Treatment of Older Adults With Acute Lymphoblastic Leukemia

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00973752
• Collaborator: Dana-Farber Cancer Institute (Other), Beth Israel Deaconess Medical Center (Other), Enzon Pharmaceuticals, Inc. (Industry), Genzyme, a Sanofi Company (Industry)
• Enrollment: 30
• Locations: 3
• Arm: 1
• Duration (Months): 80
• Patients Per Site: 10
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the safety and effectiveness of a multi-drug regimen (which includes prednisone, vincristine, cytarabine, doxorubicin, 6 mercaptopurine, and methotrexate) which is considered standard treatment for children and young adults with acute lymphoblastic leukemia (ALL), in combination with PEG-asparaginase and clofarabine to treat older adults with ALL. PEG-asparaginase has been used in chemotherapy treatment regimens for both children and adults with ALL. Clofarabine has been used in chemotherapy treatment regimens for children with ALL and has been shown to decrease the number of leukemia cells. Participants with leukemia that has an abnormal chromosome, called the Philadelphia chromosome, will also be given imatinib.

Condition or Disease	Intervention/Treatment	Phase
Acute Lymphoblastic Leukemia	Drug: Prednisone; Drug: Vincristine; Drug: Doxorubicin; Drug: PEG-asparaginase; Drug: Cytarabine; Drug: Methotrexate; Drug: Imatinib; Drug: Clofarabine; Drug: 6 Mercaptopurine	Phase 2

Detailed Description

• This research study has stages of treatment as follows: 1) Induction 2) Consolidation 1

1. Stem cell of Bone Marrow Transplant (if the participant is eligible). If the participant does not have a transplant: 4) CNS Therapy 5) Consolidation 2 6) Continuation Therapy.

• During all phases of study treatment, participants will have additional tests and procedures to monitor their health and for research purposes. These tests will include: physical exams, blood tests, bone marrow aspirate/biopsy and EKGs (electrocardiogram) and/or ECHOs (echo-cardiogram).

• INDUCTION STAGE: This stage lasts for about one month. The study drugs and the way they are administered are as follows: Prednisone orally on days 1-21 for participants less than 60 and days 1-7 for participants 60 or greater; Vincristine intravenously on days 1, 8, 15 and 22; Doxorubicin intravenously on days 1 and 2; PEG-Asparaginase intravenously on days 7 and 21; Cytarabine intrathecally on day 1; Methotrexate intrathecally on day 29; Imatinib orally on days 14-29 if participant has the Philadelphia Chromosome.

• After induction, if there is evidence of ALL in the spinal fluid, participants may need to receive more intrathecal therapy.

• CONSOLIDATION 1 Therapy: This stage will last about one month. Participants will receive Consolidation 1 Therapy, regardless of whether or not their ALL is in full remission after Induction. The study drugs and the way they are administered are as follows: Prednisone orally days 1-5; Clofarabine intravenously days 1-5; PEG-Asparaginase intravenously days 1 and 15; Imatinib continues orally for participants with the Philadelphia Chromosome.

• After the participants blood counts return to normal, their bone marrow will be tested. If the bone marrow shows remission, participants will proceed to the next stage of the study. If the bone marrow does not show remission, the participants will no longer continue on this study.

• STEM CELL or BONE MARROW TRANSPLANTATION: The next stage is stem cell or bone marrow transplantation if the participant is eligible. If the participant receives a stem cell transplant, they will receive additional chemotherapy (separate from the study drugs) followed by an infusion of stem cells. If the participant receives a bone marrow transplant, they will have a bone marrow aspirate and biopsy 3 months after the transplant and 12 months from the start fo the induction to monitor the status of the ALL. If the participant receives a bone marrow or stem cell transplant, they will continue to be a part of the study, but will not proceed with CNS Therapy, Consolidation 2 Therapy, and Continuation Therapy.

• CENTRAL NERVOUS SYSTEM (CNS) THERAPY: CNS therapy will begin between 2 and 6 weeks following the end of Consolidation 1. This stage will last about one month. The study drugs and the way they are administered are as follows: vincristine intravenously on day 1; doxorubicin intravenously on day 1; 6 mercaptopurine orally on days 1-14; prednisone orally on days 1-5; PEG-asparaginase intravenously on days 1 and 15; methotrexate/cytarabine/prednisone intrathecally weekly for 3 weeks; imatinib orally continues daily if the participant has the Philadelphia Chromosome.

• Radiation therapy will also be given during this stage of the participant is under 60 years old. The purpose of radiation therapy is to prevent ALL from coming back in the brain. Radiation will be given in 8 treatments, given once a day, and will be scheduled with other study treatment.

• CONSOLIDATION 2 THERAPY: This stage begins as soon as CNS Therapy ends and lasts about 8 months. Participants will receive repeated cycles of the study drug treatment about every 4 weeks. The study drugs and the way they are administered are as follows: vincristine intravenously on day 1; doxorubicin intravenously on day 1; 6 mercaptopurine orally on days 1-14; prednisone orally days 1-5; PEG-asparaginase orally on days 1 and 15 (first cycle only); imatinib orally continues daily if the participant has Philadelphia chromosome.

• CONTINUATION THERAPY: This stage begins at the end of Consolidation 2 Therapy. The goal of this stage is to get rid of all of the ALL in the body. Participants will receive repeated cycles of the study drug treatment every 4 weeks. It will last until the participant has been in remission for 2 years. The study drugs and the way they are administered are as follows: vincristine intravenously on day 1; mercaptopurine orally on days 1-14; prednisone orally on days 1-5; methotrexate intravenously on day 15; imatinib orally continues daily if the participant has Philadelphia chromosome.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Treatment of Older Adults With Acute Lymphoblastic Leukemia
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Apr 1, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Experimental All patients treated on same arm

Drug: Prednisone; Orally during Induction, Consolidation 1, CNS, Consolidation 2, and Continuation therapy.; Drug: Vincristine; Intravenously during Induction, CNS, Consolidation 2 and Continuation Therapy; Drug: Doxorubicin; Intravenously during Induction, CNS, and Consolidation 2 therapy; Drug: PEG-asparaginase; Intravenously during Induction, Consolidation 1, CNS, and Consolidation 2 therapy; Drug: Cytarabine; Intrathecally during Induction and CNS therapy; Drug: Methotrexate; Intrathecally during Induction, CNS, and Continuation Therapy; Drug: Imatinib; Orally during Induction, Consolidation 1, CNS, Consolidation 2 and Continuation Therapy; Drug: Clofarabine; Intravenously during Consolidation 1 Therapy; Drug: 6 Mercaptopurine; Orally during CNS, Consolidation 2 and Continuation Therapy

Outcome Measures

Primary Outcome Measures

1. Overall Survival at One Year [1 years]

   The number of participants alive one year after baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 51 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Acute lymphoblastic leukemia, excluding known mature B-cell ALL by the presence of any of the following: surface immunoglobulin, L3 morphology, t(8;14)(q24;q32), t(8;22), or t(2;8).

• Patients with mature B-cell ALL will be removed from the protocol as soon as the diagnosis is made and should be treated on a B-cell leukemia protocol.

• Patients with lymphoblastic lymphoma are also eligible

• No prior anti-leukemic therapy except <1 week of steroids, and/or emergent radiation therapy to the mediastinum, or hydroxyurea or emergent leukopheresis. Longer steroid use for diseases other than leukemia is permitted.

• Age 51-75 years

• Ejection fraction > 45%

• Creatinine < 2.0 mg/dl

• Total bilirubin < 3.0 mg/dl

• ECOG (Eastern Cooperative Oncology Group) Performance Status of 0, 1, 2

• Non-pregnant and non lactating

Exclusion Criteria:

• Known HIV positive

• Comorbid medical condition, in the investigator's opinion, would make participation in this trial and adherence to the protocol guidelines difficult

• Active psychiatric or mental illness making informed consent or careful clinical follow-up unlikely

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02115
3	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Massachusetts General Hospital
• Dana-Farber Cancer Institute
• Beth Israel Deaconess Medical Center
• Enzon Pharmaceuticals, Inc.
• Genzyme, a Sanofi Company

Investigators

• Principal Investigator: Amir Fathi, MD, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Amir Fathi, Principal Investigator, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00973752
• Other Study ID Numbers: 08-356
• First Posted: Sep 9, 2009
• Last Update Posted: Mar 30, 2017
• Last Verified: Feb 1, 2017

• Keywords provided by Amir Fathi, Principal Investigator, Massachusetts General Hospital: ALL
• Additional relevant MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Cytarabine; Prednisone; Doxorubicin; Methotrexate; Vincristine; Asparaginase; Mercaptopurine; Clofarabine; Pegaspargase

Study Results

Participant Flow

Arm/Group Title	Experimental
Arm/Group Description	All patients treated on same arm Prednisone: Orally during Induction, Consolidation 1, CNS (central nervous system), Consolidation 2, and Continuation therapy. Vincristine: Intravenously during Induction, CNS, Consolidation 2 and Continuation Therapy Doxorubicin: Intravenously during Induction, CNS, and Consolidation 2 therapy PEG-asparaginase: Intravenously during Induction, Consolidation 1, CNS, and Consolidation 2 therapy Cytarabine: Intrathecally during Induction and CNS therapy Methotrexate: Intrathecally during Induction, CNS, and Continuation Therapy Imatinib: Orally during Induction, Consolidation 1, CNS, Consolidation 2 and Continuation Therapy Clofarabine: Intravenously during Consolidation 1 Therapy 6 Mercaptopurine: Orally during CNS, Consolidation 2 and Continuation Therapy
Period Title: Overall Study
STARTED	30
COMPLETED	30
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Experimental
Arm/Group Description	All patients treated on same arm Prednisone: Orally during Induction, Consolidation 1, CNS, Consolidation 2, and Continuation therapy. Vincristine: Intravenously during Induction, CNS, Consolidation 2 and Continuation Therapy Doxorubicin: Intravenously during Induction, CNS, and Consolidation 2 therapy PEG-asparaginase: Intravenously during Induction, Consolidation 1, CNS, and Consolidation 2 therapy Cytarabine: Intrathecally during Induction and CNS therapy Methotrexate: Intrathecally during Induction, CNS, and Continuation Therapy Imatinib: Orally during Induction, Consolidation 1, CNS, Consolidation 2 and Continuation Therapy Clofarabine: Intravenously during Consolidation 1 Therapy 6 Mercaptopurine: Orally during CNS, Consolidation 2 and Continuation Therapy
Overall Participants	30
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	58
Sex: Female, Male (Count of Participants)
Female	18 60%
Male	12 40%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	27 90%
Not Available	3 10%
Region of Enrollment (Count of Participants)
United States	30 100%
White blood cell count (10^3 cell per μL) [Median (Full Range) ]
Median (Full Range) [10^3 cell per μL]	10.4
Performance status (Count of Participants)
ECOG 0	14 46.7%
ECOG 1	11 36.7%
ECOG 2	5 16.7%
Chromosomal alterations (Count of Participants)
Philadelphia chromosome positive	12 40%
Mixed lineage leukemia rearrangement	2 6.7%
Immunophenotype (Count of Participants)
B-cell ALL	29 96.7%
T-cell ALL	1 3.3%

Outcome Measures

1. Primary Outcome

Title	Overall Survival at One Year
Description	The number of participants alive one year after baseline.
Time Frame	1 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental
Arm/Group Description	All patients treated on same arm Prednisone: Orally during Induction, Consolidation 1, CNS, Consolidation 2, and Continuation therapy. Vincristine: Intravenously during Induction, CNS, Consolidation 2 and Continuation Therapy Doxorubicin: Intravenously during Induction, CNS, and Consolidation 2 therapy PEG-asparaginase: Intravenously during Induction, Consolidation 1, CNS, and Consolidation 2 therapy Cytarabine: Intrathecally during Induction and CNS therapy Methotrexate: Intrathecally during Induction, CNS, and Continuation Therapy Imatinib: Orally during Induction, Consolidation 1, CNS, Consolidation 2 and Continuation Therapy Clofarabine: Intravenously during Consolidation 1 Therapy 6 Mercaptopurine: Orally during CNS, Consolidation 2 and Continuation Therapy
Measure Participants	30
Count of Participants [Participants]	19 63.3%

Adverse Events

Arm/Group Title	Experimental
Arm/Group Description	All patients treated on same arm Prednisone: Orally during Induction, Consolidation 1, CNS, Consolidation 2, and Continuation therapy. Vincristine: Intravenously during Induction, CNS, Consolidation 2 and Continuation Therapy Doxorubicin: Intravenously during Induction, CNS, and Consolidation 2 therapy PEG-asparaginase: Intravenously during Induction, Consolidation 1, CNS, and Consolidation 2 therapy Cytarabine: Intrathecally during Induction and CNS therapy Methotrexate: Intrathecally during Induction, CNS, and Continuation Therapy Imatinib: Orally during Induction, Consolidation 1, CNS, Consolidation 2 and Continuation Therapy Clofarabine: Intravenously during Consolidation 1 Therapy 6 Mercaptopurine: Orally during CNS, Consolidation 2 and Continuation Therapy
All Cause Mortality
	Experimental
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Experimental
	Affected / at Risk (%)	# Events
Total	10/30 (33.3%)
Gastrointestinal disorders
stomatitis	1/30 (3.3%)
Gastrointestinal bleeding	2/30 (6.7%)
General disorders
Tumor lysis syndrome	2/30 (6.7%)
Hepatobiliary disorders
Transaminitis	7/30 (23.3%)
Hyperbilirubinemia	10/30 (33.3%)
Immune system disorders
Allergic Reaction	3/30 (10%)
Infections and infestations
Infection w/ gr. 3/4 neutropenia	7/30 (23.3%)
Infection - other	3/30 (10%)
Metabolism and nutrition disorders
Hyperglycemia	7/30 (23.3%)
Nervous system disorders
Neuropathy	1/30 (3.3%)
Renal and urinary disorders
Azotemia	1/30 (3.3%)
Other (Not Including Serious) Adverse Events
	Experimental
	Affected / at Risk (%)	# Events
Total	18/30 (60%)
Blood and lymphatic system disorders
Grade 2 Anemia	12/30 (40%)
Cardiac disorders
Grade 2 Hypertension	1/30 (3.3%)
Grade 2 hypotension	6/30 (20%)
Gastrointestinal disorders
Grade 2 anorexia	4/30 (13.3%)
Grade 2 colitis	2/30 (6.7%)
Grade 2 constipation	3/30 (10%)
Grade 2 diarrhea	4/30 (13.3%)
Grade 2 stomatitis	4/30 (13.3%)
Grade 2 nausea	11/30 (36.7%)
Grade 2 taste alteration	1/30 (3.3%)
Grade 2 vomiting	4/30 (13.3%)
Grade 2 Abdominal pain	5/30 (16.7%)
General disorders
Grade 2 fatigue	18/30 (60%)
Grade 2 Insomnia	2/30 (6.7%)
Grade 2 weight loss	1/30 (3.3%)
Grade 2 Edema	9/30 (30%)
Grade 2 hypoalbuminemia	4/30 (13.3%)
Grade 2 weakness	4/30 (13.3%)
Grade 2 mental status change	3/30 (10%)
Grade 2 back pain	2/30 (6.7%)
Grade 2 pain, other	3/30 (10%)
Hepatobiliary disorders
Grade 2 transaminitis	7/30 (23.3%)
Grade 2 Elevated alkaline phosphatase	2/30 (6.7%)
Grade 2 Hyperbilirubinemia	3/30 (10%)
Immune system disorders
Grade 2 Allergic reaction	1/30 (3.3%)
Infections and infestations
Grade 2 febrile neutropenia	4/30 (13.3%)
Grade 2 Infection	9/30 (30%)
Metabolism and nutrition disorders
Grade 2 hyperglycemia	3/30 (10%)
Grade 2 hypocalcemia	4/30 (13.3%)
Nervous system disorders
Grade 2 neuropathy	1/30 (3.3%)
Renal and urinary disorders
Grade 2 azotemia	3/30 (10%)
Grade 2 ureteral obstruction	1/30 (3.3%)
Respiratory, thoracic and mediastinal disorders
Grade 2 dyspnea	1/30 (3.3%)
Grade 2 hypoxia	1/30 (3.3%)
Skin and subcutaneous tissue disorders
Grade 2 erythema multiforme	1/30 (3.3%)
Grade 2 pruritis	1/30 (3.3%)
Grade 2 rash	1/30 (3.3%)
Grade 2 decubitus ulcer	1/30 (3.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.