Study of Sirolimus With PEG-Asparaginase in Acute Lymphoblastic Leukemia (ALL)

NCT00957320 | Withdrawn Phase 1 DMC

• 2 other identifiers: IRB00015324Sirolimus
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to find a safe dose of sirolimus that can be used with a standard dose of L-asparaginase. To find the safe dose, the investigators will give the first patient a very small dose of sirolimus (smaller than the dose used in organ transplant children) and the standard dose of L-asparaginase. The investigators will then look for side effects. If side effects develop, the investigators will decrease the dose of sirolimus. If they do not, the investigators will increase the dose of sirolimus in the next patient on the study. The investigators will continue this method until fewer than one-third of patients have a side effect that would require stopping the drug or changing the dose. The investigators plan to enroll up to 15 children with relapsed ALL. The enrolled patients must have recovered from other treatment before starting this study. Also, they cannot have severe side effects from their earlier therapy that will possibly make these drugs less safe. The investigators will collect information on whether these drugs help to cure the ALL, but the purpose will be to find a dose of sirolimus that does not cause too many side effects when combined with L-asparaginase. This will be explained to the families and they will sign a written consent. The patients will provide either verbal or written assent when appropriate.

Conditions

Acute Lymphoblastic Leukemia

Keywords

leukemia; cancer; oncology; sirolimus; ALL

Outcome Measures

Primary Outcomes (2)

• To estimate the maximum tolerated dose (MTD) of sirolimus in children with refractory or recurrent acute lymphoblastic leukemia (ALL) who are concurrently receiving PEG-asparaginase.

  end of study

• To determine the dose limiting toxicities of sirolimus in combination with PEG-asparaginase in this Phase I Study.

  end of study

Secondary Outcomes (2)

• To use phospho-flow to measure the degree of phosphorylation of signaling pathway proteins in response to specific stimulating events in bone marrow derived leukemia cells obtained at the time of study entry and at day 15 and 29.

  end of study

• To correlate the signal pathway phosphorylation to clinical response to the chemotherapy regimen used in this study.

  end of study

Study Arms (1)

1

EXPERIMENTAL

Subjects will receive PEG-asparaginase at a fixed weekly dose, as per published reports in relapsed childhood ALL. The dose of sirolimus will be dose escalated following standard phase 1 statistical methods. For patients with active CNS leukemia, intrathecal methotrexate, hydrocortisone and cytarabine (triple IT) will be administered weekly, with leucovorin rescue at the treating physician's discretion.

Drug: Sirolimus; Drug: PEG-asparaginase

Interventions

Sirolimus DRUG

Sirolimus daily po days 1 through 28, Dose level 0: 0.25 mg/m2 po daily Dose level 1: 0.5 mg/m2 po daily Dose level 2: 1 mg/m2 po daily Dose level 3 1.5 mg/m2 po daily Dose level 4 2 mg/m2 po daily

1

PEG-asparaginase DRUG

Subjects will receive PEG-asparaginase at a fixed weekly dose, as per published reports in relapsed childhood ALL.

1

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Less than 21 years old.
• Acute lymphoblastic leukemia.
• Second or greater bone marrow relapse or 1st relapse and refractory to at least 2 Attempts at re-induction.
• Life expectancy of at least 8 weeks.
• Fully recovered from the acute toxic effects of all prior therapy.
• Appropriate organ function.

You may not qualify if:

• Patients with a documented history of ≥ grade 3 local or systemic reactions to PEG-asparaginase.
• Patients with a documented history of anti-E. coli asparaginase antibodies.
• Patients with a history of ≥ grade 3 pancreatitis.
• Patients with an active and uncontrolled infection.
• Patients s/p allogeneic bone marrow transplantation, who are still on immunosuppressants.
• Pregnant or lactating females. Women of childbearing age will agree to use contraception during the protocol.
• Patients currently receiving other investigational agents, medications, or supplements with a known anti-leukemic effect.
• Other concomitant medications that may alter the metabolism of Sirolimus (See section 7.2).
• Patients who, in the opinion of the investigator, will not be able to comply with safety monitoring requirements of the study.
• Patients with a history of a documented thrombus from previous asparaginase therapy.

Sponsors & Collaborators

• Emory University: lead

Study Sites (1)

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia; Neoplasms

Interventions

Sirolimus; pegaspargase

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Frank Keller, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 11, 2009
• First Posted: August 12, 2009
• Study Start: June 1, 2009
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: December 3, 2013

Record last verified: 2012-11

Locations

US (1)