Alemtuzumab and Combination Chemotherapy in Treating Patients With Untreated Acute Lymphoblastic Leukemia - Full Text View

Sponsor:	Cancer and Leukemia Group B
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Cancer and Leukemia Group B
ClinicalTrials.gov Identifier:	NCT00061945

Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as alemtuzumab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining chemotherapy with monoclonal antibody therapy may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of alemtuzumab and to see how well it works when given together with combination chemotherapy in patients with previously untreated acute lymphoblastic leukemia.

Condition	Intervention	Phase
Leukemia	Biological: alemtuzumab Biological: filgrastim Drug: asparaginase Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride Drug: dexamethasone Drug: imatinib mesylate Drug: leucovorin calcium Drug: mercaptopurine Drug: methotrexate Drug: vincristine sulfate Drug: Allopurinol	Phase I Phase II

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:	A Phase I/II Dose Escalation Study of Subcutaneous Campath-1H (NSC #715969, IND #10864) During Intensification Therapy in Adults With Untreated Acute Lymphoblastic Leukemia (ALL)

Resource links provided by NLM:

MedlinePlus related topics: Acute Lymphocytic Leukemia Cancer Chronic Lymphocytic Leukemia Leukemia

Drug Information available for: Dexamethasone Cyclophosphamide 6-Mercaptopurine Vincristine Leucovorin Methotrexate Cytarabine hydrochloride Allopurinol sodium Daunorubicin Daunorubicin hydrochloride Citrovorum factor Dexamethasone acetate Doxiproct plus Filgrastim Campath Lenograstim Granulocyte colony-stimulating factor Imatinib Alemtuzumab Imatinib mesylate Cytarabine Allopurinol Leucovorin Calcium Dexamethasone Sodium Phosphate Vincristine sulfate Folinic acid calcium salt pentahydrate Mercaptopurine L-Asparaginase

U.S. FDA Resources

Further study details as provided by Cancer and Leukemia Group B:

Primary Outcome Measures:

Toxicity: dose escalation (Phase 1) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
determination of the feasibility and toxicity profiles of escalating doses of Campath-1H
Feasibility (Phase 2) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Disease-free survival (DFS) (Phase II) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Overall survival (OS) (Phase II) [ Time Frame: up to 10 yrs from study entry ] [ Designated as safety issue: No ]

Enrollment:	302
Study Start Date:	June 2003
Estimated Study Completion Date:	May 2017
Primary Completion Date:	November 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Alemtuzumab and combination chemotherapy Alemtuzumab dosing is characterized in conjunction with chemotherapy for adults with untreated acute ALL	Biological: alemtuzumab 3 cohorts receive 10, 20, or 30 mg alemtuzumab sub Q injection 3 times/wk for 4 wks in Module D of Phases I and II Other Name: Campath-1H Biological: filgrastim Mod A, courses I & V: 5 ug/kg/day subQ inj start on D4 for at 7 days, then until abs neutrophil count is > 5000/uL Mod B, courses II & IV: 5 ug/kg/day subQ inj start on D 4, con't until abs neutrophil count is > 5000/uL Other Name: G-CSF Drug: asparaginase 6000U/sq m subQ on days 5,8,15,18, 22 of Mod A, Courses I & V and days 15, 18, 22 of Mod B Courses II & VI Drug: cyclophosphamide For pts < = 60 y/o 1200 mg/sq m IV infusion over 15-30 min on day 1 Mod A courses I & V For all pts 1000 mg/sq m IV infusion over 15-30 min day 1 of Mod B courses II & VI Drug: cytarabine 2000 mg/sq m IV infusion over 3 hrs days 1, 2, 3 Mod B, courses II & VI Other Name: ara-C Drug: daunorubicin hydrochloride 80 mg/sq m/day slow IV infusion days 1, 2, 3 Mod A Courses I & V 60 mg/sq m/day slow IV infusion days 1, 2, 3 Mod B Courses II & VI Drug: dexamethasone 5 mg/sq m PO bid days 1-7 and for pts < = 60y/o days 15-21 Mod A, Course I and days 1-7 for Course V 0.1% eye drops 2 drops qid & prn ea eye days 1-4 Mod B courses II & VI 6 mg/sq m PO days 1-5 of ea maintenance cycle (Course VIII) Drug: imatinib mesylate For PH+ patients only: 400 mg PO/day d 15 or later- d 28 Mod A, Courses I & V; d 1-28 Mod B, courses II & VI, and d 1-42 Mod C courses III & VII 600 mg/day PO d 1 of month 1 maintenance until protocol tx is completed Drug: leucovorin calcium 25 mg/sq m IV push 6 hrs post last MTX Mod C courses III & VII on days 2,16,30 10 mg PO q 6 hrs for 8 doses or until serum MTX < 0.05 uM starting 12 hrs after last IV dose Drug: mercaptopurine 60 mg/sq m per day days 1-35 Mod C courses III & VII and during maintenance Drug: methotrexate Intrathecal 15 mg d 1 Mod B Courses II & VI & d 1,15,29 Mod C courses III & VII IV 1000 mg/sq m d 1,15,29 Mod C courses III & VII PO 25 mg/sq m q 6 hrs 4 doses (starting 6 h post IV MTX) on days 1,2,15,16,29,30 Mod C courses III & VII; PO 20mg/sq m d 1,8,15,22 of ea maintenance cycle Drug: vincristine sulfate 2 mg IV push d 1,8,15,22 Mod A courses I & V d 1, 15, 29 Mod C courses III & VII d 1 ea maintenance cycle Drug: Allopurinol 300 mg PO days 1-14 Mod A Course I

Arms

Assigned Interventions

Experimental: Alemtuzumab and combination chemotherapy

Alemtuzumab dosing is characterized in conjunction with chemotherapy for adults with untreated acute ALL

Biological: alemtuzumab

3 cohorts receive 10, 20, or 30 mg alemtuzumab sub Q injection 3 times/wk for 4 wks in Module D of Phases I and II

Other Name: Campath-1H

Biological: filgrastim

Mod A, courses I & V: 5 ug/kg/day subQ inj start on D4 for at 7 days, then until abs neutrophil count is > 5000/uL Mod B, courses II & IV: 5 ug/kg/day subQ inj start on D 4, con't until abs neutrophil count is > 5000/uL

Other Name: G-CSF

Drug: asparaginase

6000U/sq m subQ on days 5,8,15,18, 22 of Mod A, Courses I & V and days 15, 18, 22 of Mod B Courses II & VI

Drug: cyclophosphamide

For pts < = 60 y/o 1200 mg/sq m IV infusion over 15-30 min on day 1 Mod A courses I & V For all pts 1000 mg/sq m IV infusion over 15-30 min day 1 of Mod B courses II & VI

Drug: cytarabine

2000 mg/sq m IV infusion over 3 hrs days 1, 2, 3 Mod B, courses II & VI

Other Name: ara-C

Drug: daunorubicin hydrochloride

80 mg/sq m/day slow IV infusion days 1, 2, 3 Mod A Courses I & V 60 mg/sq m/day slow IV infusion days 1, 2, 3 Mod B Courses II & VI

Drug: dexamethasone

5 mg/sq m PO bid days 1-7 and for pts < = 60y/o days 15-21 Mod A, Course I and days 1-7 for Course V 0.1% eye drops 2 drops qid & prn ea eye days 1-4 Mod B courses II & VI 6 mg/sq m PO days 1-5 of ea maintenance cycle (Course VIII)

Drug: imatinib mesylate

For PH+ patients only:

400 mg PO/day d 15 or later- d 28 Mod A, Courses I & V; d 1-28 Mod B, courses II & VI, and d 1-42 Mod C courses III & VII 600 mg/day PO d 1 of month 1 maintenance until protocol tx is completed

Drug: leucovorin calcium

25 mg/sq m IV push 6 hrs post last MTX Mod C courses III & VII on days 2,16,30 10 mg PO q 6 hrs for 8 doses or until serum MTX < 0.05 uM starting 12 hrs after last IV dose

Drug: mercaptopurine

60 mg/sq m per day days 1-35 Mod C courses III & VII and during maintenance

Drug: methotrexate

Intrathecal 15 mg d 1 Mod B Courses II & VI & d 1,15,29 Mod C courses III & VII IV 1000 mg/sq m d 1,15,29 Mod C courses III & VII PO 25 mg/sq m q 6 hrs 4 doses (starting 6 h post IV MTX) on days 1,2,15,16,29,30 Mod C courses III & VII; PO 20mg/sq m d 1,8,15,22 of ea maintenance cycle

Drug: vincristine sulfate

2 mg IV push d 1,8,15,22 Mod A courses I & V d 1, 15, 29 Mod C courses III & VII d 1 ea maintenance cycle

Drug: Allopurinol

300 mg PO days 1-14 Mod A Course I

Show Detailed Description

Eligibility

Ages Eligible for Study:	15 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed precursor B- or T-lymphoblastic leukemia, L1 or L2 acute lymphoblastic leukemia (ALL), or acute undifferentiated leukemia
No Burkitt-type ALL
No prior treatment for leukemia except for any of the following:
- Emergency leukapheresis
- Emergency treatment for hyperleukocytosis with hydroxyurea
- Cranial radiotherapy for CNS leukostasis (1 dose only)
Must have a pretreatment bone marrow or peripheral blood sample submitted for central immunophenotyping
- Only patients who express CD52 at least 10% in the leukemic blast cell channel are eligible to receive alemtuzumab during module D, course IV

PATIENT CHARACTERISTICS:

Age

15 and over

Performance status

Not specified

Life expectancy

Not specified

Hematopoietic

Not specified

Hepatic

Not specified

Renal

Not specified

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for at least 6 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Disease Characteristics

Chemotherapy

See Disease Characteristics
No other concurrent chemotherapy

Endocrine therapy

Not specified

Radiotherapy

See Disease Characteristics
No concurrent palliative radiotherapy
- Concurrent whole brain radiotherapy allowed for documented CNS disease

Surgery

Not specified

Other

No concurrent alcoholic beverages
No concurrent over-the-counter pain relievers

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00061945

Show 35 Study Locations

Sponsors and Collaborators

Cancer and Leukemia Group B

National Cancer Institute (NCI)

Investigators

Study Chair:

Wendy Stock, MD

University of Chicago

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Stock W, Sanford B, Lozanski G, et al.: Alemtuzumab can be incorporated Into front-line therapy of adult acute lymphoblastic leukemia (ALL): final pase I results of a Cancer and Leukemia Group B study (CALGB 10102). [Abstract] Blood 114 (22): A-838, 2009.

Lozanski G, Sanford B, Mrozek K, et al.: Quantitative measurement of CD52 expression and alemtuzumab binding in adult acute lymphoblastic leukemia (ALL): correlation with immunophenotype and cytogenetics in patients (pts) enrolled on a phase I/II trial from the Cancer and Leukemia Group B (CALGB 10102). [Abstract] Blood 110 (11): A-2386, 2007.

Stock W, Yu D, Sanford B, et al.: Incorporation of alemtuzumab into front-line therapy of adult acute lymphoblastic leukemia (ALL) is feasible: a phase I/II study from the Cancer and Leukemia Group B (CALGB 10102). [Abstract] Blood 106 (11): A-145, 2005.

Responsible Party:	Monica M Bertagnolli, MD, Cancer and Leukemia Group B
ClinicalTrials.gov Identifier:	NCT00061945 History of Changes
Other Study ID Numbers:	CDR0000302482, U10CA031946, CALGB-10102
Study First Received:	June 5, 2003
Last Updated:	April 20, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Cancer and Leukemia Group B:

B-cell adult acute lymphoblastic leukemia
L1 adult acute lymphoblastic leukemia
L2 adult acute lymphoblastic leukemia

T-cell adult acute lymphoblastic leukemia
untreated adult acute lymphoblastic leukemia
acute undifferentiated leukemia

Additional relevant MeSH terms:

Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
6-Mercaptopurine
Allopurinol
Cytarabine
Methotrexate
Cyclophosphamide
Campath 1G

Alemtuzumab
Imatinib
Asparaginase
Daunorubicin
Dexamethasone
Vincristine
BB 1101
Lenograstim
Antibodies, Neoplasm
Dexamethasone acetate
Dexamethasone 21-phosphate
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 12, 2012