Depocyte in the Treatment of CNS Relapse in Patients With Lymphoblastic Leucemia or Very Aggressive Lymphoma - Full Text View

Purpose

The first purpose is to confirm or not the efficacy of only one administration of DepoCyte®.

Condition	Intervention	Phase
Lymphoblastic Leukemia Lymphoma	Drug: Depocyte®	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Multicenter, Prospective, Open Label Trial, Uncontrolled to Determine the Efficacy and Safety of Depocyt ® for the Treatment of CNS Relapse in Adult Patients With Lymphoblastic Leucemia or Very Aggressive Lymphoma

Resource links provided by NLM:

MedlinePlus related topics: Chronic Lymphocytic Leukemia Leukemia Lymphoma

U.S. FDA Resources

Further study details as provided by PETHEMA Foundation:

Primary Outcome Measures:

The primary purpose: [ Time Frame: 1 year ] [ Designated as safety issue: No ]
response rate after one application of DepoCyte®. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Death in induction and in CR, Time to neurological progression, The frequency of improvement in pre-existing meningeal-disease related neurological symptoms,Karnofsky Performance Status,Survival,Toxicity according to CTCAE v.3 [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	10
Study Start Date:	March 2006
Study Completion Date:	June 2011
Primary Completion Date:	March 2011 (Final data collection date for primary outcome measure)

Intervention Details:

Depocyte® is a cytostatic drug

Detailed Description:

It is a clinical study multicenter, prospective, open label trial, uncontrolled and nonrandomized

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with acute lymphoblastic leukemia or very aggressive Non-Hodgkin-Lymphoma (Burkitt/Burkitt-like) and CNS relapse.

CNS involvement must be demonstrated by:

A positive ventricular or lumbar CSF cytology defined as CSF cell counts > 5/µl (19/3 cells), obtained within 10 days prior to inclusion OR
Characteristic signs and symptoms of neoplastic meningitis PLUS an MRI or CT scan indicating the presence of meningeal involvement. Patients with combined relapse in CNS and other locations may be included in case that systemic therapy with CNS active drugs (HDMTX;HDAC, Thiotepa) can be postponed for at least 2 weeks.
- Karnofsky >60%
- Age >18 years old
- Recovery from grade III/IV toxicities attributable to prior treatment with the exception of hematotoxicity.
- No severe heart, lung, liver or kidney dysfunction.
- The patient or guardian must be competent to provide informed consent and must provide written informed consent prior to the initiation of study procedures

Exclusion Criteria:

Failure (as defined by no clearance of the CSF) to > 1 dose of prior intrathecal MTX or cytarabine or triple (MTX, ARAC, dexamethasone) therapy
History of previous severe neurotoxicity (grade III-IV) attributed to intrathecal therapy or systemic high-dose therapy with methotrexate or cytarabine (vincristine induced peripheral neuropathy is accepted)
Prior CNS relapse < 1 month before
uncontrolled infection
The patient must not be pregnant or breast feeding. If the patient is a female of child-bearing potential she must have a negative (urine or serum) pregnancy test and be using effective methods to prevent pregnancy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00388531

Locations

Spain
Hospital "Santa Creu i Sant Pau"
Barcelona, Spain
Hospital Germans Trias i Pujol
Barcelona, Spain
Hospital Clínico y Provincial de Barcelona
Barcelona, Spain
Hospital Clínico San Carlos de Madrid
Madrid, Spain
Hospital Doce de Octubre
Madrid, Spain
. Hospital Clínico Universitario Virgen de la Victoria
Málaga, Spain
Hospital Clínico Universitario de Salamanca
Salamanca, Spain
Hospital Universitario Virgen del Rocío
Sevilla, Spain
Hospital La Fe
Valencia, Spain

Sponsors and Collaborators

PETHEMA Foundation

Investigators

Study Chair:

Josep Mª Ribera, Doctor

HOSPITAL GERMANS TRIAS I PUJOL

More Information

Additional Information:

Spanish association of Haematology This link exits the ClinicalTrials.gov site

CRO

Publications:

Mastrangelo R, Poplack D, Bleyer A, Riccardi R, Sather H, D'Angio G. Report and recommendations of the Rome workshop concerning poor-prognosis acute lymphoblastic leukemia in children: biologic bases for staging, stratification, and treatment. Med Pediatr Oncol. 1986;14(3):191-4. No abstract available.

Gokbuget N, Hoelzer D. Meningeosis leukaemica in adult acute lymphoblastic leukaemia. J Neurooncol. 1998 Jun-Jul;38(2-3):167-80. Review.

Neale GA, Pui CH, Mahmoud HH, Mirro J Jr, Crist WM, Rivera GK, Goorha RM. Molecular evidence for minimal residual bone marrow disease in children with 'isolated' extra-medullary relapse of T-cell acute lymphoblastic leukemia. Leukemia. 1994 May;8(5):768-75.

Ribeiro RC, Rivera GK, Hudson M, Mulhern RK, Hancock ML, Kun L, Mahmoud H, Sandlund JT, Crist WM, Pui CH. An intensive re-treatment protocol for children with an isolated CNS relapse of acute lymphoblastic leukemia. J Clin Oncol. 1995 Feb;13(2):333-8.

Larson RA, Dodge RK, Burns CP, Lee EJ, Stone RM, Schulman P, Duggan D, Davey FR, Sobol RE, Frankel SR, et al. A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811. Blood. 1995 Apr 15;85(8):2025-37.

Mandelli F, Annino L, Rotoli B. The GIMEMA ALL 0183 trial: analysis of 10-year follow-up. GIMEMA Cooperative Group, Italy. Br J Haematol. 1996 Mar;92(3):665-72.

Morra E, Lazzarino M, Brusamolino E, Pagnucco G, Castagnola C, Bernasconi P, Orlandi E, Corso A, Santagostino A, Bernasconi C. The role of systemic high-dose cytarabine in the treatment of central nervous system leukemia. Clinical results in 46 patients. Cancer. 1993 Jul 15;72(2):439-45.

Ellison RR, Mick R, Cuttner J, Schiffer CA, Silver RT, Henderson ES, Woliver T, Royston I, Davey FR, Glicksman AS, et al. The effects of postinduction intensification treatment with cytarabine and daunorubicin in adult acute lymphocytic leukemia: a prospective randomized clinical trial by Cancer and Leukemia Group B. J Clin Oncol. 1991 Nov;9(11):2002-15.

Durrant IJ, Richards SM. Results of Medical Research Council trial UKALL IX in acute lymphoblastic leukaemia in adults: report from the Medical Research Council Working Party on Adult Leukaemia. Br J Haematol. 1993 Sep;85(1):84-92.

Elonen E, Almqvist A, Hänninen A et al. Intensive treatment of acute lymphatic leukaemia in adults: ALL86 protocol. Haematologica. 1991;76 (Suppl 4):133

Gökbuget N, Aguion-Freire E, Diedrich H et al. Characteristics and outcome of CNS relapse in patients with acute lymphoblastic leukemia (ALL) [abstract]. Blood. 1999;94:1287a.

Gökbuget N, Arnold R, Eggeling B et al. Prospective evaluation of neurotoxicity of prophylactic intrathecal therapy in adult acute lymphoblastic leukemia. The Hematology Journal. 2000;1:591a.

Chessells JM. Central nervous system directed therapy in acute lymphoblastic leukaemia. Baillieres Clin Haematol. 1994 Jun;7(2):349-63. Review.

Gagliano RG, Costanzi JJ. Paraplegia following intrathecal methotrexate: report of a case and review of the literature. Cancer. 1976 Apr;37(4):1663-8.

Dunton SF, Nitschke R, Spruce WE, Bodensteiner J, Krous HF. Progressive ascending paralysis following administration of intrathecal and intravenous cytosine arabinoside. A Pediatric Oncology Group study. Cancer. 1986 Mar 15;57(6):1083-8.

Bleyer WA, Poplack DG. Prophylaxis and treatment of leukemia in the central nervous system and other sanctuaries. Semin Oncol. 1985 Jun;12(2):131-48. Review. No abstract available.

Glass JP, Lee YY, Bruner J, Fields WS. Treatment-related leukoencephalopathy. A study of three cases and literature review. Medicine (Baltimore). 1986 May;65(3):154-62. Review.

Graham FL, Whitmore GF. The effect of-beta-D-arabinofuranosylcytosine on growth, viability, and DNA synthesis of mouse L-cells. Cancer Res. 1970 Nov;30(11):2627-35. No abstract available.

Zimm S, Collins JM, Curt GA, O'Neill D, Poplack DG. Cerebrospinal fluid pharmacokinetics of intraventricular and intravenous aziridinylbenzoquinone. Cancer Res. 1984 Apr;44(4):1698-701.

Murry DJ, Blaney SM. Clinical pharmacology of encapsulated sustained-release cytarabine. Ann Pharmacother. 2000 Oct;34(10):1173-8. Review.

Kim S, Chatelut E, Kim JC, Howell SB, Cates C, Kormanik PA, Chamberlain MC. Extended CSF cytarabine exposure following intrathecal administration of DTC 101. J Clin Oncol. 1993 Nov;11(11):2186-93.

Chamberlain MC, Khatibi S, Kim JC, Howell SB, Chatelut E, Kim S. Treatment of leptomeningeal metastasis with intraventricular administration of depot cytarabine (DTC 101). A phase I study. Arch Neurol. 1993 Mar;50(3):261-4.

Chamberlain MC, Kormanik P, Howell SB, Kim S. Pharmacokinetics of intralumbar DTC-101 for the treatment of leptomeningeal metastases. Arch Neurol. 1995 Sep;52(9):912-7.

Glantz MJ, LaFollette S, Jaeckle KA, Shapiro W, Swinnen L, Rozental JR, Phuphanich S, Rogers LR, Gutheil JC, Batchelor T, Lyter D, Chamberlain M, Maria BL, Schiffer C, Bashir R, Thomas D, Cowens W, Howell SB. Randomized trial of a slow-release versus a standard formulation of cytarabine for the intrathecal treatment of lymphomatous meningitis. J Clin Oncol. 1999 Oct;17(10):3110-6.

Howell SB. Liposomal cytarabine for the treatment of lymphomatous meningitis. Biological Therapy of Lymphoma. 2003;6:10-14.

Glantz MJ, Jaeckle KA, Chamberlain MC, Phuphanich S, Recht L, Swinnen LJ, Maria B, LaFollette S, Schumann GB, Cole BF, Howell SB. A randomized controlled trial comparing intrathecal sustained-release cytarabine (DepoCyt) to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors. Clin Cancer Res. 1999 Nov;5(11):3394-402.

Bomgaars J, Geyer J, Franklin J, et al. A phase I study of intrathecal liposomal cytarabine (DepoCyt) in pediatric patients with advanced meningeal malignancies. Proc Am Soc Clin Oncol. 2002;Abstract 433.

Jaeckle KA, Phuphanich S, Bent MJ, Aiken R, Batchelor T, Campbell T, Fulton D, Gilbert M, Heros D, Rogers L, O'Day SJ, Akerley W, Allen J, Baidas S, Gertler SZ, Greenberg HS, LaFollette S, Lesser G, Mason W, Recht L, Wong E, Chamberlain MC, Cohn A, Glantz MJ, Gutheil JC, Maria B, Moots P, New P, Russell C, Shapiro W, Swinnen L, Howell SB. Intrathecal treatment of neoplastic meningitis due to breast cancer with a slow-release formulation of cytarabine. Br J Cancer. 2001 Jan;84(2):157-63.

Jaeckle KA, Batchelor T, O'Day SJ, Phuphanich S, New P, Lesser G, Cohn A, Gilbert M, Aiken R, Heros D, Rogers L, Wong E, Fulton D, Gutheil JC, Baidas S, Kennedy JM, Mason W, Moots P, Russell C, Swinnen LJ, Howell SB. An open label trial of sustained-release cytarabine (DepoCyt) for the intrathecal treatment of solid tumor neoplastic meningitis. J Neurooncol. 2002 May;57(3):231-9.

Responsible Party:	Pethema, pethema
ClinicalTrials.gov Identifier:	NCT00388531 History of Changes
Other Study ID Numbers:	2004-004414-17, DEPOCYLAN
Study First Received:	October 16, 2006
Last Updated:	September 16, 2011
Health Authority:	Spain: Ministry of Health and Consumption

Keywords provided by PETHEMA Foundation:

Acute Lymphoblastic Leucemia
Aggressive Non-Hodgkin-Lymphoma
CNS relapse
Cytarabine liposome

Additional relevant MeSH terms:

Aggression
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma
Behavioral Symptoms

Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on June 18, 2013