Pilot Study Of Sirolimus Plus Multiagent Chemotherapy For Relapsed/Refractory Acute Lymphoblastic Leukemia/Lymphoma

NCT01658007 | Terminated Early Phase 1 DMC FDA Drug

• 2 other identifiers: SIR-MO-11012012-0361
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators want to learn about treating relapsed/refractory lymphoblastic leukemia and lymphoma with a drug called sirolimus. The investigators are using sirolimus along with other cancer drugs that are often given to patients with relapsed leukemia and lymphoma. The main purpose of this study is to determine if sirolimus can be given safely in combination with standard drugs used to treat relapsed lymphoblastic leukemia/lymphoma.

Conditions

Relapsed Lymphoblastic Leukemia; Recurrent Adult Lymphoblastic Lymphoma; Refractory Acute Lymphoblastic Leukemia; Refractory Lymphoblastic Lymphoma

Outcome Measures

Primary Outcomes (2)

• Determine rate of dose limiting toxicities

  The safety of the regimen will be assessed by the occurrence of unexpected or severe adverse events attributable to sirolimus

  35 days

• Number of participants with adverse events to determine maximum tolerated level of sirolimus in combination with chemotherapy

  MAST (maximum acceptable sirolimus trough) will be the serum trough range at which fewer than one third of patients experience dose limiting toxicities during the observation period (28 days)

  28 Days

Secondary Outcomes (4)

• Measure the number of residual leukemia cells in the bone marrow.

  At day 35 of induction and day 56 of consolidation

• Measure protein phosphorylation

  Samples collected at Baseline, Days 1, 3, 8 and 29 of induction and Baseline, and Days 1, 8, 29, and 36.

• Tumor measurement by PET and/or CT scan

  After day 35 of induction and/or Day 56 of Consolidation

• Measure changes in sirolimus plasma concentration (ng/ml).

  56 Days

Study Arms (1)

Sirolimus

EXPERIMENTAL

Adding sirolimus to established induction and consolidation chemotherapy for relapsed/refractory acute lymphoblastic leuk

Drug: Sirolimus

Interventions

Sirolimus DRUG

Adding sirolimus to established induction and consolidation chemotherapy for relapsed/refractory acute lymphoblastic leukemia

Also known as: Rapamycin, Rapamune

Sirolimus

Eligibility Criteria

• Age: Up to 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age: Patients must be \< 30 years of age at the time of enrollment
• Diagnosis
• Acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL)
• Histology: B-precursor or T-cell
• Disease status: first or greater relapse OR primary disease refractory to two prior induction attempts
• Patients with active relapse (\> 5% bone marrow blasts if ALL, detectable disease by imaging with CT and/or PET scan if LL) without prior re-induction attempt are eligible for induction (block 1) therapy followed by consolidation (block 2) therapy
• Patients with documented history of relapse who have received alternative induction therapy are eligible for consolidation (block 2) therapy
• Patients with CNS involvement are eligible for the induction block with intensified intrathecal therapy. Those enrolling post-induction for the consolidation block must have cleared the CNS of blasts at the time of enrollment on this study. (See Appendix I for method of evaluating traumatic lumbar punctures.)
• Performance status
• Karnofsky \>/= 50 for patients \> 10 years of age OR Lansky \>/= 50 for children \</= 10 years of age (see Appendix II).
• Oral medication -Patient must be able to consume oral medication in the form of solution or have nasogastric tube placed for administration of medication.
• Prior Therapy
• Patients who relapse while receiving standard ALL maintenance chemotherapy will not be required to have a waiting period before entry onto this study.
• Patients who relapse on therapy other than standard ALL maintenance therapy must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study, unless deemed stable and irreversible by the investigator.

You may not qualify if:

• Cytotoxic chemotherapy: At least 7 days must have elapsed from prior cytotoxic chemotherapy regimen before initiation of treatment with sirolimus on this trial, including administration of treatment dosing of corticosteroids (physiologic replacement for adrenal insufficiency is allowed)
• Hydroxyurea: patients with peripheral blasts may receive hydroxyurea until the first dose of cytotoxic chemotherapy for cytoreduction.
• Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor.
• Biologic (anti-neoplastic) agent: At least 7 days after the last dose of a biologic agent or donor lymphocyte infusion (DLI). For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair.
• Immunotherapy: At least 6 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines.
• Monoclonal antibodies: At least 3 half-lives since prior therapy with a monoclonal antibody.
• XRT: \>/= 2 wks for local palliative XRT (small port); \>/= 24 weeks must have elapsed if prior TBI, craniospinal XRT or if \>/= 50% radiation of pelvis; \>/= 6 weeks must have elapsed if other substantial bone marrow radiation.
• Stem Cell Transplant or Rescue without TBI: No evidence of active graft vs. host disease and ≥ 12 weeks must have elapsed since transplant or stem cell infusion.
• Organ Function Requirements
• Adequate Renal Function Defined as:
• Creatinine clearance or radioisotope GFR \>/= 70ml/min/1.73 m2 or
• A serum creatinine based on age/gender as follows:
• The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the CDC.
• Adequate Liver Function Defined as:
• Total bilirubin \>/= 1.5 x upper limit of normal (ULN) for age

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Maureen O'Brien, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2012
• First Posted: August 6, 2012
• Study Start: August 1, 2012
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2017
• Last Updated: September 14, 2020

Record last verified: 2017-09

Locations

US (1)