Phase 1 Study of Combotox With Cytarabine in Relapsed/Refractory B-lineage Acute Lymphoblastic Leukemia (ALL)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2012 by Montefiore Medical Center
University of Texas Southwestern Medical Center
Information provided by (Responsible Party):
Montefiore Medical Center Identifier:
First received: July 12, 2011
Last updated: November 8, 2012
Last verified: November 2012

This study will test different doses of combotox in your disease to find out what dose of this drug can be given safely to patients. Combotox will be given with cytarabine. You might have been given cytarabine as part of your treatment for ALL before; even if you have received cytarabine before, it usually still works when it is given if the leukemia has not completely disappeared with the first treatment (or is "refractory") or if the leukemia has come back (or has "relapsed"). Another purpose of this study is to find out what effects (good and bad) the experimental drug Combotox has on you and your disease (ALL) when combined with cytarabine.

Condition Intervention Phase
B-cell Adult Acute Lymphoblastic Leukemia
Acute Lymphoblastic Leukemia
Drug: Combotox
Drug: Cytarabine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study of the Deglycosylated Ricin A Chain-containing Combined Anti-CD19 and Anti-CD22 Immunotoxin Combotox in Combination With High-dose Cytarabine in Adult Relapsed or Refractory B-lineage Acute Lymphoblastic Leukemia

Resource links provided by NLM:

Further study details as provided by Montefiore Medical Center:

Primary Outcome Measures:
  • Number of Participants with Dose-limiting Toxicity [ Time Frame: approximately one month ] [ Designated as safety issue: Yes ]
    Number of Participants with Dose-limiting Toxicity

Estimated Enrollment: 20
Study Start Date: June 2011
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Therapy Intervention
Combotox will be given with cytarabine
Drug: Combotox
To administer the test dose take 0.2 ml (0.1 mg) of filtered Combotox and combine with 5 ml of normal saline, and administer by IV push. If there are no signs of an allergic reaction by 30 minutes, then the 4-hour infusion may be started.
Other Name: there are no other names
Drug: Cytarabine
2g/m2 IV over 2-3 hours every 12 hours on days 1, 2 and 3. Cycle repeated upon hematopoietic recovery
Other Name: • Cytosar-U®

Detailed Description:

To define the maximum tolerated dose (MTD) of Combotox when added to high-dose cytarabine during salvage therapy for adult patients with relapsed or refractory B-lineage acute lymphoblastic leukemia.

  • To evaluate the efficacy of this regimen
  • To assess for the presence of a postulated CD34+/CD38-/low/CD19+ leukemic stem cell phenotype in the bone marrow at time of relapse and to assess its association with treatment outcome
  • To determine the development of human mouse or Ricin antibodies (HAMA/HARA);
  • To determine the pharmacokinetic characteristics of combotox;
  • To evaluate the value of fractional excretion of sodium (FeNa) as early marker of toxicity.

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

Inclusion Criteria:

  • Must have histologically confirmed B-lineage ALL at diagnosis and either evidence of relapse / refractory disease based on a Bone Marrow / Peripheral Blood examination or evidence by cytogenetic studies or PCR amplification.
  • CD19 and/or CD22 must be expressed on at least 50% of the lymphoblasts
  • Disease must be refractory to conventional induction therapy or relapsed after initial standard therapy for ALL. Any number of prior therapies is permitted and including allogeneic and/or autologous stem cell transplant
  • Age more than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of Combotox in combination with Cytarabine in patients less than 18 years of age, children are excluded from this study, but will be eligible for future pediatric phase 1 combination trials.
  • ECOG performance status less than or equal to 2
  • Life expectancy greater than 2 months
  • Normal organ and marrow function as follows: total bilirubin less than 1.5 X institutional upper limit of normal, unless related to leukemic infiltration or hemolysis; AST(SGOT)/ALT(SGPT) less than 2.5 X institutional upper limit of normal, unless related to leukemic infiltration or hemolysis; Creatinine within normal institutional limits OR Creatinine clearance greater than 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
  • Must have recovered from effects of prior therapy. At least 2 weeks should have elapsed since the last dose of high dose chemotherapy. Hydroxyurea, steroids and vincristine are allowed to control counts until eligibility is confirmed and study treatment can be initiated.
  • Adequate cardiac function defined as an ejection fraction of more than or equal to 50% by MUGA scan or echocardiogram and a QTc interval of less than or equal to 450ms for men and less than or equal to 460ms for women
  • Adequate pulmonary function defined as no evidence of dyspnea at rest.
  • Use of adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier.
  • (4 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier.
  • May not be receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to combotox or other agents used in study agents
  • Presence of significant pleural effusion by chest x-ray
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic
  • Presence of active untreated CNS leukemia
  • Presence of GVHD more than grade 2
  • History of documented seizure disorder, presence of cerebellar dysfunction, dysphasia or altered mental status on neurological examination
  • Human anti-mouse antibody (HAMA) levels of 100μg/ml or human ricin antibodies (HARA) > 100μg/ml HARA after cycle 1
  • Impaired liver function defined as a total bilirubin greater than 1.5 x normal range and AST or ALT greater than 2.5 x normal range unless secondary to Gilbert's disease, hemolysis or leukemic involvement of the liver
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study
  • HIV-positive patients on combination antiretroviral therapy are ineligible
  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 identifier: NCT01408160

Contact: Stefan Barta, MD 718-920-4826
Contact: Joseph Zaino 718-920-2006

United States, New York
Montefiore Medical Center Recruiting
Bronx, New York, United States, 10467
Contact: Barta    718-920-4826      
Contact: Zaino    718-920-2006      
Sub-Investigator: Samir Parekh, MD         
Sub-Investigator: Ira Braunschweig, MD         
Sub-Investigator: Amit Verma, MD         
Principal Investigator: Stefan Barta, MD         
Sub-Investigator: Olga Derman, MD         
Sponsors and Collaborators
Montefiore Medical Center
University of Texas Southwestern Medical Center
Study Chair: Stefan Barta, MD Montefiore Medical Center
  More Information

No publications provided by Montefiore Medical Center

Additional publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Montefiore Medical Center Identifier: NCT01408160     History of Changes
Other Study ID Numbers: 11-04-146
Study First Received: July 12, 2011
Last Updated: November 8, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Montefiore Medical Center:
Adult Relapsed B-lineage Acute Lymphoblastic Leukemia
Refractory B-lineage Acute Lymphoblastic Leukemia
Acute Lymphoblastic Leukemia
High-dose Cytarabine
Deglycosylated Ricin A Chain

Additional relevant MeSH terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs processed this record on July 22, 2014