Therapy for Pediatric Relapsed or Refractory Precursor B-Cell Acute Lymphoblastic Leukemia and Lymphoma
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ClinicalTrials.gov Identifier: NCT01700946 |
Recruitment Status :
Active, not recruiting
First Posted : October 4, 2012
Last Update Posted : July 21, 2020
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The overall objective of this protocol is to improve the cure rate of relapsed precursor B-cell acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma.
This phase II trial is studying risk-directed therapy for B-lymphoblastic leukemia or lymphoma in first relapse. Standard risk (SR) and high risk (HR) participants will receive different therapy. Treatment will consist of chemotherapy for SR participants, and chemotherapy followed by hematopoietic stem cell transplant (HSCT) for HR in first relapse. Induction therapy consists of three blocks of chemotherapy. The first block is a novel immunotherapy regimen that includes chemotherapy, rituximab and infusion of haploidentical natural killer (NK) cells. SR participants will continue to receive chemotherapy for a total duration of approximately 2 years. HR participants will be candidates for HSCT and will proceed to transplant once a suitable donor is found and their minimal residual disease (MRD) is negative.
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Recurrent B-Cell Childhood Acute Lymphoblastic Leukemia Recurrent Childhood B-Lymphoblastic Lymphoma | Drug: dexamethasone Drug: vincristine sulfate Biological: rituximab Drug: clofarabine Drug: cyclophosphamide Drug: etoposide Biological: aldesleukin Drug: pegaspargase Drug: methotrexate Drug: mercaptopurine Drug: cytarabine Drug: mitoxantrone Drug: teniposide Drug: vinblastine Biological: natural killer cell infusion Other: laboratory biomarker analysis Drug: therapeutic hydrocortisone Procedure: allogeneic hematopoietic stem cell transplantation Device: CliniMACS | Phase 2 |

Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 94 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase II Study of Therapy for Pediatric Relapsed or Refractory Precursor B-Cell Acute Lymphoblastic Leukemia and Lymphoma |
Actual Study Start Date : | April 15, 2013 |
Estimated Primary Completion Date : | April 2021 |
Estimated Study Completion Date : | April 2021 |

Arm | Intervention/treatment |
---|---|
Active Comparator: Standard Risk
Interventions: dexamethasone, vincristine sulfate, rituximab, clofarabine, cyclophosphamide, etoposide, aldesleukin, pegaspargase, methotrexate, mercaptopurine, cytarabine, mitoxantrone, teniposide, vinblastine, natural killer cell infusion, laboratory biomarker analysis, therapeutic hydrocortisone Cells for infusion are prepared using the CliniMACS System. |
Drug: dexamethasone
given intravenously or orally
Other Name: Decadron(R) Drug: vincristine sulfate given intravenously
Other Name: Oncovin(R) Biological: rituximab given intravenously
Other Name: Rituxan(R) Drug: clofarabine given intravenously
Other Names:
Drug: cyclophosphamide given intravenously
Other Name: Cytoxan(R) Drug: etoposide given intravenously
Other Names:
Biological: aldesleukin given subcutaneously
Other Names:
Drug: pegaspargase given intravenously
Other Names:
Drug: methotrexate given intrathecally or intravenously
Other Names:
Drug: mercaptopurine given orally
Other Names:
Drug: cytarabine given intrathecally or intravenously
Other Names:
Drug: mitoxantrone given intravenously
Other Name: Novantrone(R) Drug: teniposide given intravenously
Other Names:
Drug: vinblastine given intravenously
Other Name: Velban(R) Biological: natural killer cell infusion undergo allogeneic natural killer cell infusion
Other Name: NK cell infusion Other: laboratory biomarker analysis correlative studies Drug: therapeutic hydrocortisone given intrathecally
Other Name: Cortef Device: CliniMACS The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.
Other Name: Cell Selection System |
Active Comparator: High Risk
Interventions: dexamethasone, vincristine, rituximab, clofarabine, cyclophosphamide, etoposide, aldesleukin, pegaspargase, methotrexate, mercaptopurine, cytarabine, mitoxantrone, natural killer cell infusion, allogeneic hematopoietic stem cell transplantation, laboratory biomarker analysis, therapeutic hydrocortisone Cells for infusion are prepared using the CliniMACS System. |
Drug: dexamethasone
given intravenously or orally
Other Name: Decadron(R) Drug: vincristine sulfate given intravenously
Other Name: Oncovin(R) Biological: rituximab given intravenously
Other Name: Rituxan(R) Drug: clofarabine given intravenously
Other Names:
Drug: cyclophosphamide given intravenously
Other Name: Cytoxan(R) Drug: etoposide given intravenously
Other Names:
Biological: aldesleukin given subcutaneously
Other Names:
Drug: pegaspargase given intravenously
Other Names:
Drug: methotrexate given intrathecally or intravenously
Other Names:
Drug: mercaptopurine given orally
Other Names:
Drug: cytarabine given intrathecally or intravenously
Other Names:
Drug: mitoxantrone given intravenously
Other Name: Novantrone(R) Biological: natural killer cell infusion undergo allogeneic natural killer cell infusion
Other Name: NK cell infusion Other: laboratory biomarker analysis correlative studies Drug: therapeutic hydrocortisone given intrathecally
Other Name: Cortef Procedure: allogeneic hematopoietic stem cell transplantation undergo allogeneic HSCT
Other Name: HSCT Device: CliniMACS The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.
Other Name: Cell Selection System |
- 3-year overall survival rate of patients with relapsed ALL [ Time Frame: At 3 years of follow-up since the on-study date of the last enrolled patient ]Estimate the 3-year survival rate of participants with first relapse or primary refractory precursor B-cell ALL treated with risk-directed therapy.
- 3-year event-free survival rates in patients with relapsed ALL [ Time Frame: At 3 years of follow-up since the on-study date of the last enrolled patient ]Estimate the 3-year event-free survival rate of participants with first relapse or primary refractory precursor B-cell ALL treated with risk-directed therapy.
- Proportion of participants with positive minimal residual disease [ Time Frame: At 3 months after the on-study date of the last enrolled patient ]To determine minimal residual disease (MRD) levels at the end of remission induction therapy for participants with relapsed precursor B-cell ALL and compare the results with those in protocol ALLR17.
- Mean of CD20 expression levels [ Time Frame: approximately 5 weeks after the on-study date of the last enrolled patient ]To estimate mean levels of CD20 expression at baseline, during treatment with dexamethasone-containing chemotherapy and following rituximab treatment in Block 1 of remission induction therapy for relapsed precursor B-cell ALL.
- Median CD20 expression levels [ Time Frame: approximately 5 weeks after the on-study date of the last enrolled patient ]To estimate median levels of CD20 expression at baseline, during treatment with dexamethasone-containing chemotherapy and following rituximab treatment in Block 1 of remission induction therapy for relapsed precursor B-cell ALL.

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Ages Eligible for Study: | up to 21 Years (Child, Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
INCLUSION CRITERIA:
- Must have relapsed or refractory precursor B-cell acute lymphoblastic leukemia or acute lymphoblastic lymphoma.
-
Participants with leukemia must meet one of the following:
- In first hematologic relapse, defined as the reappearance (in a patient who has previously achieved remission) of leukemia blasts in the bone marrow or peripheral blood, OR
- Refractory to one or two courses of frontline induction therapy (≥ 5% blasts in the bone marrow or peripheral blood confirmed by flow cytometric analysis).
-
Participant with lymphoma must meet one of the following:
- In first relapse, OR
-
Refractory to one or two courses of frontline induction therapy with measurable disease
- Should flow cytometric analyses suggest relapse (by the reappearance of a similar immunophenotype to the original leukemia) in the presence of <5% blasts morphologically, a repeat bone marrow test is recommended to confirm relapse.
- Molecular or genetic relapse is characterized by the reappearance of a cytogenetic or molecular abnormality.
- Early relapse is defined as relapse on therapy or < 6 months after completion of frontline therapy. Late relapse is defined as relapse occurring ≥ 6 months after completion of frontline therapy.
- Participant's age is < 22 years at time of enrollment (e.g. participant is eligible until 22nd birthday).
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Prior therapy:
- There is no waiting period for participants who relapse while receiving frontline therapy and are free from side effects attributable to such therapy.
- Emergent radiation therapy, one dose of intrathecal chemotherapy, and up to 7 days of steroids for treatment of relapse are permitted before start of treatment in participants who relapse after completion of frontline therapy.
- At least 90 days have elapsed since bone marrow transplant and participant is off immune suppression for a minimum of 2 weeks, if applicable. Participants with ALL or NHL who were transplanted in first remission are eligible for this study.
Organ function requirements
- Hepatic: Total bilirubin ≤ upper limit of normal (ULN) for age, or if total bilirubin is > ULN, direct bilirubin ≤ 1.4 mg/dl
- Cardiac: Shortening fraction ≥ 28%
-
Renal: Glomerular filtration rate >50cc/min/1.73 m^2, OR maximum serum creatinine (SC) based on age as follows:
- If age is 1 to 2 years, then maximum SC is 0.6 mg/dL
- If age is 2 to 6 years, then maximum SC is 0.8 mg/dL
- If age is 6 to 10 years, then maximum SC is 1 mg/dL
- If age is 10 to <13 years, then maximum SC is 1.2 mg/dL
- If age is 13 to 16 years, then maximum SC is 1.5 mg/dL for males and 1.4 mg/dL for females
- If age is >16 years, then maximum SC is 1.7 mg/dL for males and 1.4 mg/dL for females
EXCLUSION CRITERIA:
- Leukemia participants ages 1 to 5 years with induction failure AND favorable cytogenetics (i.e., hyperdiploidy defined as DNA index ≥1.16 or modal chromosome number ≥51, or ETV6-RUNXI).
- Hepatitis B or HIV infection.
- Pregnant or breast-feeding
- Inability or unwillingness or research participant or legal guardian/representative to give written informed consent.
INCLUSION CRITERIA FOR NK CELL DONORS:
- Donor is at least 18 years of age.
- Donor is a family member.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01700946
United States, California | |
Rady Children's Hospital and Health Center | |
San Diego, California, United States, 92123 | |
United States, Tennessee | |
St. Jude Children's Research Hospital | |
Memphis, Tennessee, United States, 38105 | |
United States, Texas | |
Cook Children's Medical Center | |
Fort Worth, Texas, United States, 76104 |
Principal Investigator: | Sima Jeha, MD | St. Jude Children's Research Hospital |
Responsible Party: | St. Jude Children's Research Hospital |
ClinicalTrials.gov Identifier: | NCT01700946 |
Other Study ID Numbers: |
ALLR18 NCI-2012-00587 ( Registry Identifier: NCi Clinical Trial Registration Program ) |
First Posted: | October 4, 2012 Key Record Dates |
Last Update Posted: | July 21, 2020 |
Last Verified: | July 2020 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | Yes |
Device Product Not Approved or Cleared by U.S. FDA: | Yes |
leukemia lymphoma Non-Hodgkins |
Lymphoma Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Cytarabine Aldesleukin Dexamethasone Hydrocortisone Hydrocortisone 17-butyrate 21-propionate |
Hydrocortisone acetate Hydrocortisone hemisuccinate Cyclophosphamide Rituximab Methotrexate Etoposide Vincristine Interleukin-2 Asparaginase Mercaptopurine Mitoxantrone Clofarabine Vinblastine Pegaspargase Teniposide |