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Clofarabine, Melphalan, and Thiotepa Followed By a Donor Stem Cell Transplant in Treating Patients With High-Risk and/or Advanced Hematologic Cancer or Other Disease

NCT ID: NCT00423514

Last Updated: 2022-12-27

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

38 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-11-20

Study Completion Date

2021-06-18

Brief Summary

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RATIONALE: Giving chemotherapy, such as clofarabine, melphalan, and thiotepa, before a donor stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and mycophenolate mofetil before the transplant may stop this from happening.

PURPOSE: This phase I/II trial is studying the side effects and best dose of clofarabine when given together with melphalan and thiotepa, followed by a donor stem cell transplant and to see how well it works in treating patients with high-risk and/or advanced hematologic cancer or other disease.

Detailed Description

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OBJECTIVES:

Primary

* Determine the maximum tolerated dose of clofarabine when administered with melphalan and thiotepa followed by allogeneic stem cell transplantation in patients with high-risk and/or advanced hematologic malignancies. (Phase I)
* Determine the 1-year disease-free survival of patients treated with this regimen. (Phase II)
* Determine the efficacy of this regimen, in terms of antileukemic potential and relapse rate, in these patients.

Secondary

* Evaluate the incidence and severity of nonhematologic toxicity of this regimen in these patients.
* Evaluate the incidence and severity of graft-versus-host disease in patients treated with this regimen.

OUTLINE: This is a phase I, dose-escalation study of clofarabine followed by an open-label, phase II study. Patients are stratified according to HLA-compatible donor type (related vs unrelated).

* Cytoreductive therapy: Patients receive clofarabine IV over 2 hours once daily on days -9 to -5, thiotepa IV over 4 hours on day -4, and melphalan IV over 30 minutes once daily on days -3 and -2.

Cohorts of 3-6 patients receive escalating doses of clofarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

* Graft-versus-host disease (GVHD) prophylaxis: Patients who undergo bone marrow or peripheral blood stem cell transplantation receive tacrolimus IV continuously over 24 hours or orally every 8-12 hours beginning on day -3 and methotrexate IV on days 1, 3, 6, and 11. Patients who undergo UCB transplantation receive tacrolimus IV continuously over 24 hours or orally every 8-12 hours beginning on day -3 and mycophenolate mofetil (MMF) IV or orally 2 or 3 times daily on days -3 to 45 followed by a taper until day 100 (unless there are signs of acute GVHD). Patients who undergo UCB transplantation without GVHD continue tacrolimus for 6 months followed by a taper and discontinued 1 year after transplantation.
* Allogeneic hematopoietic stem cell transplantation (HSCT) or allogeneic umbilical cord blood (UCB) transplantation: Patients undergo allogeneic HSCT (bone marrow or peripheral blood stem cells) or double UCB transplantation on day 0. Patients also receive filgrastim (G-CSF) IV or subcutaneously beginning on day 7 and continuing until blood counts recover.
* Maintenance therapy: Approximately 2 months after transplantation patients with ALL, M4 or M5 AML, and those transplanted with AML in bone marrow relapse receive cytarabine intrathecally (IT) monthly for up to 5 doses. Patients with a history of CNS leukemia receive cytarabine IT once monthly during months 2-12 after HSCT.

After completion of study therapy, patients are followed periodically for at least 4 years.

PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.

Conditions

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Graft Versus Host Disease Leukemia Myelodysplastic Syndromes

Keywords

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graft versus host disease adult acute lymphoblastic leukemia in remission adult acute myeloid leukemia in remission childhood acute lymphoblastic leukemia in remission childhood chronic myelogenous leukemia recurrent childhood acute myeloid leukemia accelerated phase chronic myelogenous leukemia acute undifferentiated leukemia adult acute myeloid leukemia with 11q23 (MLL) abnormalities blastic phase chronic myelogenous leukemia juvenile myelomonocytic leukemia previously treated myelodysplastic syndromes recurrent adult acute lymphoblastic leukemia recurrent adult acute myeloid leukemia relapsing chronic myelogenous leukemia secondary acute myeloid leukemia secondary myelodysplastic syndromes childhood acute myeloid leukemia in remission de novo myelodysplastic syndromes recurrent childhood acute lymphoblastic leukemia chronic phase chronic myelogenous leukemia adult acute myeloid leukemia with inv(16)(p13;q22) adult acute myeloid leukemia with t(15;17)(q22;q12) adult acute myeloid leukemia with t(16;16)(p13;q22) adult acute myeloid leukemia with t(8;21)(q22;q22) childhood myelodysplastic syndromes

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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cytoreduction regimen & stem cell transplant

This is a single arm phase I/II clinical trial to assess efficacy (the antileukemic potential and relapse rate), and safety (peri-transplant morbidity and mortality) of a novel cytoreduction regimen in preparation for allogeneic hematopoietic stem cell transplantation (HSCT).

Group Type EXPERIMENTAL

filgrastim

Intervention Type BIOLOGICAL

clofarabine

Intervention Type DRUG

melphalan

Intervention Type DRUG

mycophenolate mofetil

Intervention Type DRUG

tacrolimus

Intervention Type DRUG

thiotepa

Intervention Type DRUG

allogeneic bone marrow transplantation

Intervention Type PROCEDURE

allogeneic hematopoietic stem cell transplantation

Intervention Type PROCEDURE

peripheral blood stem cell transplantation

Intervention Type PROCEDURE

Interventions

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filgrastim

Intervention Type BIOLOGICAL

clofarabine

Intervention Type DRUG

melphalan

Intervention Type DRUG

mycophenolate mofetil

Intervention Type DRUG

tacrolimus

Intervention Type DRUG

thiotepa

Intervention Type DRUG

allogeneic bone marrow transplantation

Intervention Type PROCEDURE

allogeneic hematopoietic stem cell transplantation

Intervention Type PROCEDURE

peripheral blood stem cell transplantation

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* No active uncontrolled viral, bacterial, or fungal infection
* No known HIV I or II positivity
* No known human T-cell lymphotrophic virus I or II positivity
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

* No hydroxyurea within the past 2 weeks
* No allogeneic or autologous stem cell transplantation within the past 6 months
Minimum Eligible Age

0 Years

Maximum Eligible Age

54 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Farid Boulad, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

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Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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http://www.mskcc.org/mskcc/html/44.cfm

Memorial Sloan Kettering Cancer Center

Other Identifiers

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MSKCC-06125

Identifier Type: -

Identifier Source: secondary_id

06-125

Identifier Type: -

Identifier Source: org_study_id