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Gemtuzumab Ozogamicin and High-Dose Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00006265
First received: September 11, 2000
Last updated: September 27, 2013
Last verified: September 2013
  Purpose

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

PURPOSE: Phase II trial to study the effectiveness of combining gemtuzumab ozogamicin with high-dose cytarabine in treating patients who have relapsed or refractory acute myeloid leukemia.


Condition Intervention Phase
Leukemia
Drug: ara-C
Biological: gemtuzumab ozogamicin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Dose Escalation And Phase II Study Of Gemtuzumab Ozogamicin (CMA-676; Mylotarg) With High-Dose Cytarabine For Patients With Refractory Or Relapsed Acute Myeloid Leukemia (AML)

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Complete remission rate [ Time Frame: 8 or 14 days after tx initiation & 30 d post tx ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity [ Time Frame: D 14, then 30, 60 , & 90 d post Tx, q 3 mon for 1 yr, then at relapse or death ] [ Designated as safety issue: Yes ]

Enrollment: 60
Study Start Date: March 2001
Study Completion Date: May 2005
Primary Completion Date: December 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort I
Immunotherapy with gemtuzumab
Biological: gemtuzumab ozogamicin
9 mg/sq m IV infusion over 2 hrs D 1 (Cohort I); D 7 (Cohorts II, IA, & IV); & D 14 (Cohort IV) 4.5 mg/sq m IV infusion over 2 hrs D 8 (Cohort I) & D 14 (Cohort II)
Other Name: Mylotarg
Experimental: Cohort II
Gemtuzumab + ara-C
Drug: ara-C
3 g/sq m IV infusion over 3 hours Days 1-5
Other Name: Cytarabine
Biological: gemtuzumab ozogamicin
9 mg/sq m IV infusion over 2 hrs D 1 (Cohort I); D 7 (Cohorts II, IA, & IV); & D 14 (Cohort IV) 4.5 mg/sq m IV infusion over 2 hrs D 8 (Cohort I) & D 14 (Cohort II)
Other Name: Mylotarg
Experimental: Cohort IA
Gemtuzumab + ara C
Drug: ara-C
3 g/sq m IV infusion over 3 hours Days 1-5
Other Name: Cytarabine
Biological: gemtuzumab ozogamicin
9 mg/sq m IV infusion over 2 hrs D 1 (Cohort I); D 7 (Cohorts II, IA, & IV); & D 14 (Cohort IV) 4.5 mg/sq m IV infusion over 2 hrs D 8 (Cohort I) & D 14 (Cohort II)
Other Name: Mylotarg
Experimental: Cohort IV
Gemtuzumab + ara-C
Drug: ara-C
3 g/sq m IV infusion over 3 hours Days 1-5
Other Name: Cytarabine
Biological: gemtuzumab ozogamicin
9 mg/sq m IV infusion over 2 hrs D 1 (Cohort I); D 7 (Cohorts II, IA, & IV); & D 14 (Cohort IV) 4.5 mg/sq m IV infusion over 2 hrs D 8 (Cohort I) & D 14 (Cohort II)
Other Name: Mylotarg

Detailed Description:

OBJECTIVES:

  • Determine the response rate in patients with relapsed or refractory acute myeloid leukemia treated with gemtuzumab ozogamicin (CMA-676) and high-dose cytarabine.
  • Determine the safety and toxicity of this regimen in these patients.

OUTLINE: This is a dose-escalation study of gemtuzumab ozogamicin (CMA-676) (phase I closed to accrual effective 08/25/2003). Patients are stratified according to disease status (refractory vs relapsed).

  • Phase I (closed to accrual effective 08/25/2003): Patients are enrolled in one of four cohorts.

    • Cohort I (closed to accrual as of 10/1/02): Patients receive CMA-676 at the first dose level IV over 2 hours on days 1 and 8.
    • Cohort IA (open to accrual as of 10/15/02): Patients receive high-dose cytarabine (HD-ARA-C) IV over 3 hours on days 1-5 and CMA-676 IV over 2 hours on day 7.
    • Cohort II: Patients receive HD-ARA-C as in cohort IA and CMA-676 at the first dose level IV over 2 hours on days 7 and 14.
    • Cohort IV: Patients receive CMA-676 at the second dose level and HD-ARA-C as in cohort II.

Dose escalation stops if at least 3 of 9 patients experience dose-limiting toxicity.

  • Phase II: Patients receive HD-ARA-C IV over 3 hours on days 1-5 and CMA-676 IV over 2 hours on day 7 (one course).

Patients are followed at 1 month, monthly for 6 months, every 3 months for 2 years, and then annually for 10 years.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for phase I of the study and a total of 37 patients will be accrued for phase II of the study within 2 years. (Phase I closed to accrual effective 08/25/2003).

  Eligibility

Ages Eligible for Study:   17 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • One of the following diagnoses:

    • Primary refractory acute myeloid leukemia (AML)

      • More than 10% blasts in the bone marrow or blood after recovery from 2 courses of standard cytarabine- and anthracycline-based induction chemotherapy
      • No prior remission
    • Relapsed AML

      • More than 10% blasts in the bone marrow or blood after documented remission
      • Prior remission lasted more than 30 days
      • No prior treatment for current relapse
  • CD33 expression on at least 20% of leukemia blast cells at initial diagnosis for primary refractory patients or at the time of relapse for all other patients
  • No active CNS involvement

PATIENT CHARACTERISTICS:

Age:

  • 17 and over

Performance status:

  • 0-2

Life expectancy:

  • Not specified

Hematopoietic:

  • See Disease Characteristics
  • WBC less than 30,000/mm^3

Hepatic:

  • Bilirubin less than 2.0 mg/dL
  • No veno-occlusive disease of the liver
  • No chronic liver disease unless due to AML

Renal:

  • Not specified

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No active serious infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • At least 6 months since prior stem cell transplantation

Chemotherapy:

  • See Disease Characteristics
  • Prior etoposide and/or thioguanine during remission induction allowed
  • Prior hydroxyurea for control of AML allowed
  • At least 24 hours since prior hydroxyurea
  • At least 3 months since prior high-dose cytarabine (greater than 2 g/m^2/dose)-containing regimen
  • No other concurrent chemotherapy

Endocrine therapy:

  • Concurrent steroids for adrenal failure, hypersensitivity reactions, or septic shock allowed
  • Concurrent ophthalmic corticosteroids allowed
  • Concurrent hormones for nondisease-related conditions (e.g., insulin for diabetes or estrogens or progestins for gynecologic conditions) allowed

Radiotherapy:

  • No concurrent radiotherapy

Surgery:

  • Not specified

Other:

  • More than 2 months since prior cytotoxic therapy
  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: NCT00006265

  Show 78 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
Investigators
Study Chair: Richard M. Stone, MD Dana-Farber Cancer Institute
  More Information

Additional Information:
Publications:
Stone RM, Moser B, Schulman P, et al.: A dose escalation and phase II study of gemtuzumab ozogamicin (GO) with high-dose cytarabine (HiDAC) for patients (pts) with refractory or relapsed acute myeloid leukemia (AML): CALGB 19902. [Abstract] Blood 104 (11): A-873, 2004.

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00006265     History of Changes
Other Study ID Numbers: CDR0000068208, U10CA031946, CALGB-19902
Study First Received: September 11, 2000
Last Updated: September 27, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Alliance for Clinical Trials in Oncology:
recurrent adult acute myeloid leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms
Neoplasms by Histologic Type
Cytarabine
Gemtuzumab
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014