Intensity Modulated Total Marrow Irradiation, Fludarabine Phosphate, and Melphalan in Treating Patients With Relapsed Hematologic Cancers Undergoing a Second Donor Stem Cell Transplant

NCT02333162 | Suspended Phase 1 DMC

• 3 other identifiers: IRB14-0709NCI-2014-02469P30CA014599
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and the best dose of intensity modulated total marrow irradiation (IMTMI) when given together with fludarabine phosphate and melphalan in treating patients with cancers of the blood (hematologic) that have returned after a period of improvement (relapsed) undergoing a second donor stem cell transplant. IMTMI is a type of radiation therapy to the bone marrow that may be less toxic and may also reduce the chances of cancer to return. Giving fludarabine phosphate, melphalan, and IMTMI before a donor stem cell transplant may help stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also 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.

Conditions

Recurrent Hematologic Malignancy; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Previously Treated Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• MTD of conditioning regimen defined as any grade III or higher dose-limiting toxicity, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  Up to 30 days post second allo-SCT

Secondary Outcomes (6)

• Overall incidence of adverse events, graded according to the NCI CTCAE version 4.0

  Up to 2 years

• Transplant related mortality

  Day 100

• Time to neutrophil engraftment

  First day in which the ANC is > 500/mm^3 for 3 consecutive days

• Time to platelet engraftment

  First day the platelet count is > 20,000/mm^3 without transfusion support for 7 consecutive days

• overall survival (OS)

  Up to 2 years

Study Arms (1)

Treatment (IMTMI, combination chemotherapy, PBSCT or BMT)

EXPERIMENTAL

CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes daily on days -7 to -3 and melphalan IV on day -2. Patients also undergo IMTMI BID for 2 to 5 days between days -7 to -3. TRANSPLANT: Patients undergo allogeneic PBSCT or BMT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously over 24 hours or PO BID on days -2 to 180 with taper thereafter and mycophenolate mofetil IV every 8 hours or PO on days 0-28 (for matched donors) or days 0-40 (for alternative donors) with taper to day 60.

Drug: Fludarabine Phosphate; Drug: Melphalan; Radiation: Intensity-Modulated Radiation Therapy; Radiation: Total Marrow Irradiation; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Procedure: Peripheral Blood Stem Cell Transplantation; Procedure: Allogeneic Bone Marrow Transplantation; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Other: Laboratory Biomarker Analysis

Interventions

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, SH T 586

Treatment (IMTMI, combination chemotherapy, PBSCT or BMT)

Melphalan DRUG

Given IV

Also known as: Alkeran

Treatment (IMTMI, combination chemotherapy, PBSCT or BMT)

Intensity-Modulated Radiation Therapy RADIATION

Undergo IMTMI

Also known as: IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy

Treatment (IMTMI, combination chemotherapy, PBSCT or BMT)

Total Marrow Irradiation RADIATION

Undergo IMTMI

Treatment (IMTMI, combination chemotherapy, PBSCT or BMT)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo allogeneic PBSCT

Also known as: PBPC transplantation, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplantation

Treatment (IMTMI, combination chemotherapy, PBSCT or BMT)

Allogeneic Bone Marrow Transplantation PROCEDURE

Undergo allogeneic BMT

Also known as: Allo BMT, Allogeneic BMT

Treatment (IMTMI, combination chemotherapy, PBSCT or BMT)

Tacrolimus DRUG

Given IV or PO

Also known as: Advagraf, FK 506

Treatment (IMTMI, combination chemotherapy, PBSCT or BMT)

Mycophenolate Mofetil DRUG

Given IV or PO

Also known as: Cellcept, MMF

Treatment (IMTMI, combination chemotherapy, PBSCT or BMT)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (IMTMI, combination chemotherapy, PBSCT or BMT)

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo allogeneic PBSCT

Also known as: HSC, HSCT

Treatment (IMTMI, combination chemotherapy, PBSCT or BMT)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with the following diseases: acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS) undergoing second allogeneic (allo)-stem cell transplant (SCT) using the same donor or different donor for disease relapse; patients with other hematologic malignancies, including acute lymphoblastic leukemia (ALL), will be at the discretion of the investigators
• Karnofsky performance status of 70 or above
• Life expectancy is not severely limited by concomitant illness
• Adequate cardiac and pulmonary function; patients with decreased left ventricular ejection fraction (LVEF) =\< 40% or diffusion capacity of carbon monoxide (DLCO) =\< 50% of predicted will be evaluated by cardiology or pulmonary prior to enrollment on this protocol
• Serum creatinine =\<1.5 mg/dL or creatinine clearance \> 50 ml/min; some patients with minor deviations may be accepted on protocol after discussion with the principal investigator (PI)
• Serum bilirubin =\< 2.0 mg/dl; some patients with minor deviations may be accepted on protocol after discussion with the PI
• Serum glutamic oxaloacetic transaminase (SGPT) \< 5 x upper limit of normal; some patients with minor deviations may be accepted on protocol after discussion with the PI
• No evidence of chronic active hepatitis or cirrhosis
• Human immunodeficiency virus (HIV)-negative
• Patient is not pregnant
• Patient or guardian able to sign informed consent
• DONOR: Since these patients already had first allo-SCT; in the majority time, the same matched donor has been used for second allo-SCT; if the patients have multiple donors, alternative matched (8/8 or 10/10) donor could be used for the second allo-SCT; the donor could be matched related donors or matched unrelated donors from registry
• DONOR: If more than one potential volunteer unrelated donor is considered suitable, further selection of the most suitable donor will be prioritized as follows or will follow our institutional guideline from our stem cell transplant standard operating procedure (SOP):
• Age of donor (18-24 \> 25-34 \> 35-44 \> 45+)
• Sex of donor (male \> female, nulliparous female \> parous, multiparous female)

Sponsors & Collaborators

• University of Chicago: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Hematologic Neoplasms

Interventions

fludarabine phosphate; Melphalan; Radiotherapy, Intensity-Modulated; Peripheral Blood Stem Cell Transplantation; Tacrolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Study Officials

• Hongtao Liu

  University of Chicago Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2015
• First Posted: January 7, 2015
• Study Start: December 5, 2014
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: March 30, 2026

Record last verified: 2026-03

Locations

US (1)