabine, often explained by lack of a transport protein (hENT1) in the leukemic cell membrane. Due to the elaidic acid (a naturally occurring fatty acid), cellular uptake of elacytarabine is independent of this transport protein.

Patients included in the study will be randomized to elacytarabine or control treatment. Since there is no standard therapy for relapsed or refractory AML, there is a list of 7 control treatments and the investigator has to choose one that is locked before randomization.

Elacytarabine is given as a continuous infusion over five days, followed by a rest period of minimum two weeks. Investigator's choice treatment is given according to the specific routine.

After each course response evaluation and a decision on further treatment will be made.

Repeated courses of elacytarabine and control treatment might be needed to attain and/or maintain complete remission or clinical benefit.

After the end of study treatment, all patients will be followed for relapse and survival.

Study of Elacytarabine Versus Investigator's Choice in Patients With Late Stage Acute Myeloid Leukaemia (AML)

A Randomised Phase III Study of Elacytarabine vs. Investigator's Choice in Patients With Late Stage Acute Myeloid Leukaemia

Time from date of randomisation until the date of death

* Remission rate measured by overall response rate (ORR) (i.e. complete remission (CR) and complete remission with incomplete bone marrow recovery (CRi))
* Remission rate measured by CR
* Remission duration analysed using cumulative incidence of relapse (CIR) measured from date of CR or CRi

Summaries will include rates of occurrence of any AEs, rates of AEs by system organ classification (SOC),rates of discontinuation of study treatment due to AEs.

Clavis Pharma

Immune System Diseases

Lymphoma

Lymphoma, Mantle-Cell

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Mantle Cell Lymphoma

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Antirheumatic Agents

Gemcitabine

Dexamethasone

Etoposide

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Prednisone

Dexamethasone acetate

Sirolimus

Etoposide phosphate

Chlorambucil

Cladribine

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Temsirolimus 175 mg IV once a week for 3 weeks; followed by 75 mg IV once a week

Temsirolimus (CCI-779)

Temsirolimus 175 mg IV once a week for 3 weeks; followed by 25 mg IV once a week

Any of the following single agent treatments:

1. Fludarabine 25 mg/m2 IV over 30 minutes daily for 5 consecutive days, every 28 days or oral administration, as appropriate.
2. Chlorambucil 0.1 (0.1-0.2) mg/kg PO daily for 3 to 6 weeks as required OR 0.4 (0.3 0.8) mg/kg PO every 21 to 28 days
3. Gemcitabine 1 gm/m2 IV over 30 minutes on days 1, 8 and 15 every 28 days or day 1 and day 8 every 21 days
4. Cyclophosphamide 300 (200-450) mg/m2 PO daily for 5 consecutive days every 21 to 28 days, OR 600 (400-1200) mg/m2 IV every 21 to 28 days
5. Cladribine 5 mg/m2 IV daily for 5 consecutive days, every 28 days for 2-6 cycles depending on response,
6. Etoposide 50 (50-150) mg/m2 IV daily for 3-5 days every 21 to 28 days OR 100 (50 300) mg/m2 PO daily for 3-5 days every 21 to 28 days
7. Prednisone 40 (20-60) mg/m2 PO daily or every other day
8. Dexamethasone 20(20-40) mg PO/IV daily for 5 consecutive days, every 14 - 28 day

Investigator's choice

Pfizer CT.gov Call Center

This is an open-label, randomized trial in relapsed refractory subjects with mantle cell lymphoma (MCL).

Study Evaluating Temsirolimus (CCI-779) In Mantle Cell Lymphoma (MCL)

An Open-Label, Randomized, Phase 3 Trial Of Intravenous Temsirolimus (CCI-779) At Two Dose Levels Compared To Investigator's Choice Therapy In Relapsed, Refractory Subjects With Mantle Cell Lymphoma (MCL)

Overall survival is the duration from randomization to death. For participants who are alive, overall survival is censored at the last contact.

Time between the date of randomization and the first date of objective response for participants with a confirmed objective response.

Time from the first documentation of objective tumor response to first date that recurrence or progressive disease (PD) was objectively documented; censored at last valid tumor assessment.

TTF is defined as the time from randomization to the date of the first documentation of Progressive Disease (PD), the date of treatment discontinuation except completion of treatment, or date of death (any cause).

TTP: time from randomization to first documentation of objective tumor progression (including recurrence); censored at last valid tumor assessment.

The period from randomization until disease progression, death or date of last contact.

Assessment of complete or partial response (CR, PR) or uncomplete response (CRu) using Response Evaluation Criteria in Solid Tumors. CR: 1) No disease evident. 2) Lymph node, nodal mass regressed to normal size. 3) Previously enlarged organ ↓ size. 4) Bone marrow clear on repeat aspirate, biopsy. CRu: CR 1 and 3, at least 1 of following: Lymph node regressed \>75%. Bone marrow ↑ number or aggregate size, no cytologic/architectural atypia. PR: ≥50% ↓ index lesion, no size ↑ in other nodes, liver, spleen. Splenic and hepatic nodule regressed ≥50%. No new disease.

Pfizer

The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.

Temsirolimus 175 milligrams (mg) administered intravenously (IV) once weekly for 3 weeks then 75 mg temsirolimus IV once weekly until disease progression or treatment withdrawal. Includes participants who received Temsirolimus 175/75 mg prior to crossover (Protocol Amendment 5).

Temsirolimus 175/75 mg

Temsirolimus 175 mg IV once weekly for 3 weeks then 25 mg temsirolimus IV once weekly until disease progression or treatment withdrawal.

Temsirolimus 175/25 mg

Participants received 1 single-agent treatment, chosen by investigator:

1. Fludarabine 25 milligram per meter squared (mg/m\^2) IV daily for 5 consecutive days, every 28 days or oral administration, as needed;
2. Chlorambucil 0.1 (0.1-0.2) mg per kilogram, orally (mg/kg, PO) daily for 3 to 6 weeks as required or 0.4 (0.3-0.8) mg/kg PO every 21 to 28 days;
3. Gemcitabine 1 g/m\^2 IV on Days 1, 8, and 15, every 28 days or Days 1 and 8 every 21 days;
4. Cyclophosphamide 300 (200-450) mg/m\^2 PO daily for 5 consecutive days every 21 to 28 days, or 600 (400-1200) mg/m\^2 IV every 21 to 28 days;
5. Cladribine 5 mg/m\^2 IV daily for 5 consecutive days every 28 days for 2-6 cycles;
6. Etoposide 50 (50-150) mg/m\^2 IV daily for 3-5 days every 21 to 28 days or 100 (50-300) mg/m\^2 PO daily for 3-5 days every 21 to 28 days;
7. Prednisone 40 (20-60) mg/m\^2 PO daily or every other day;
8. Dexamethasone 20 (20-40) mg PO/IV daily for 5 consecutive days every 14 to 28 days.

Temsirolimus 175 mg administered IV once weekly for 3 weeks then 25 mg temsirolimus IV once weekly until treatment cross over allowed (via Protocol Amendment 5), then 75 mg temsirolimus IV once weekly until disease progression or treatment withdrawal. Adverse events (AEs) presented for these participants after they crossed over to 75 mg temsirolimus IV once weekly until disease progression or treatment withdrawal.

Temsirolimus 175/25 mg Then 75 mg

Participants received 1 single-agent treatment chosen by investigator until treatment cross over allowed (via Protocol Amendment 5), then temsirolimus 175 mg IV once weekly for 3 weeks; then 75 mg temsirolimus IV once weekly until disease progression or treatment withdrawal. AEs presented for these participants after they crossed over to 75 mg temsirolimus IV once weekly until disease progression or treatment withdrawal.

Investigator's Choice Then Temsirolimus 175/75 mg

Temsirolimus 175 milligrams (mg) administered intravenously (IV) once weekly for 3 weeks then 75 mg temsirolimus IV once weekly until disease progression or treatment withdrawal.

Total

<65 years

>=65 years

Age, Customized

Sex: Female, Male

After the primary analysis was completed, efficacy data was no longer collected nor analyzed; Participants were followed for safety up to 6 months after the last dose of temsirolimus.

Pfizer ClinicalTrials.gov Call Center

Two null hypotheses (Ho) tested: 1. PFS distributions for temsirolimus 175/75 mg and investigator's choice treatment groups are identical. 2. PFS distributions for temsirolimus 175/25 mg and investigator's choice treatment groups are identical. Alternative hypothesis (Ha) for each test was that PFS distributions differed.

Intent-to-Treat (ITT) Population: All randomized participants at time of primary analysis

Progression-Free Survival (PFS)

Percentage of Participants With Objective Response

Overall Survival (OS)

ITT subset of participants with a confirmed objective response

Time to Response

ITT subset of participants who had a response

Duration of Response

Time to Failure (TTF)

Time to Tumor Progression (TTP)

Temsirolimus 175 mg administered IV once weekly for 3 weeks then 25 mg temsirolimus IV once weekly until treatment cross over allowed (via Protocol Amendment 5), then 75 mg temsirolimus IV once weekly until disease progression or treatment withdrawal.

Participants received 1 single-agent treatment chosen by investigator until treatment cross over allowed (via Protocol Amendment 5), then temsirolimus 175 mg IV once weekly for 3 weeks; then 75 mg temsirolimus IV once weekly until disease progression or treatment withdrawal.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Elacytarabine Versus Investigator's Choice in Patients With Late Stage Acute Myeloid Leukaemia (AML)	NCT01147939	Acute Myeloid L...	Elacytarabine Investigator's ...	18 Years -	Clavis Pharma
Study of Elacytarabine Versus Investigator's Choice in Patients With Late Stage Acute Myeloid Leukaemia (AML)	NCT01147939	Acute Myeloid L...	Elacytarabine Investigator's ...	18 Years -	Clavis Pharma
Study of Elacytarabine Versus Investigator's Choice in Patients With Late Stage Acute Myeloid Leukaemia (AML)	NCT01147939	Acute Myeloid L...	Elacytarabine Investigator's ...	18 Years -	Clavis Pharma
Study Evaluating Temsirolimus (CCI-779) In Mantle Cell Lymphoma (MCL)	NCT00117598	Lymphoma	Temsirolimus (C... Temsirolimus (C... Investigator's ...	18 Years -	Pfizer

Spots Global Cancer Trial Database for investigator's choice