Alemtuzumab and Combination Chemotherapy in Treating Patients With Untreated Acute Lymphoblastic Leukemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00061945
First received: June 5, 2003
Last updated: March 20, 2014
Last verified: December 2013
  Purpose

This phase I/II trial studies the side effects and best dose of alemtuzumab when given together with combination chemotherapy and to see how well it works in treating patients with untreated acute lymphoblastic leukemia. Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy also work in different ways to kill cancer cells or stop them from growing. Giving alemtuzumab together with combination chemotherapy may be a better way to block cancer growth.


Condition Intervention Phase
Acute Undifferentiated Leukemia
B-cell Adult Acute Lymphoblastic Leukemia
B-cell Childhood Acute Lymphoblastic Leukemia
L1 Adult Acute Lymphoblastic Leukemia
L1 Childhood Acute Lymphoblastic Leukemia
L2 Adult Acute Lymphoblastic Leukemia
L2 Childhood Acute Lymphoblastic Leukemia
Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia
Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia
Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia
T-cell Adult Acute Lymphoblastic Leukemia
T-cell Childhood Acute Lymphoblastic Leukemia
Untreated Adult Acute Lymphoblastic Leukemia
Untreated Childhood Acute Lymphoblastic Leukemia
Drug: allopurinol
Drug: cyclophosphamide
Drug: daunorubicin hydrochloride
Drug: vincristine sulfate
Drug: dexamethasone
Drug: asparaginase
Biological: filgrastim
Drug: imatinib mesylate
Drug: methotrexate
Drug: cytarabine
Drug: trimethoprim-sulfamethoxazole
Drug: mercaptopurine
Drug: leucovorin calcium
Biological: alemtuzumab
Drug: acyclovir
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1
Phase 2

Study Type: Interventional
Study Design: 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:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Alemtuzumab (Phase I) [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    The maximum tolerated dose is defined as the highest alemtuzumab dose at which less than 40% of patients develop the dose limiting toxicity (DLT), where DLT is defined as the inability to proceed (due to medical complications) with the protocol treatment within six weeks of receiving the last dose of alemtuzumab. Groups of six patients will be enrolled into each cohort at the time of re-registration prior to starting Course IV. After a cohort has accrued 6 patients and at least 3 have completed the 2-6 week post alemtuzumab observation period without DLT, the incoming patients will be assigned to the next cohort in the table while the DLT and other toxicities continue to be assessed for the newly closed cohort. If less than 3 out of 6 enrolled patients in a cohort have completed the 2-6 week post alemtuzumab observation period without DLT, additional patients may continue to enroll in that same cohort, i.e., accrual will not be suspended while waiting for patient follow-up data.

  • Number of Participants Who Proceed to Course V Within 2-6 Weeks of the Last Dose of Alemtuzumab (Phase II) [ Time Frame: 8 months ] [ Designated as safety issue: No ]
    The primary endpoint is the number of participants who are able to proceed to course V within two - six weeks of completion of course IV.


Secondary Outcome Measures:
  • Modulation of Minimal Residual Disease During Treatment With Alemtuzumab (Phase II) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • Disease-free Survival (Phase II) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Will be estimated using the Kaplan-Meier method with confidence intervals presented.

  • Overall Survival (Phase II) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Will be estimated using the Kaplan-Meier method with confidence intervals presented.


Enrollment: 302
Study Start Date: June 2003
Study Completion Date: October 2012
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (alemtuzumab and combination chemotherapy)
See detailed description.
Drug: allopurinol
Given PO
Drug: cyclophosphamide
Given IV
Drug: daunorubicin hydrochloride
Given IV
Drug: vincristine sulfate
Given IV
Drug: dexamethasone
Given PO and as eye drops
Drug: asparaginase
Given SC
Biological: filgrastim
Given SC
Drug: imatinib mesylate
Given PO
Drug: methotrexate
Given IT, IV, and PO
Drug: cytarabine
Given IV
Drug: trimethoprim-sulfamethoxazole
Given PO
Drug: mercaptopurine
Given PO
Drug: leucovorin calcium
Given IV and PO
Biological: alemtuzumab
Given SC
Drug: acyclovir
Given PO
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • Unequivocal histologic diagnosis of precursor B or precursor T lymphoblastic leukemia (World Health Organization [WHO] classification), L1 or L2 ALL or acute undifferentiated leukemia (AUL) (French-American-British Cooperative group [FAB] Classification); Burkitt-type ALL (FAB L3, surface immunoglobulin [SIg]+) are excluded
  • No prior treatment for leukemia with three permissible exceptions:

    • Emergency leukapheresis II. Emergency treatment for hyperleukocytosis with hydroxyurea III. Cranial radiation therapy (RT) for central nervous system (CNS) leukostasis (one dose only)
  • All patients must have a pre-treatment bone marrow or peripheral blood sample submitted for central immunophenotyping; only those patients who express CD52 >= 10% in the leukemia blast cell channel will be eligible to receive Campath-1H during module D, course IV
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Illinois
Cancer and Leukemia Group B
Chicago, Illinois, United States, 60606
Sponsors and Collaborators
Investigators
Principal Investigator: Wendy Stock Cancer and Leukemia Group B
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00061945     History of Changes
Other Study ID Numbers: NCI-2012-02807, NCI-2012-02807, CDR302482, CALGB 10102, CALGB-10102, U10CA031946
Study First Received: June 5, 2003
Results First Received: December 5, 2013
Last Updated: March 20, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Philadelphia Chromosome
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Translocation, Genetic
Chromosome Aberrations
Pathologic Processes
Leukemia, Myeloid
6-Mercaptopurine
Allopurinol
Cytarabine
Methotrexate
Cyclophosphamide
Campath 1G
Alemtuzumab
Imatinib
Asparaginase
Daunorubicin
Dexamethasone
Vincristine
BB 1101
Trimethoprim
Lenograstim

ClinicalTrials.gov processed this record on July 24, 2014