CMC-544 and Allogeneic Transplantation for CD22 Positive-Lymphoid Malignancies
This study is currently recruiting participants.
Verified April 2013 by M.D. Anderson Cancer Center
Sponsor:
M.D. Anderson Cancer Center
Collaborator:
Pfizer
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01664910
First received: August 10, 2012
Last updated: April 19, 2013
Last verified: April 2013
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Purpose
The goal of this clinical research study is to learn which dose level of inotuzumab ozogamicin (CMC-544) work best when given with fludarabine and bendamustine, with or without rituximab, before a stem cell transplant.The safety of this treatment will also be studied.
Fludarabine, bendamustine, and rituximab are commonly given before stem cell transplants. These drugs are designed to kill cancerous cells and suppress your immune system in order to lower the risk of stem cell transplant rejection.
Inotuzumab ozogamicin is designed to kill cancerous cells and reduce the risk of the cancer coming back.
| Condition | Intervention | Phase |
|---|---|---|
|
Lymphoma Leukemia |
Drug: CMC-544 Drug: Fludarabine Drug: Bendamustine Drug: Rituximab Procedure: Allogeneic Stem Cell Transplantation Drug: Thymoglobulin Drug: Tacrolimus Drug: Methotrexate Drug: G-CSF |
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: | Anti-CD22 Immunoconjugate Inotuzumab Ozogamicin (CMC-544) Added to Fludarabine, Bendamustine and Rituximab and Allogeneic Transplantation for CD22 Positive-Lymphoid Malignancies |
Resource links provided by NLM:
Drug Information available for:
Methotrexate
Bendamustine hydrochloride
Methotrexate sodium
Bendamustine
Fludarabine
Fludarabine phosphate
Tacrolimus
Filgrastim
Lenograstim
Granulocyte colony-stimulating factor
Rituximab
Antilymphocyte Serum
U.S. FDA Resources
Further study details as provided by M.D. Anderson Cancer Center:
Primary Outcome Measures:
- Maximum Tolerated Dose (MTD) of Inotuzumab Ozogamicin (CMC-544) [ Time Frame: 1 months ] [ Designated as safety issue: Yes ]Study design developed by Ji, Li, and Bekele (2007) used to determine maximum tolerated dose (MTD) of CMC-544 targeting a toxicity rate not greater than 30% using a prior beta(0.5, 0.5). MTD defined as the highest dose for which the probability of toxicity is closest to 30%.
Secondary Outcome Measures:
- Overall Survival [ Time Frame: 3 months ] [ Designated as safety issue: No ]Objective overall response estimated (complete response and partial response) with a 95% confidence interval in dose that is declared MTD. Logistic regression used to assess association between response and disease and clinical characteristics of interest. Kaplan-Meier survival curves used to estimate overall survival and recurrence-free survival. Cox proportional hazards regression methodology used to assess association between disease and clinical characteristics and survival outcomes.
| Estimated Enrollment: | 30 |
| Study Start Date: | October 2012 |
| Estimated Primary Completion Date: | October 2017 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Inotuzumab Ozogamicin (CMC-544) + Chemotherapy
D-13, CMC-544 infused intravenously (IV) on Day -13. Starting dose per cohort: 0.6,1.2 or 1.8 mg/m2. Dose based on actual body weight. Fludarabine 30 mg/m2 IV followed by Bendamustine 130 mg/m2 IV on Days -5 to -3. Patients with CD20+ disease also receive Rituximab IV at 375 mg/m2 on Days -6, +1 and +8. Allogeneic stem cell transplantation on Day 0. Thymoglobulin 1 mg/kg administrated IV on Days -2 and -1 to patients receiving a matched unrelated donor (MUD). Tacrolimus on Day -2 administered at starting dose of 0.015 mg/kg (ideal body weight) as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml. Tacrolimus is changed to oral dosing when tolerated and can be tapered off after day +90 if no GVHD is present.
|
Drug: CMC-544
0.6, 1.2 or 1.8 mg/m2 (dose is based on actual body weight) by vein on Day -13.
Other Name: Inotuzumab Ozogamicin
Drug: Fludarabine
30 mg/m2 by vein on Days -5, -4 and -3.
Other Names:
Drug: Bendamustine
130 mg/m2 by vein on Days -5, -4 and -3.
Other Names:
Drug: Rituximab
375 mg/m2 by vein (based on actual body weight) on Day -6, Day +1 and +8 for patients with CD20+ disease.
Other Name: Rituxan
Procedure: Allogeneic Stem Cell Transplantation
Allogeneic stem cell transplantation on Day 0.
Drug: Thymoglobulin
1 mg/kg (based on actual body weight) by vein patients receiving a matched unrelated donor (MUD) on Days -2 and -1.
Other Names:
Drug: Tacrolimus
0.015 mg/kg (ideal body weight) as a 24 hour continuous infusion on Day -2, daily adjusted to achieve a therapeutic level of 5-15 ng/ml. Tacrolimus is changed to oral dosing when tolerated and can be tapered off after Day +90 if no graft versus host disease (GVHD) is present.
Other Name: Prograf
Drug: Methotrexate
5 mg/m2 by vein on Days +1, +3, and +6 for all patients. Patients receiving an unrelated graft will also be given Methotrexate on Day +11 after the transplant.
Drug: G-CSF
5 mcg/kg/day subcutaneously beginning on Day +7 for patients receiving related and MUD. G-CSF will continue until the absolute neutrophil count (ANC) is > 500 x 10/L for 3 consecutive days.
Other Names:
|
Show Detailed Description Eligibility| Ages Eligible for Study: | 18 Years to 70 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Age 18 to 70 years of age.
- Patients with B-cell hematological malignancies who are eligible for allogeneic transplantation.
- Patients must have a fully-matched sibling donor or a matched unrelated donor identified.
- Performance score of at least 80% by Karnofsky or 0 to 2 ECOG.
- Left ventricular EF >/= 45% with no uncontrolled arrhythmias or symptomatic heart disease.
- FEV1, FVC >/= 50% and corrected DLCO >/= 50%.
- Serum creatinine <1.6 mg/dL. Serum bilirubin < 2 mg/dL upper limit of normal (unless due to Gilbert's Disease; patient with this disease should have a right upper quadrant ultrasound evaluation before treatment).
- SGPT < 2 X upper limit of normal.
- Men and women of reproductive potential must agree to follow accepted birth control methods (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
- Negative Beta HCG test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization) or currently breast-feeding. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
Exclusion Criteria:
- Patient with active CNS involvement.
- Known infection with HIV, HTLV-I, Hepatitis B, or Hepatitis C.
- Patients with other malignancies diagnosed within 2 years prior to study registration. Skin squamous or basal cell carcinoma are exceptions.
- Active bacterial, viral or fungal infections.
- History of stroke within 6 months.
- History of biliary colic attack.
- A prior autologous or allogeneic stem cell transplant.
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- Patient has received other investigational drugs within 3 weeks before study registration.
- Serious nonmalignant disease which, in the opinion of the investigator would compromise protocol objectives.
- Prior exposure to CMC-544 within past 6 months.
- Established refractoriness to CMC-544.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01664910
Contacts
| Contact: Issa F. Khouri, MD, BS | 713-792-8750 |
Locations
| United States, Texas | |
| UT MD Anderson Cancer Center | Recruiting |
| Houston, Texas, United States, 77030 | |
Sponsors and Collaborators
M.D. Anderson Cancer Center
Pfizer
Investigators
| Principal Investigator: | Issa F. Khouri, MD, BS | UT MD Anderson Cancer Center |
More Information
Additional Information:
No publications provided
| Responsible Party: | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT01664910 History of Changes |
| Other Study ID Numbers: | 2012-0265 |
| Study First Received: | August 10, 2012 |
| Last Updated: | April 19, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by M.D. Anderson Cancer Center:
|
Lymphoma CD22 Positive-Lymphoid Malignancies Leukemia Allogeneic stem cell transplant CMC-544 Inotuzumab Ozogamicin Fludarabine Fludarabine Phosphate Fludara Bendamustine Bendamustine Hydrochloride Bendamustine HCL CEP-18083 |
SDX105 Treanda G-CSF Filgrastim Neupogen Methotrexate Rituximab Rituxan Thymoglobulin ATG Antithymocyte Globulin Tacrolimus Prograf |
Additional relevant MeSH terms:
|
Neoplasms Leukemia Lymphoma Neoplasms by Histologic Type Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Antilymphocyte Serum Methotrexate Fludarabine monophosphate Tacrolimus Lenograstim Rituximab Vidarabine |
Bendamustine Fludarabine Nitrogen Mustard Compounds Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Abortifacient Agents, Nonsteroidal Abortifacient Agents Reproductive Control Agents Therapeutic Uses Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents |
ClinicalTrials.gov processed this record on May 21, 2013